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Sample records for renal tubulointerstitial fibrosis

  1. Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: pathological findings on repeat renal biopsy

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    Arai, Haruna; Hayashi, Hiroki; Takahashi, Kazuo; Koide, Shigehisa; Sato, Waichi; Hasegawa, Midori; Yamaguchi, Yutaka; Aten, Jan; Ito, Yasuhiko; Yuzawa, Yukio

    2015-01-01

    Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of

  2. Identification of Tisp40 as an Essential Regulator of Renal Tubulointerstitial Fibrosis via TGF-β/Smads Pathway

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    Cheng-cheng Xiao

    2017-06-01

    Full Text Available Background: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. Methods: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM accumulation, epithelial-mesenchymal transition (EMT and the underlying molecular mechanisms in transforming growth factor-β (TGF-β-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR, Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo. Results: The data showed that Tisp40 was upregulated in a model of renal fibrosis induced by I/R injury (IRI. Upon IRI, Tisp40-deficient mice showed attenuated renal fibrosis compared with wild-type mice. Furthermore, the expression of α-smooth muscle actin, E-cadherin, fibronectin, and collagen I was suppressed. Tisp40 overexpression aggravated ECM accumulation and EMT in the TGF-β-stimulated TCMK-1 cell line, whereas the opposite occurred in cells treated with small interfering RNA (siRNA targeting Tisp40. Importantly, it is changes in the Smad pathway that attenuate renal fibrosis. Conclusion: These findings suggest that Tisp40 plays a critical role in the TGF-β/ Smads pathway involved in this process. Hence, Tisp40 could be a useful therapeutic target in the fight against renal tubulointerstitial fibrosis.

  3. Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

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    Gonzalez, Julien; Mouttalib, Sofia; Delage, Christine; Calise, Denis; Maoret, Jean-Jose; Pradere, Jean-Philippe; Klein, Julie; Buffin-Meyer, Benedicte; Van der Veen, Betty; Charo, Israel F.; Heeringa, Peter; Duchene, Johan; Bascands, Jean-Loup; Schanstra, Joost-Peter

    2013-01-01

    Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can

  4. Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression.

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    Law, Becker M P; Wilkinson, Ray; Wang, Xiangju; Kildey, Katrina; Lindner, Mae; Rist, Melissa J; Beagley, Kenneth; Healy, Helen; Kassianos, Andrew J

    2017-07-01

    Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3 - CD56 + ) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 dim NK cell subset and particularly the CD56 bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 bright NK cells (NKp46 + CD117 + ) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ-producing CD56 bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  5. Lysyl oxidase‑like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis.

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    Choi, Sung-Eun; Jeon, Nara; Choi, Hoon Young; Shin, Jae Il; Jeong, Hyeon Joo; Lim, Beom Jin

    2017-09-01

    Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.

  6. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

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    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  7. Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

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    Bambery Pradeep

    2006-11-01

    Full Text Available Abstract Background Hornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis. Case presentation We describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis. He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids. Conclusion Rare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal function

  8. End-stage Renal Failure as a Complication of Acute Tubulo-Interstitial Nephritis

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    Reda, G.; Ali, R.; Abdelrehman, M.; Sinha, A. K.; Ayman, K.

    2005-01-01

    Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure, where renal impairement tends to be variable but recovery is the rule. End-stage renal failure (ESRF) has been rarely reported as a complication of ATIN. We report here a case of idiopathic ATIN that resulted in severe acute renal failure. The patient developed ESRF, which required permanent renal replacement therapy. (author)

  9. IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

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    Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

    2013-04-01

    Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  10. Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus

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    Minara Shamkhalovna Shamkhalova

    2010-09-01

    patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF, and endothelium-affecting factors (ADMA, homocysteine. Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function. Conclusion. The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.

  11. Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction.

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    Choi, Hoon Young; Lee, Hyun Gyu; Kim, Beom Seok; Ahn, Sun Hee; Jung, Ara; Lee, Mirae; Lee, Jung Eun; Kim, Hyung Jong; Ha, Sung Kyu; Park, Hyeong Cheon

    2015-03-11

    Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo. MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining. KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively. Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.

  12. A mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress

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    Sian E. Piret

    2017-06-01

    Full Text Available Renal fibrosis is a common feature of renal failure resulting from multiple etiologies, including diabetic nephropathy, hypertension and inherited renal disorders. However, the mechanisms of renal fibrosis are incompletely understood and we therefore explored these by establishing a mouse model for a renal tubular disorder, referred to as autosomal dominant tubulointerstitial kidney disease (ADTKD due to missense uromodulin (UMOD mutations (ADTKD-UMOD. ADTKD-UMOD, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R. Heterozygous and homozygous mutant mice developed reduced uric acid excretion, renal fibrosis, immune cell infiltration and progressive renal failure, with decreased maturation and excretion of uromodulin, due to its retention in the ER. The ER stress marker 78 kDa glucose-regulated protein (GRP78 was elevated in cells expressing mutant uromodulin in heterozygous and homozygous mutant mice, and this was accompanied, both in vivo and ex vivo, by upregulation of two unfolded protein response pathways in primary thick ascending limb cells from homozygous mutant mice. However, this did not lead to an increase in apoptosis in vivo. Thus, we have developed a novel mouse model for renal fibrosis, which will be a valuable resource to decipher the mechanisms linking uromodulin mutations with ER stress and renal fibrosis.

  13. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

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    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

  14. Characteristic tubulointerstitial nephritis in IgG4-related disease.

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    Yamaguchi, Yutaka; Kanetsuna, Yukiko; Honda, Kazuho; Yamanaka, Nobuaki; Kawano, Mitsuhiro; Nagata, Michio

    2012-04-01

    Nephropathy associated with IgG4-related disease is characterized by tubulointerstitial nephritis. To better identify its pathology, the present study analyzed clinicopathologic features of IgG4-related tubulointerstitial nephritis cases from across Japan. Sixteen cases were identified as IgG4-related nephropathy using the criterion of high serum IgG4 levels (>135 mg/dL) with abnormal kidney computed tomography or elevated serum creatinine levels. Male predominance (75%) and advanced age (average, 62.0 years) were noted. Eight cases displayed no autoimmune pancreatitis. Renal computed tomography abnormalities were found in 12 of 13 cases examined. Renal dysfunction was found in 15 of 16 cases at biopsy. Distinctive features of tubulointerstitial lesions included (1) well-demarcated borders between involved and uninvolved areas; (2) involvement of the cortex and medulla, often extending beyond the renal capsule and with occasional extension to retroperitoneal fibrosis; (3) interstitial inflammatory cells comprising predominantly plasma cells and lymphocytes, with a high prevalence of IgG4-positive cells often admixed with fibrosis; (4) peculiar features of interstitial fibrosis resembling a "bird's-eye" pattern comprising fibrosis among inter-plasma cell spaces; and (5) deposits visible by light and immunofluorescent microscopy in the tubular basement membrane, Bowman capsule, and interstitium that are restricted to the involved portion, sparing normal parts. Ultrastructural analysis revealed the presence of myofibroblasts with intracellular/pericellular collagen accompanied by plasma cell accumulation from an early stage. Histology could not discriminate between IgG4-related tubulointerstitial nephritis with and without autoimmune pancreatitis. In conclusion, the distinctive histologic features of IgG4-related tubulointerstitial nephritis can facilitate the differential diagnosis of tubulointerstitial nephritis, even without autoimmune pancreatitis or an abnormal

  15. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

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    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  16. Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosis in vivo and in vitro.

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    Liu, Shing-Hwa; Yang, Ching-Chin; Chan, Ding-Cheng; Wu, Cheng-Tien; Chen, Li-Ping; Huang, Jenq-Wen; Hung, Kuan-Yu; Chiang, Chih-Kang

    2016-04-19

    Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stage renal disease. Interesting, endoplasmic reticulum (ER) stress is known to contribute to the pathophysiological mechanisms during the development of renal fibrosis. Here, we investigated the effects of chemical chaperon sodium 4-phenylbutyrate (4-PBA) on renal fibrosis in vivo and in vitro. In a rat unilateral ureteral obstruction (UUO) model, 4-PBA mimicked endogenous ER chaperon in the kidneys and significantly reduced glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), activating transcription factor 4 (ATF4), and phosphorylated JNK protein expressions as well as restored spliced X-box-binding protein 1 (XBP1) expressions in the kidneys of UUO rats. 4-PBA also attenuated the increases of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) protein expressions, tubulointerstitial fibrosis, and apoptosis in the kidneys of UUO rats. Moreover, transforming growth factor (TGF)-β markedly increased ER stress-associated molecules, profibrotic factors, and apoptotic markers in the renal tubular cells (NRK-52E), all of which could be significantly counteracted by 4-PBA treatment. 4-PBA also diminished TGF-β-increased CTGF promoter activity and CTGF mRNA expression in NRK-52E cells. Taken together, our results indicated that 4-PBA acts as an ER chaperone to ameliorate ER stress-induced renal tubular cell apoptosis and renal fibrosis.

  17. Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report

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    Rathi Shradha

    2007-11-01

    Full Text Available Abstract Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca chelation with fatty acids, producing enteric hyperoxaluria. Case A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier (normal 0.6–1.3 mg/dL. Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal Conclusion 1 High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2 The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3 Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.

  18. Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

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    Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

    2017-02-01

    Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

  19. The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury.

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    Jaklien C Leemans

    Full Text Available Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2 is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/- or TLR2(+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/- mice compared with TLR2(+/+ animals. Although, the obstructed kidneys of TLR2(-/- mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.

  20. Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.

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    Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying

    2018-05-01

    Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.

  1. Ketamine induced renal fibrosis in a ketamine addition rat model

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    Mei-Yu Jang

    2017-09-01

    Conclusion: Ketamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.

  2. Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

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    Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

    2017-03-01

    Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

  3. Fanconi's syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs.

    Science.gov (United States)

    Hong, Yin-Tai; Fu, Lin-Shien; Chung, Lin-Huei; Hung, Shien-Chung; Huang, Yi-Ting; Chi, Chin-Shiang

    2006-04-01

    Aristolochic acid-associated nephropathy (AAN) has been identified as a separate entity of progressive tubulo-interstitial nephropathy. Its characteristic pathological findings, including hypocellular interstitial fibrosis, intimal thickening of interlobular and afferent arterioles with glomeruli sparing or mild sclerosis, have been identified. Many cases of AAN in adults have been reported in Taiwan as well as throughout the world, but it has seldom been described in children. We report on a 10-year-old boy who presented with severe anemia, Fanconi's syndrome, and progressive renal failure. Renal biopsy revealed typical findings of AAN. Aristolochic acids I and II were identified from a Chinese herb mixture ingested by the boy. AAN was diagnosed after other etiologies had been excluded. The case demonstrates the hazards of Chinese herbs with regard to children's health in Taiwan and suggests that more attention should be paid to this issue.

  4. L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

    Science.gov (United States)

    Arévalo, Miguel; Núñez-Gómez, Elena; Pérez-Roque, Lucía; Pericacho, Miguel; González-Núñez, María; Langa, Carmen; Martínez-Salgado, Carlos; Perez-Barriocanal, Fernando; Bernabeu, Carmelo; Lopez-Novoa, José M.

    2014-01-01

    Transforming growth factor-β (TGF-β) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-β co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of α-smooth muscle actin (α-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of α-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development. PMID:25313562

  5. Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ-induced diabetic rats: role of Toll-like receptor 2.

    Science.gov (United States)

    Zhang, Wei; Zhao, Li; Su, Shuang-Quan; Xu, Xing-Xin; Wu, Yong-Gui

    2014-01-01

    Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-κB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.

  6. Pentraxin 3 Activates JNK Signaling and Regulates the Epithelial-To-Mesenchymal Transition in Renal Fibrosis

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    Tung-Wei Hung

    2016-12-01

    Full Text Available Background/Aims: Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3 is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2 cells and a rat unilateral ureteral obstruction (UUO model of renal fibrosis. Methods: Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3 on HK-2 cells. Cell proliferation (MTT assay and in vitro cell migration were measured. The levels of PTX3, p-JNK, and EMT markers were measured using immunohistochemistry, RT-PCR, and western blotting in UUO rats and HK-2 cells. Results: HK-2 cells treated with Rh PTX3 did not affect cell viability, but significantly increased cell migration. Moreover, Rh-PTX3 increased the expression of snail, slug, N-cadherin, and vimentin, decreased the expression of E-cadherin, and increased the phosphorylation of JNK. SP600126 (a specific JNK inhibitor enhanced the effects of Rh-PTX3. Rats with UUO exhibited time-dependent increased levels of PTX3, p-JNK, and vimentin, and decreased expression of E-cadherin. Conclusions: Our results suggest that PTX3 induces cell migration via upregulation of EMT in a JNK-dependent mechanism, and highlight the role of PTX3 in the pathogenesis renal fibrosis.

  7. Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    Li, Ao; Zhang, Xiaoxun; Shu, Mao; Wu, Mingjun; Wang, Jun; Zhang, Jingyao; Wang, Rui; Li, Peng; Wang, Yitao

    2017-07-01

    Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats. Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays. Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan. ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative

  8. Renal microvascular disease in an aging population: a reversible process?

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2008-01-01

    Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

  9. Progression of Tubulointerstitial Fibrosis and the Chronic Kidney Disease Phenotype – Role of Risk Factors and Epigenetics

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    Timothy D. Hewitson

    2017-08-01

    Full Text Available Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic kidney disease (CKD in these patients. To explain the heterogeneity of the CKD phenotype requires an understanding of the relevant risk factors for fibrosis. These factors include both the extrinsic nature of injury, and intrinsic factors such as age, gender, genetics, and perpetual activation of fibroblasts through priming. In many cases an additional level of regulation is provided by epigenetic mechanisms which integrate the various pro-fibrotic and anti-fibrotic triggers in fibrogenesis. In this review we therefore examine the various molecular and structural changes of fibrosis, and how they are influenced by extrinsic and intrinsic factors. Our aim is to provide a unifying hypothesis to help explain the transition from acute to CKD.

  10. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

    Science.gov (United States)

    Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

    2017-09-01

    Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

  11. Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

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    Feng Liu

    2016-06-01

    Full Text Available Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

  12. Alpha8 Integrin (Itga8 Signalling Attenuates Chronic Renal Interstitial Fibrosis by Reducing Fibroblast Activation, Not by Interfering with Regulation of Cell Turnover.

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    Ines Marek

    Full Text Available The α8 integrin (Itga8 chain contributes to the regulation of cell proliferation and apoptosis in renal glomerular cells. In unilateral ureteral obstruction Itga8 is de novo expressed in the tubulointerstitium and a deficiency of Itga8 results in more severe renal fibrosis after unilateral ureteral obstruction. We hypothesized that the increased tubulointerstitial damage after unilateral ureteral obstruction observed in mice deficient for Itga8 is associated with altered tubulointerstitial cell turnover and apoptotic mechanisms resulting from the lack of Itga8 in cells of the tubulointerstitium. Induction of unilateral ureteral obstruction was achieved by ligation of the right ureter in mice lacking Itga8. Unilateral ureteral obstruction increased proliferation and apoptosis rates of tubuloepithelial and interstitial cells, however, no differences were observed in the tubulointerstitium of mice lacking Itga8 and wild type controls regarding fibroblast or proliferating cell numbers as well as markers of endoplasmic reticulum stress and apoptosis after unilateral ureteral obstruction. In contrast, unilateral ureteral obstruction in mice lacking Itga8 led to more pronounced tubulointerstitial cell activation i.e. to the appearance of more phospho-SMAD2/3-positive cells and more α-smooth muscle actin-positive cells in the tubulointerstitium. Furthermore, a more severe macrophage and T-cell infiltration was observed in these animals compared to controls. Thus, Itga8 seems to attenuate tubulointerstitial fibrosis in unilateral ureteral obstruction not via regulation of cell turnover, but via regulation of TGF-β signalling, fibroblast activation and/or immune cell infiltration.

  13. Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

    Science.gov (United States)

    Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

    2010-01-01

    The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

  14. TGF-β/Smad signaling in renal fibrosis

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    Xiao-Ming eMeng

    2015-03-01

    Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

  15. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  16. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  17. Nephrogenic systemic fibrosis symptoms alleviated by renal transplantation

    DEFF Research Database (Denmark)

    Hansen, Jesper Melchior

    2011-01-01

    are limited. Anecdotal reports have shown partial or complete resolution of NSF following successful renal transplantation early in the course of NSF. In this report, we describe alleviation of NSF symptoms in two women following successful renal transplantation more than 3 years after onset of NSF.......Nephrogenic systemic fibrosis (NSF) is a rare, serious, and life-threatening disease of patients with severe renal impairment. Gadolinium-containing contrast agents have been shown to be the crucial trigger. There is no proven medical cure for the disease, and symptomatic treatment options...

  18. Immunoglobulin G4-related tubulointerstitial nephritis: A not to be missed diagnosis

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    Smita Mary Matthai

    2017-01-01

    Full Text Available Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN is a newly recognized clinicopathological entity characterized by a dense interstitial infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4-related disease (IgG4-RD which is a novel, immune-mediated, fibroinflammatory and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal involvement in an elderly male patient with poor response to corticosteroid therapy. The distinctive serological, histopathological, and ultrastructural features of this condition which can facilitate differential diagnosis of TIN are highlighted to emphasize the need for early diagnosis and preservation of kidney function.

  19. Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry.

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    Alton B Farris

    Full Text Available Renal tubulointerstitial injury often leads to interstitial fibrosis and tubular atrophy (IF/TA. IF/TA is typically assessed in the renal cortex and can be objectively quantitated with computerized image analysis (IA. However, the human medulla accounts for a substantial proportion of the nephron; therefore, medullary scarring will have important cortical consequences and may parallel overall chronic renal injury. Trichrome, periodic acid-Schiff (PAS, and collagen III immunohistochemistry (IHC were visually examined and quantitated on scanned whole slide images (WSIs (N = 67 cases. When tuned to measure fibrosis, IA of trichrome and Trichrome-PAS (T-P WSIs correlated for all anatomic compartments (among cortex, medulla, and entire tissue, r = 0.84 to 0.89, P all <0.0001; and collagen III deposition correlated between compartments (r = 0.69 to 0.89, P <0.0001 to 0.0002; however, trichrome and T-P measures did not correlate with collagen deposition, suggesting heterogeneous contributions to extracellular matrix deposition. Epithelial cell mass (EPCM correlated between cortex and medulla when measured with cytokeratin IHC and with the trichrome red portion (r = 0.85 and 0.66, respectively, all P < 0.0001. Visual assessment also correlated between compartments for fibrosis and EPCM. Correlations were found between increasing medullary inner stripe (IS width and fibrosis in all of the tissue and the medulla by trichrome morphometry (r = 0.56, P < 0.0001, and r = 0.48, P = 0.00008, respectively. Weak correlations were found between increasing IS width and decreasing visual assessment of all tissue EPCM. Microvessel density (MVD and microvessel area (MVA measured using a MVD algorithm applied to CD34 IHC correlated significantly between all compartments (r = 0.76 to 0.87 for MVD and 0.71 to 0.87 for MVA, P all < 0.0001. Overall, these findings demonstrate the interrelatedness of the cortex and medulla and the importance of considering the renal

  20. Inhibition of IκB Kinase at 24 Hours After Acute Kidney Injury Improves Recovery of Renal Function and Attenuates Fibrosis.

    Science.gov (United States)

    Johnson, Florence L; Patel, Nimesh S A; Purvis, Gareth S D; Chiazza, Fausto; Chen, Jianmin; Sordi, Regina; Hache, Guillaume; Merezhko, Viktoria V; Collino, Massimo; Yaqoob, Muhammed M; Thiemermann, Christoph

    2017-07-03

    Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease. Nuclear factor-κB is a nuclear transcription factor activated post-ischemia, responsible for the transcription of proinflammatory proteins. The role of nuclear factor-κB in the renal fibrosis post-AKI is unknown. We used a rat model of AKI caused by unilateral nephrectomy plus contralateral ischemia (30 minutes) and reperfusion injury (up to 28 days) to show impairment of renal function (peak: 24 hours), activation of nuclear factor-κB (peak: 48 hours), and fibrosis (28 days). In humans, AKI is diagnosed by a rise in serum creatinine. We have discovered that the IκB kinase inhibitor IKK16 (even when given at peak serum creatinine) still improved functional and structural recovery and reduced myofibroblast formation, macrophage infiltration, transforming growth factor-β expression, and Smad2/3 phosphorylation. AKI resulted in fibrosis within 28 days (Sirius red staining, expression of fibronectin), which was abolished by IKK16. To confirm the efficacy of IKK16 in a more severe model of fibrosis, animals were subject to 14 days of unilateral ureteral obstruction, resulting in tubulointerstitial fibrosis, myofibroblast formation, and macrophage infiltration, all of which were attenuated by IKK16. Inhibition of IκB kinase at peak creatinine improves functional recovery, reduces further injury, and prevents fibrosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  1. Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

    Science.gov (United States)

    Evans, B D; Dilwith, R L; Balaban, S L; Rudofsky, U H

    1988-01-01

    Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

  2. Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case report

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    Daumas Aurélie

    2012-04-01

    Full Text Available Abstract Introduction Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease. Case presentation A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically. Conclusions This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.

  3. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    Science.gov (United States)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  4. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

  5. Role of bone morphogenetic protein-7 in renal fibrosis

    Directory of Open Access Journals (Sweden)

    Rui Xi eLi

    2015-04-01

    Full Text Available Renal fibrosis is final common pathway of end stage renal disease. Irrespective of the primary cause, renal fibrogenesis is a dynamic process which involves a large network of cellular and molecular interaction, including pro-inflammatory cell infiltration and activation, matrix-producing cell accumulation and activation, and secretion of profibrogenic factors that modulate extracellular matrix (ECM formation and cell-cell interaction. Bone morphogenetic protein-7 is a protein of the TGF-β super family and increasingly regarded as a counteracting molecule against TGF-β. A large variety of evidence shows an anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely mediated via counterbalancing the profibrotic effect of TGF-β. Besides, BMP-7 reduced ECM formation by inactivating matrix-producing cells and promoting mesenchymal-to-epithelial transition (MET. BMP-7 also increased ECM degradation. Despite these observations, the anti-fibrotic effect of BMP-7 is still controversial such that fine regulation of BMP-7 expression in vivo might be a great challenge for its ultimate clinical application.

  6. Role of bone morphogenetic protein-7 in renal fibrosis

    Science.gov (United States)

    Li, Rui Xi; Yiu, Wai Han; Tang, Sydney C. W.

    2015-01-01

    Renal fibrosis is final common pathway of end stage renal disease. Irrespective of the primary cause, renal fibrogenesis is a dynamic process which involves a large network of cellular and molecular interaction, including pro-inflammatory cell infiltration and activation, matrix-producing cell accumulation and activation, and secretion of profibrogenic factors that modulate extracellular matrix (ECM) formation and cell-cell interaction. Bone morphogenetic protein-7 is a protein of the TGF-β super family and increasingly regarded as a counteracting molecule against TGF-β. A large variety of evidence shows an anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely mediated via counterbalancing the profibrotic effect of TGF-β. Besides, BMP-7 reduced ECM formation by inactivating matrix-producing cells and promoting mesenchymal-to-epithelial transition (MET). BMP-7 also increased ECM degradation. Despite these observations, the anti-fibrotic effect of BMP-7 is still controversial such that fine regulation of BMP-7 expression in vivo might be a great challenge for its ultimate clinical application. PMID:25954203

  7. Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis.

    Science.gov (United States)

    Xu, Guibin; Yue, Fei; Huang, Hai; He, Yongzhong; Li, Xun; Zhao, Haibo; Su, Zhengming; Jiang, Xianhan; Li, Wenjiao; Zou, Jing; Chen, Qi; Liu, Leyuan

    2016-05-01

    Excessive deposition of extracellular matrix proteins in renal tissues causes renal fibrosis and renal function failure. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles. MAP1S is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and predicts a better prognosis in patients suffering from clear cell renal cell carcinomas. Furthermore, we have characterized that MAP1S enhances the turnover of fibronectin, and mice overexpressing LC3 but with MAP1S deleted accumulate fibronectin and develop liver fibrosis because of the synergistic impact of LC3-induced over-synthesis of fibronectin and MAP1S depletion-caused impairment of fibronectin degradation. Here we show that a suppression of MAP1S in renal cells caused an impairment of autophagy clearance of fibronectin and an activation of pyroptosis. Depletion of MAP1S in mice leads to an accumulation of fibrosis-related proteins and the development of renal fibrosis in aged mice. The levels of MAP1S were dramatically reduced and levels of fibronectin were greatly elevated in renal fibrotic tissues from patients diagnosed as renal atrophy and renal failure. Therefore, MAP1S deficiency may cause the accumulation of fibronectin and the development of renal fibrosis.

  8. Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney.

    Science.gov (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui

    2015-01-01

    BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and the expression of BAG3 and α-SMA, and the efficacy of C. sinensis on renal fibrosis induced by UUO were examined. The results showed that UUO led to collagen accumulation, which was significantly suppressed by C. sinensis. UUO increased the expression of BAG3 and α-SMA, a mesenchymal marker, while UUO induced BAG3 and α-SMA expression was significantly inhibited by C. sinensis. In addition, immunohistochemical staining demonstrated that BAG3 immunoreactivity was restricted to tubular epithelium. In conclusion, BAG3 is a potential target for the prevention and/or treatment of renal fibrosis, and C. Sinensis is a promising agent for renal fibrosis.

  9. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    International Nuclear Information System (INIS)

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-01-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and 125 I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion

  10. Magnetization Transfer Magnetic Resonance Imaging Noninvasively Detects Renal Fibrosis in Swine Atherosclerotic Renal Artery Stenosis at 3.0 T.

    Science.gov (United States)

    Jiang, Kai; Ferguson, Christopher M; Woollard, John R; Zhu, Xiangyang; Lerman, Lilach O

    2017-11-01

    Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

  11. Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging.

    Science.gov (United States)

    Chung, Ki Wung; Lee, Eun Kyeong; Lee, Mi Kyung; Oh, Goo Taeg; Yu, Byung Pal; Chung, Hae Young

    2018-04-01

    Defects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator-activated receptor α (PPAR α ) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPAR α and the FAO pathway-associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPAR α protein expression associated with increased expression of PPAR α -targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPAR α expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF- β -induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPAR α -/- mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPAR α signaling during aging aggravates renal fibrosis development, and targeting PPAR α is useful for preventing age-associated CKD. Copyright © 2018 by the American Society of Nephrology.

  12. Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Xiujuan; Hong, Quan; Wang, Zhen; Yu, Yanyan; Zou, Xin; Xu, Lihong

    2016-02-01

    Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-β (TGF-β)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF-β-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-β. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-β by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), α-smooth muscle actin, and fibroblast-specific protein1 in TGF-β-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-β through activation of SphK1. Furthermore, it was observed that TGF-β-stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-β-stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF-β-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis. © 2015 by the Society for Experimental Biology and Medicine.

  13. Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction.

    Science.gov (United States)

    Kato, Noritoshi; Kosugi, Tomoki; Sato, Waichi; Ishimoto, Takuji; Kojima, Hiroshi; Sato, Yuka; Sakamoto, Kazuma; Maruyama, Shoichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji

    2011-02-01

    Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg(-/-)) demonstrated significantly less fibrosis after surgery than Bsg(+/+) mice. Fewer macrophages had infiltrated in Bsg(-/-) kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg(-/-) mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor β. Furthermore, Bsg(-/-) embryonic fibro blasts produced less hyaluronan and α-smooth muscle actin after transforming growth factor β stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Sinomenine attenuates renal fibrosis through Nrf2-mediated inhibition of oxidative stress and TGFβ signaling

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Tian [School of Life Science & Technology, China Pharmaceutical University, Nanjing 210009 (China); Yin, Shasha; Yang, Jun; Zhang, Qin; Liu, Yangyang [Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing 210093 (China); Huang, Fengjie, E-mail: hfj@cpu.edu.cn [School of Life Science & Technology, China Pharmaceutical University, Nanjing 210009 (China); Cao, Wangsen, E-mail: wangsencao@nju.edu.cn [Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing 210093 (China)

    2016-08-01

    Renal fibrosis is the common feature of chronic kidney disease and mainly mediated by TGFβ-associated pro-fibrogenic signaling, which causes excessive extracellular matrix accumulation and successive loss of kidney functions. Sinomenine (SIN), an alkaloid derived from medicinal herb extensively used in treatment of rheumatoid arthritis and various inflammatory disorders, displays renal protective properties in experimental animals; however its pharmacological potency against renal fibrosis is not explored. In this study we report that SIN possesses strong anti-renal fibrosis functions in kidney cell and in mouse fibrotic kidney. SIN beneficially modulated the pro-fibrogenic protein expression in TGFβ-treated kidney cells and attenuated the renal fibrotic pathogenesis incurred by unilateral ureteral obstruction (UUO), which correlated with its activation of Nrf2 signaling - the key defender against oxidative stress with anti-fibrotic potentials. Further investigation on its regulation of Nrf2 downstream events revealed that SIN significantly balanced oxidative stress via improving the expression and activity of anti-oxidant and detoxifying enzymes, and interrupted the pro-fibrogenic signaling of TGFβ/Smad and Wnt/β-catenin. Even more impressively SIN achieved its anti-fibrotic activities in an Nrf2-dependent manner, suggesting that SIN regulation of Nrf2-associated anti-fibrotic activities constitutes a critical component of SIN's renoprotective functions. Collectively our studies have demonstrated a novel anti-fibrotic property of SIN and its upstream events and provided a molecular basis for SIN's potential applications in treatment of renal fibrosis-associated kidney disorders. - Highlights: • Sinomenine has strong potency of inhibiting renal fibrosis in UUO mouse kidney. • Sinomenine attenuates the expression of profibrogenic proteins. • Sinomenine balances renal fibrosis-associated oxidative stress. • Sinomenine mitigates profibrogenic

  15. Idiopathic retroperitoneal fibrosis involving a unilateral renal sinus: A case report and literature review

    International Nuclear Information System (INIS)

    Lee, Seul Bi; Yoon, Jung Hee; Kim, Seung Ho; Lee, Ye Daum; Kim, Suk Jung; Lim, Yun Jung; Jung, Hyun Kyung; Lee, Jin Soo

    2016-01-01

    Idiopathic retroperitoneal fibrosis (RPF) is a rare disease entity and its etiology is uncertain. We report two similar cases which showed an uncommon presentation of idiopathic RPF. A 66-year-old woman and an 80-year-old man presented with incidental findings of left renal pelvic mass-like lesions. Computed tomography revealed a soft tissue density mass replacing the left renal pelvis, which was suspicious for renal pelvic cancer, and the diagnosis of idiopathic RPF was surgically confirmed. To the best of our knowledge, a few cases of idiopathic RPF presenting with features of a localized unilateral renal pelvic mass mimicking renal pelvic cancer have been reported

  16. Idiopathic retroperitoneal fibrosis involving a unilateral renal sinus: A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seul Bi; Yoon, Jung Hee; Kim, Seung Ho; Lee, Ye Daum; Kim, Suk Jung; Lim, Yun Jung; Jung, Hyun Kyung; Lee, Jin Soo [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2016-06-15

    Idiopathic retroperitoneal fibrosis (RPF) is a rare disease entity and its etiology is uncertain. We report two similar cases which showed an uncommon presentation of idiopathic RPF. A 66-year-old woman and an 80-year-old man presented with incidental findings of left renal pelvic mass-like lesions. Computed tomography revealed a soft tissue density mass replacing the left renal pelvis, which was suspicious for renal pelvic cancer, and the diagnosis of idiopathic RPF was surgically confirmed. To the best of our knowledge, a few cases of idiopathic RPF presenting with features of a localized unilateral renal pelvic mass mimicking renal pelvic cancer have been reported.

  17. Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

    Science.gov (United States)

    Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

    2017-09-04

    The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

  18. Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

    Science.gov (United States)

    Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

    2014-01-01

    Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

  19. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  20. Elevated bilirubin levels are associated with a better renal prognosis and ameliorate kidney fibrosis.

    Science.gov (United States)

    Park, Sehoon; Kim, Do Hyoung; Hwang, Jin Ho; Kim, Yong-Chul; Kim, Jin Hyuk; Lim, Chun Soo; Kim, Yon Su; Yang, Seung Hee; Lee, Jung Pyo

    2017-01-01

    Bilirubin has been reported to protect against kidney injury. However, further studies highlighting the beneficial effects of bilirubin on renal fibrosis and chronic renal function decline are necessary. We assessed a prospective cohort with a reference range of total bilirubin levels. The primary outcome was a 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline, and the secondary outcome was a doubling of the serum creatinine levels, halving of the eGFR and the initiation of dialysis. In addition, experiments with tubular epithelial cells and C57BL/6 mice were performed to investigate the protective effects of bilirubin on kidney fibrosis. As a result, 1,080 patients were included in the study cohort. The study group with relative hyperbilirubinemia (total bilirubin 0.8-1.2 mg/dL) showed a better prognosis in terms of the primary outcome (adjusted hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.19-0.59, P bilirubin-treated mice showed less fibrosis in the unilateral ureteral obstruction (UUO) model (P bilirubin treatment decreased fibronectin expression in tubular epithelial cells in a dose-dependent manner (P bilirubin levels were associated with better renal prognosis, and bilirubin treatment induced a beneficial effect on renal fibrosis. Therefore, bilirubin could be a potential therapeutic target to delay fibrosis-related kidney disease progression.

  1. Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

    Science.gov (United States)

    Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

    2014-01-01

    Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

  2. Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Zhao, J.; Wang, Z.J.; Liu, M.; Zhu, J.; Zhang, X.; Zhang, T.; Li, S.; Li, Y.

    2014-01-01

    Aim: To assess the performance of diffusion-weighted magnetic resonance imaging (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with histopathology as a reference standard. Materials and methods: Forty patients with CKD and 30 healthy volunteers were recruited for the study. All participants underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC) values were compared between CKD patients and the healthy volunteers. Pearson's correlation coefficient was calculated to investigate the relationship between ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24h-UPRO), and renal histopathological scores. Results: Cortical and medullary ADC values in the CKD group were significantly lower compared to those in the healthy controls. In the CKD group, a significant negative correlation was found between cortical ADC values and SCr/24h-UPRO, and significant positive correlation was found between cortical ADC and eGFR. There was also a significant negative correlation between medullary ADC values and SCr. Both cortical and medullary ADC values were significantly correlated with histopathological fibrosis score. Conclusion: Renal ADC values strongly correlate with histological measures of fibrosis, and have the potential to enhance the non-invasive monitoring of chronic kidney disease. - Highlights: • Renal ADC values in the CKD patients were lower than those in controls. • Renal ADC values were strongly correlated with histological fibrosis score. • Renal ADC values have the potential to enhance the noninvasive monitoring of CKD

  3. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    Science.gov (United States)

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  4. Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology.

    Science.gov (United States)

    Zhao, Liangcai; Dong, Minjian; Liao, Shixian; Du, Yao; Zhou, Qi; Zheng, Hong; Chen, Minjiang; Ji, Jiansong; Gao, Hongchang

    2016-06-03

    Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases.

  5. New strategy for renal fibrosis: Targeting Smad3 proteins for ubiquitination and degradation.

    Science.gov (United States)

    Wang, Xin; Feng, Shaozhen; Fan, Jinjin; Li, Xiaoyan; Wen, Qiong; Luo, Ning

    2016-09-15

    Smad3 is a critical signaling protein in renal fibrosis. Proteolysis targeting chimeric molecules (PROTACs) are small molecules designed to degrade target proteins via ubiquitination. They have three components: (1) a recognition motif for E3 ligase; (2) a linker; and (3) a ligand for the target protein. We aimed to design a new PROTAC to prevent renal fibrosis by targeting Smad3 proteins and using hydroxylated pentapeptide of hypoxia-inducible factor-1α as the recognition motif for von Hippel-Lindau (VHL) ubiquitin ligase (E3). Computer-aided drug design was used to find a specific ligand targeting Smad3. Surface plasmon resonance (SPR) was used to verify and optimize screening results. Synthesized PROTAC was validated by two-stage mass spectrometry. The PROTAC's specificity for VHL (E3 ligase) was proved with two human renal carcinoma cell lines, 786-0 (VHL(-)) and ACHN (VHL(+)), and its anti-fibrosis effect was tested in renal fibrosis cell models. Thirteen small molecular compounds (SMCs) were obtained from the Enamine library using GLIDE molecular docking program. SPR results showed that #8 SMC (EN300-72284) combined best with Smad3 (KD=4.547×10(-5)M). Mass spectrometry showed that synthesized PROTAC had the correct peptide molecular weights. Western blot showed Smad3 was degraded by PROTAC with whole-cell lysate of ACHN but not 786-0. Degradation, but not ubiquitination, of Smad3 was inhibited by proteasome inhibitor MG132. The upregulation of fibronectin and Collagen I induced by TGF-β1 in both renal fibroblast and mesangial cells were inhibited by PROTAC. The new PROTAC might prevent renal fibrosis by targeting Smad3 for ubiquitination and degradation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; van Goor, Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-gamma is hampered due to inflammation-mediated systemic side effects. We used an interferon-gamma

  7. The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury

    NARCIS (Netherlands)

    Leemans, Jaklien C.; Butter, Loes M.; Pulskens, Wilco P. C.; Teske, Gwendoline J. D.; Claessen, Nike; van der Poll, Tom; Florquin, Sandrine

    2009-01-01

    Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The

  8. The cytoskeleton as a novel target for treatment of renal fibrosis.

    Science.gov (United States)

    Parrish, Alan R

    2016-10-01

    The incidence of chronic kidney disease (CKD) is increasing, with an estimated prevalence of 12% in the United States (Synder et al., 2009). While CKD may progress to end-stage renal disease (ESRD), which necessitates renal replacement therapy, i.e. dialysis or transplantation, most CKD patients never reach ESRD due to the increased risk of death from cardiovascular disease. It is well-established that regardless of the initiating insult - most often diabetes or hypertension - fibrosis is the common pathogenic pathway that leads to progressive injury and organ dysfunction (Eddy, 2014; Duffield, 2014). As such, there has been extensive research into the molecular and cellular mechanisms of renal fibrosis; however, translation to effective therapeutic strategies has been limited. While a role for the disruption of the cytoskeleton, most notably the actin network, has been established in acute kidney injury over the past two decades, a role in regulating renal fibrosis and CKD is only recently emerging. This review will focus on the role of the cytoskeleton in regulating pro-fibrotic pathways in the kidney, as well as data suggesting that these pathways represent novel therapeutic targets to manage fibrosis and ultimately CKD. Copyright © 2016. Published by Elsevier Inc.

  9. Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.

    Science.gov (United States)

    Morinaga, Jun; Kadomatsu, Tsuyoshi; Miyata, Keishi; Endo, Motoyoshi; Terada, Kazutoyo; Tian, Zhe; Sugizaki, Taichi; Tanigawa, Hiroki; Zhao, Jiabin; Zhu, Shunshun; Sato, Michio; Araki, Kimi; Iyama, Ken-ichi; Tomita, Kengo; Mukoyama, Masashi; Tomita, Kimio; Kitamura, Kenichiro; Oike, Yuichi

    2016-02-01

    Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-β1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-β1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney. Thus, ANGPTL2 and TGF-β1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  10. Pharmacokinetics and pharmacodynamics study of rhein treating renal fibrosis based on metabonomics approach.

    Science.gov (United States)

    Sun, Hao; Luo, Guangwen; Xiang, Zheng; Cai, Xiaojun; Chen, Dahui

    2016-12-01

    The selection of effect indicators in the pharmacokinetic/ pharmacodynamic study of complex diseases to describe the relationship between plasma concentration and effect indicators is difficult. Three effect indicators of renal fibrosis were successfully determined. The relationship between pharmacokinetics and pharmacodynamics of rhein in rhubarb was elucidated. The study was a metabolomics analysis of rat plasma and pharmacokinetics/ pharmacodynamics of rhein. A sensitive and simple ultra performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-MS/MS) method was applied to determine the rhein plasma concentration in the rat model of renal fibrosis and rat sham-operated group after the administration of rhubarb decoction. Then, the ultra performance liquid chromatography-Micromass quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) metabolomics method was used to screen biomarkers of renal fibrosis in rat plasma. Furthermore, the relationship between the plasma concentration of rhein and the concentration of three biomarkers directly related to renal fibrosis were analyzed. The three screened biomarkers could represent the effect of rhein treatment on renal fibrosis. Increasing the plasma concentration of rhein tended to restore the concentration of the three biomarkers in the model group compared with that in the sham-operated group. Evident differences in the area under the plasma concentration-time curve (AUC) of rhein were also observed under different pathological states. The results provide valuable information for the clinical application of rhubarb. Rhein intervention could recover the physiological balance in living organisms from the pharmacokinetic/pharmacodynamic levels. New information on the pharmacokinetic/pharmacodynamic study of complex diseases is provided. Copyright © 2016 Elsevier GmbH. All rights reserved.

  11. Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

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    Akito Maeshima

    2014-01-01

    Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

  12. IgG4-Related Tubulointerstitial Nephritis.

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    Zhang, Pingchuan; Cornell, Lynn D

    2017-03-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  13. Cambios morfológicos, celulares y moleculares en la fibrosis renal debido al envejecimiento

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    Miguel Alaga

    2015-11-01

    Full Text Available En los últimos 50 años se ha registrado un aumento gradual de la tasa de envejecimiento de la población uruguaya, reflejándose en un incremento de pacientes con enfermedad renal crónica mayores de 65 años. Este fenómeno plantea la interrogante de cómo el envejecimiento tisular afecta la función del riñón y, en particular cómo contribuye al desarrollo de la fibrosis renal. Con el envejecimiento se producen cambios morfológicos y funcionales en el riñón, tales como la esclerosis glomerular y la fibrosis intersticial. Estos cambios son consecuencia de alteraciones que ocurren a nivel celular. En este trabajo se profundizará en los mecanismos celulares que desencadenan la fibrosis intersticial y la gloméruloesclerosis, describiendo el proceso de inflamación sostenida, la transformación fenotípica de las células epiteliales a miofibroblastos, así como los mecanismos de producción de matriz extracelular y la perpetuación de la fibrosis renal. Además, detallaremos las cascadas moleculares involucradas en el proceso de fibrosis, poniendo énfasis en las cascadas reguladas por TGF-β1 y sus vías de interacción, que regulan la producción factores pro- y anti-fibróticos. También veremos como el TGF-β1 modula la expresión de ARN pequeños no-codificantes (microARNs, potentes inhibidores de la expresión génica, y como el gen anti-envejecimiento Klotho inhibe el avance de la fibrosis renal. Finalmente, discutiremos terapias para frenar o enlentecer el proceso de fibrosis renal, especialmente aquellas que tengan como blanco las cascadas de señalización activadas por TGF-β1, los microRNAs y posibles terapias de activación del gen Klotho para prevenir la progresión de esta patología.

  14. Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

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    Xuejiao Sun

    2017-01-01

    Full Text Available Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E-1,5-bis(2-bromophenyl penta-1,4-dien-3-one(B06 in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1 and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4 as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

  15. Shenqiwan Ameliorates Renal Fibrosis in Rats by Inhibiting TGF-β1/Smads Signaling Pathway

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    Hongshu Chen

    2017-01-01

    Full Text Available Epithelial-mesenchymal transition (EMT refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF. Traditional Chinese Medicine Shenqiwan (SQW is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg was established and intragastrically treated with various concentrations of SQW at dose of 1.5 g/kg, 3 g/kg, and 6 g/kg. Control group and model group were given the same volume of saline. Meanwhile, the positive control group was treated with Enalapril (4 mg/kg. Animals were sacrificed on 21st day after administration. The results showed that SQW could significantly relieve renal pathological damage caused by adenine, increase gene and protein expression of E-cadherin, and decrease the expression of Vimentin in kidney samples. In addition, SQW efficiently inhibited the mRNA and protein expression of p-Smad2/3 by upregulating Smad7. These results suggest that SQW could slow down the progression of renal fibrosis, possibly by inhibiting TGF-β1/Smads signaling pathway.

  16. Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka.

    Science.gov (United States)

    Nanayakkara, Shanika; Komiya, Toshiyuki; Ratnatunga, Neelakanthi; Senevirathna, S T M L D; Harada, Kouji H; Hitomi, Toshiaki; Gobe, Glenda; Muso, Eri; Abeysekera, Tilak; Koizumi, Akio

    2012-05-01

    Chronic kidney disease of uncertain etiology (CKDu) in North Central Province of Sri Lanka has become a key public health concern in the agricultural sector due to the dramatic rise in its prevalence and mortality among young farmers. Although cadmium has been suspected as a causative pathogen, there have been controversies. To date, the pathological characteristics of the disease have not been reported. Histopathological observations of 64 renal biopsies obtained at Anuradhapura General Hospital from October 2008 to July 2009 were scored according to Banff 97 Working Classification of Renal Allograft pathology. The correlations between the histological observations and clinical parameters were statistically analyzed. Interstitial fibrosis and tubular atrophy with or without nonspecific interstitial mononuclear cell infiltration was the dominant histopathological observation. Glomerular sclerosis, glomerular collapse, and features of vascular pathology such as fibrous intimal thickening and arteriolar hyalinosis were also common. Although hypertension was identified as one of the common clinical features among the cases, it did not influence the histopathological lesions in all the cases. This study concludes that tubulointerstitial damage is the major pathological lesion in CKDu. Exposure(s) to an environmental pathogen(s) should be systematically investigated to elucidate such tubulointerstitial damage in CKDu.

  17. Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Pei-Fang [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Shu-Fen [Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan (China); Hung, Tsung-Jen [Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Hung, Chien-Ya [Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Guo-Zheng [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Chuang, Lea-Yea [Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Chen, Mei-Fen [Department of Acupressure Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Wang, Jue-Long [Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan (China); Shi, Ming-Der [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan (China); Hsu, Chen Hung [Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Shiue, Yow-Ling, E-mail: shiue.shirley@gmail.com [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Yang, Yu-Lin, E-mail: Call0955443221@gmail.com [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China)

    2016-11-15

    Background: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods: In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results: Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin

  18. Concurrent IgG4-related tubulointerstitial nephritis and IgG4 myeloperoxidase-anti-neutrophil cytoplasmic antibody positive crescentic glomerulonephritis: A case report.

    Science.gov (United States)

    Su, Tao; Yang, Li; Cui, Zhao; Wang, Su-Xia; Zhao, Ming-Hui

    2017-05-01

    IgG4-related disease (IgG4-RD) is a newly recognized systemic disease. The typical pathological finding in the kidney is abundant IgG4-positive plasma cell infiltration with characteristic storiform fibrosis in the interstitium. Antibodies of the IgG4 subclass have been linked to certain autoimmune diseases including antiproteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) of the IgG4 subclass. Here, we report a rare case of kidney injury with concurrent typical IgG4-related tubulointerstitial nephritis and IgG4 subclass of myeloperoxidase (MPO) ANCA-positive necrotizing crescentic glomerulonephritis. A 42-year-old Chinese man presented with repeated epigastric pain, sausage-shaped pancreas observed morphologically in computed tomography, effectiveness of prednisone therapy and was diagnosed with autoimmune pancreatitis. He subsequently developed acute kidney injury. The patient had an elevated serum IgG4, eosinophilia, and positive MPO-ANCA of IgG4-dominant subclass. Renal biopsy revealed necrotizing crescentic nephritis and typical IgG4-related tubulointerstitial nephritis. The patient was treated with a combination of corticosteroids and cyclophosphamide, and a course of rituximab was later added to deplete peripheral B cells. The patient responded well and his renal function improved. This is the first case report of an IgG4-RD with concurrent IgG4-related tubulointerstitial nephritis and IgG4 MPO-ANCA-associated necrotizing crescentic glomerulonephritis. It raises the difficulty in differentiation diagnosis of the two separate diseases that is worthy of further study.

  19. Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

    Science.gov (United States)

    Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

    2011-11-01

    Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

  20. Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

    Science.gov (United States)

    Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

    2013-04-01

    Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

  1. Role of Epigenetic Histone Modifications in Diabetic Kidney Disease Involving Renal Fibrosis

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    Jing Sun

    2017-01-01

    Full Text Available One of the commonest causes of end-stage renal disease is diabetic kidney disease (DKD. Renal fibrosis, characterized by the accumulation of extracellular matrix (ECM proteins in glomerular basement membranes and the tubulointerstitium, is the final manifestation of DKD. The TGF-β pathway triggers epithelial-to-mesenchymal transition (EMT, which plays a key role in the accumulation of ECM proteins in DKD. DCCT/EDIC studies have shown that DKD often persists and progresses despite glycemic control in diabetes once DKD sets in due to prior exposure to hyperglycemia called “metabolic memory.” These imply that epigenetic factors modulate kidney gene expression. There is evidence to suggest that in diabetes and hyperglycemia, epigenetic histone modifications have a significant effect in modulating renal fibrotic and ECM gene expression induced by TGF-β1, as well as its downstream profibrotic genes. Histone modifications are also implicated in renal fibrosis through its ability to regulate the EMT process triggered by TGF-β signaling. In view of this, efforts are being made to develop HAT, HDAC, and HMT inhibitors to delay, stop, or even reverse DKD. In this review, we outline the latest advances that are being made to regulate histone modifications involved in DKD.

  2. Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers

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    Hyeon Joo Jeong

    2016-01-01

    Full Text Available Tubulointerstitial nephritis (TIN is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjögren syndrome, or anti-neutrophil cytoplasmic antibody–associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

  3. Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis.

    Science.gov (United States)

    Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Park, Daeui; Kim, Dae Hyun; Choi, Yeun Ja; Lee, Eun Kyeong; Kim, Kyung Mok; Park, June Whoun; Yu, Byung Pal; Chung, Hae Young

    2017-01-31

    Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-κBIZ (also known as IκBζ) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-κBIZ and of IL-6 and MCP-1 (both known to be regulated by NF-κBIZ) during aging. The up-regulation of NF-κBIZ in aged rat kidneys coincided with increased macrophage infiltration. In LPS-treated macrophages, oxidative stress was found to play a pivotal role in NF-κBIZ expression, suggesting age-related oxidative stress is associated with NF-κBIZ activation. Furthermore, these in vitro findings were confirmed in LPS-treated old rats, which showed higher levels of oxidative stress and NF-κBIZ in kidneys than LPS-treated young rats. Additional in vitro experiments using macrophages and kidney fibroblasts demonstrated NF-κBIZ and related cytokines participate in fibrosis. In particular, increased levels of NF-κBIZ-associated cytokines in macrophages significantly up-regulated TGF-β induced kidney fibroblast activation. Moreover, experiments with NF-κBIZ knocked down macrophages showed reduced TGF-β-induced kidney fibroblast activation. The findings of the present study provide evidence regarding an involvement of NF-κBIZ in age-associated progressive renal fibrosis and provides potential targets for its prevention.

  4. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

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    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  5. Perivascular radiofrequency renal denervation lowers blood pressure and ameliorates cardiorenal fibrosis in spontaneously hypertensive rats

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    Zhang, Yan; Su, Linan; Zhang, Yunrong; Wang, Qiang; Yang, Dachun; Li, De; Yang, Yongjian; Ma, Shuangtao

    2017-01-01

    Background Catheter-based renal denervation (RDN) is a promising approach to treat hypertension, but innervation patterns limit the response to endovascular RDN and the post-procedural renal artery narrowing or stenosis questions the endovascular ablation strategy. This study was performed to investigate the anti-hypertensive and target organ protective effects of perivascular RDN in spontaneously hypertensive rats (SHR). Methods SHR and normotensive Wistar-Kyoto (WKY) rats were divided into sham group (n = 10), radiofrequency ablation group (n = 20) in which rats received bilateral perivascular ablation with radiofrequency energy (2 watts), and chemical (10% phenol in 95% ethanol) ablation group (n = 12). The tail-cuff blood pressure was measured before the ablation and on day 14 and day 28 after the procedure. The plasma levels of creatinine, urea nitrogen, and catecholamines, urinary excretion of electrolytes and protein, and myocardial and glomerular fibrosis were analyzed and compared among the groups on day 28 after the procedure. Results We identified that 2-watt is the optimal radiofrequency power for perivascular RDN in rats. Perivascular radiofrequency and chemical ablation achieved roughly comparable blood pressure reduction in SHR but not in WKY on day 14 and day 28 following the procedure. Radiofrequency-mediated ablation substantially destroyed the renal nerves surrounding the renal arteries of both SHR and WKY without damaging the renal arteries and diminished the expression of tyrosine hydroxylase, the enzyme marker for postganglionic sympathetic nerves. Additionally, perivascular radiofrequency ablation also decreased the plasma catecholamines of SHR. Interestingly, both radiofrequency and chemical ablation decreased the myocardial and glomerular fibrosis of SHR, while neither increased the plasma creatinine and blood urea nitrogen nor affected the urinary excretion of electrolytes and protein when compared to sham group. Conclusions Radiofrequency

  6. Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

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    Fatima Khaja

    2016-01-01

    Full Text Available Since its discovery, small interfering RNA (siRNA has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA not easily accessed by conventional drugs. Hence, RNA interference (RNAi therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs. This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF, an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP, showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases.

  7. Sorafenib ameliorates renal fibrosis through inhibition of TGF-β-induced epithelial-mesenchymal transition.

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    Lining Jia

    Full Text Available This study was to investigate whether sorafenib can inhibit the progression of renal fibrosis and to study the possible mechanisms of this effect.Eight-week-old rats were subjected to unilateral ureteral obstruction (UUO and were intragastrically administered sorafenib, while control and sham groups were administered vehicle for 14 or 21 days. NRK-52E cells were treated with TGF-β1 and sorafenib for 24 or 48 hours. HE and Masson staining were used to visualize fibrosis of the renal tissue in each group. The expression of α-SMA and E-cadherin in kidney tissue and NRK-52E cells were performed using immunohistochemistry and immunofluorescence. The apoptosis rate of NRK-52E cells was determined by flow cytometry analysis. The protein levels of Smad3 and p-Smad3 in kidney tissue and NRK-52E cells were detected by western blot analysis.HE staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration in the sorafenib-treated-UUO groups were significantly decreased compared with the vehicle-treated-UUO group (p<0.05. Masson staining showed that the area of fibrosis was significantly decreased in the sorafenib-treated-UUO groups compared with vehicle-treated-UUO group (p<0.01. The size of the kidney did not significantly increase; the cortex of the kidney was thicker and had a richer blood supply in the middle-dose sorafenib group compared with the vehicle-treated-UUO group (p<0.05. Compared with the vehicle-treated-UUO and TGF-β-stimulated NRK-52E groups, the expression of a-SMA and E-cadherin decreased and increased, respectively, in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (p<0.05. The apoptotic rate of NRK-52E cells treated with sorafenib decreased for 24 hours in a dose-dependent manner (p<0.05. Compared with the vehicle-treated UUO and TGF-β-stimulated NRK-52E groups, the ratio of p-Smad3 to Smad3 decreased in the sorafenib-treated groups (p<0.05.Our results suggest that

  8. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    Science.gov (United States)

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  9. Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia-reperfusion in mice

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    Shailendra P. Singh

    2015-08-01

    Full Text Available Glycogen synthase kinase-3β (GSK3β is a serine/threonine protein kinase that plays an important role in renal tubular injury and regeneration in acute kidney injury. However, its role in the development of renal fibrosis, often a long-term consequence of acute kidney injury, is unknown. Using a mouse model of renal fibrosis induced by ischemia-reperfusion injury, we demonstrate increased GSK3β expression and activity in fibrotic kidneys, and its presence in myofibroblasts in addition to tubular epithelial cells. Pharmacological inhibition of GSK3 using TDZD-8 starting before or after ischemia-reperfusion significantly suppressed renal fibrosis by reducing the myofibroblast population, collagen-1 and fibronectin deposition, inflammatory cytokines, and macrophage infiltration. GSK3 inhibition in vivo reduced TGF-β1, SMAD3 activation and plasminogen activator inhibitor-1 levels. Consistently in vitro, TGF-β1 treatment increased GSK3β expression and GSK3 inhibition abolished TGF-β1-induced SMAD3 activation and α-smooth muscle actin (α-SMA expression in cultured renal fibroblasts. Importantly, overexpression of constitutively active GSK3β stimulated α-SMA expression even in the absence of TGF-β1 treatment. These results suggest that TGF-β regulates GSK3β, which in turn is important for TGF-β–SMAD3 signaling and fibroblast-to-myofibroblast differentiation. Overall, these studies demonstrate that GSK3 could promote renal fibrosis by activation of TGF-β signaling and the use of GSK3 inhibitors might represent a novel therapeutic approach for progressive renal fibrosis that develops as a consequence of acute kidney injury.

  10. Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

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    Guang-xing Shui

    2017-01-01

    Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

  11. Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.

    Science.gov (United States)

    Steiger, Stefanie; Kumar, Santhosh V; Honarpisheh, Mohsen; Lorenz, Georg; Günthner, Roman; Romoli, Simone; Gröbmayr, Regina; Susanti, Heni-Eka; Potempa, Jan; Koziel, Joanna; Lech, Maciej

    2017-08-15

    Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

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    Jiang Liu

    2012-01-01

    Full Text Available The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption.

  13. Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

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    Khalaf-Allah, Abd El-Rahman M; El-Gengaihi, Souad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

    2016-01-01

    The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.

  14. Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

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    Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

    2016-06-01

    Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral

  15. Automated quantification of renal interstitial fibrosis for computer-aided diagnosis: A comprehensive tissue structure segmentation method.

    Science.gov (United States)

    Tey, Wei Keat; Kuang, Ye Chow; Ooi, Melanie Po-Leen; Khoo, Joon Joon

    2018-03-01

    Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement. An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures

  16. Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome

    International Nuclear Information System (INIS)

    Taheri, Shahram; Taheri Diana

    2009-01-01

    We report a 43-year-old woman with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) presented with a 5-day complaint of chills and fever, anorexia, nausea, and vomiting. She had elevated BUN and creatinine and urinalysis revealed decreased concentration, proteinuria, hematuria, and pyuria. A kidney biopsy showed non-caseating granulomatous tubulointerstitial nephritis. She suffered from anterior uveitis one month before, which was managed with local ophthalmic steroids. She received two months of oral high dose prednisolone, which was tapered over the next two months, and two months of 2 mg/kg cyclophosphamide. Her renal function recovered during the first two months. Her kidney and ocular symptoms did not recur during one year of follow-up. We suggest short course of cyclophosphamide and prednisolone for treatment of TINU syndrome to decrease the recurrence of kidney and ocular involvement. (author)

  17. [Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatological differential diagnosis with unexplained uveitis].

    Science.gov (United States)

    Häusler, U; Guminski, B; Helmchen, U; Kisters, K; Heinz, C; Braun, J

    2013-05-01

    The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

  18. Preservation of renal function by intensive glycemic control

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    Naoya Toriu

    2018-01-01

    Full Text Available We report the case of a 67-year-old Japanese woman with type 1 diabetes mellitus. At 47 years of age, her hemoglobin A1c (HbA1c was 10.0%, and she had overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic nephropathy. Intensive glycemic control was initiated and her HbA1c improved to 6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a second renal biopsy was performed. Glomerular lesions did not show progression but tubulointerstitial fibrosis and vascular lesions showed progression compared with the first biopsy. Intensive glycemic control can prevent the progression of glomerular lesions, but might not be effective for interstitial and vascular lesions.

  19. Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome.

    Science.gov (United States)

    Yokota, Tsubasa; Omachi, Kohei; Suico, Mary Ann; Kojima, Haruka; Kamura, Misato; Teramoto, Keisuke; Kaseda, Shota; Kuwazuru, Jun; Shuto, Tsuyoshi; Kai, Hirofumi

    2017-01-01

    A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

  20. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    Science.gov (United States)

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  1. Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

    Science.gov (United States)

    Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

    2015-01-01

    Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

  2. Aging aggravates long-term renal ischemia-reperfusion injury in a rat model.

    Science.gov (United States)

    Xu, Xianlin; Fan, Min; He, Xiaozhou; Liu, Jipu; Qin, Jiandi; Ye, Jianan

    2014-03-01

    Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI. Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed. Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI. Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Precision-cut kidney slices (PCKS to study development of renal fibrosis and efficacy of drug targeting ex vivo

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    Fariba Poosti

    2015-10-01

    Full Text Available Renal fibrosis is a serious clinical problem resulting in the greatest need for renal replacement therapy. No adequate preventive or curative therapy is available that could be clinically used to target renal fibrosis specifically. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, we here evaluated a precision-cut kidney slice (PCKS model as a new, multicellular ex vivo model to study the development of fibrosis and its prevention using anti-fibrotic compounds. Precision-cut slices (200-300 μm thickness were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGFβ1 (5 ng/ml for 48 h in the presence or absence of the anti-fibrotic cytokine IFNγ (1 µg/ml or an IFNγ conjugate targeted to PDGFRβ (PPB-PEG-IFNγ. Following culture, tissue viability (ATP-content and expression of α-SMA, fibronectin, collagen I and collagen III were determined using real-time PCR and immunohistochemistry. Slices remained viable up to 72 h of incubation, and no significant effects of TGFβ1 and IFNγ on viability were observed. TGFβ1 markedly increased α-SMA, fibronectin and collagen I mRNA and protein expression levels. IFNγ and PPB-PEG-IFNγ significantly reduced TGFβ1-induced fibronectin, collagen I and collagen III mRNA expression, which was confirmed by immunohistochemistry. The PKCS model is a novel tool to test the pathophysiology of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. A major advantage of the slice model is that it can be used not only for animal but also for (fibrotic human kidney tissue.

  4. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    International Nuclear Information System (INIS)

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

  5. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  6. Endostatin and kidney fibrosis in aging: a case for antagonistic pleiotropy?

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Ziman, Bruce; Marshall, Shannon; Maizel, Julien; Goligorsky, Michael S

    2014-06-15

    A recurring theme of a host of gerontologic studies conducted in either experimental animals or in humans is related to documenting the functional decline with age. We hypothesize that elevated circulating levels of a powerful antiangiogenic peptide, endostatin, represent one of the potent systemic causes for multiorgan microvascular rarefaction and functional decline due to fibrosis. It is possible that during the life span of an organism there is an accumulation of dormant transformed cells producing antiangiogenic substances (endostatin) that maintain the dormancy of such scattered malignant cells. The proof of this postulate cannot be obtained by physically documenting these scattered cells, and it rests exclusively on the detection of sequelae of shifted pro- and antiangiogenic balance toward the latter. Here we compared circulating levels of endostatin in young and aging mice of two different strains and showed that endostatin levels are elevated in the latter. Renal expression of endostatin increased ~5.6-fold in aging animals. This was associated with microvascular rarefaction and progressive tubulointerstitial fibrosis. In parallel, the levels of sirtuins 1 and 3 were significantly suppressed in aging mice in conjunction with the expression of markers of senescence. Treating young mice with endostatin for 28 days showed delayed recovery of circulation after femoral artery ligation and reduced patency of renal microvasculature but no fibrosis. In conclusion, the findings are consistent with the hypothesis on elevation of endostatin levels and parallel microvascular rarefaction and induction of renal fibrosis in aging mice. Copyright © 2014 the American Physiological Society.

  7. Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities

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    M. P. M. Graham-Brown

    2017-01-01

    Full Text Available Cardiovascular disease in patients with end-stage renal disease (ESRD is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

  8. Inhibition mechanism of compound ethanol extracts from wuweizi (fructus schisandrae chinensis) on renal interstitial fibrosis in diabetic nephropathy model mice.

    Science.gov (United States)

    Zhang, Yanqiu; Zhang, Daning; Zhang, Mianzhi

    2012-12-01

    To evaluate inhibition effect and mechanism of compound ethanol extracts from Wuweizi (Fructus Schisandrae Chinensis), Chuanxiong (Rhizoma Chuanxiong) and Muli (Cocha Ostreae) (FRC) on glomerular and tubular interstitial fibrosis in streptozocin (STZ)-induced diabetic nephropathy (ND) model mice. Twenty-seven male C57BL/6 mice were divided randomly into 3 groups: nondibetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic that were treated with 5 g x kg(-1) x day(-1) of FRC by oral gavage (D(FRC)), with 9 in each group. The protein expressions of E-cadherin, alpha-smooth muscle actin (alpha-SMA), Plasminogen Activator Inhibitor-1 (PAL-1) in renal tissues were investigated by Western blotting. The expressions of fibronectin (FN) and alpha-SMA were detected by immunohistochemical method. The morphological changes of renal tissues were observed under a microscope. Renal tissues in the D(FRC) group showed a lessened degree of fibrosis. Meanwhile, the expressions of FN, alpha-SMA and PAI-1 were significantly lower in the D(FRC) group than those in the D group (all P < 0.05). FRC can ameliorate the DN in the C57BL/6 mice, and its mechanism may relate to inhibition on the epithelial to mesenchymal transdifferentiation, endothelial-myofibroblast transition and PAL-1 expression.

  9. Excess 25-hydroxyvitamin D3 exacerbates tubulointerstitial injury in mice by modulating macrophage phenotype.

    Science.gov (United States)

    Kusunoki, Yasuo; Matsui, Isao; Hamano, Takayuki; Shimomura, Akihiro; Mori, Daisuke; Yonemoto, Sayoko; Takabatake, Yoshitsugu; Tsubakihara, Yoshiharu; St-Arnaud, René; Isaka, Yoshitaka; Rakugi, Hiromi

    2015-11-01

    Vitamin D hydroxylated at carbon 25 (25(OH)D) is generally recognized as a precursor of active vitamin D. Despite its low affinity for the vitamin D receptor (VDR), both deficient and excessive 25(OH)D levels are associated with poor clinical outcomes. Here we studied direct effects of 25(OH)D3 on the kidney using 25(OH)D-1α-hydroxylase (CYP27B1) knockout mice. The effects of 25(OH)D3 on unilateral ureteral obstruction were analyzed as proximal tubular cells and macrophages are two major cell types that take up 25(OH)D and contribute to the pathogenesis of kidney injury. Excess 25(OH)D3 in obstructed mice worsened oxidative stress and tubulointerstitial fibrosis, whereas moderate levels of 25(OH)D3 had no effects. The exacerbating effects of excess 25(OH)D3 were abolished in CYP27B1/VDR double-knockout mice and in macrophage-depleted CYP27B1 knockout mice. Excess 25(OH)D3 upregulated both M1 marker (TNF-α) and M2 marker (TGF-β1) levels of kidney-infiltrating macrophages. In vitro analyses verified that excess 25(OH)D3 directly upregulated TNF-α and TGF-β1 in cultured macrophages but not in tubular cells. TNF-α and 25(OH)D3 cooperatively induced oxidative stress by upregulating iNOS in tubular cells. Aggravated tubulointerstitial fibrosis in mice with excess 25(OH)D3 indicated that macrophage-derived TGF-β1 also had a key role in the pathogenesis of surplus 25(OH)D3. Thus, excess 25(OH)D3 worsens tubulointerstitial injury by modulating macrophage phenotype.

  10. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  11. Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find.

    Science.gov (United States)

    Raffler, Gabriele; Zitt, Emanuel; Sprenger-Mähr, Hannelore; Nagel, Mato; Lhotta, Karl

    2016-04-01

    Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed. Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied. In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels. In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease.

  12. Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

    Science.gov (United States)

    Ebihara, Itaru; Hirayama, Kouichi; Usui, Joichi; Seki, Masanori; Higuchi, Fujiko; Oteki, Takaaki; Kobayashi, Masaki; Yamagata, Kunihiro

    2006-09-01

    We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

  13. The effects of dietary fish oil on inflammation, fibrosis and oxidative stress associated with obstructive renal injury in rats.

    Science.gov (United States)

    Peake, Jonathan M; Gobe, Glenda C; Fassett, Robert G; Coombes, Jeff S

    2011-03-01

    We examined whether dietary supplementation with fish oil modulates inflammation, fibrosis and oxidative stress following obstructive renal injury. Three groups of Sprague-Dawley rats (n=16 per group) were fed for 4 wk on normal rat chow (oleic acid), chow containing fish oil (33 g eicosapentaenoic acid and 26 g docosahexaenoic acid per kg diet), or chow containing safflower oil (60 g linoleic acid per kg diet). All diets contained 7% fat. After 4 wk, the rats were further subdivided into four smaller groups (n=4 per group). Unilateral ureteral obstruction was induced in three groups (for 4, 7 and 14 days). The fourth group for each diet did not undergo surgery, and was sacrificed as controls at 14 days. When rats were sacrificed, plasma and portions of the kidneys were removed and frozen; other portions of kidney tissue were fixed and prepared for histology. Compared with normal chow and safflower oil, fish oil attenuated collagen deposition, macrophage infiltration, TGF-β expression, apoptosis, and tissue levels of arachidonic acid, MIP-1α, IL-1β, MCP-1 and leukotriene B(4). Compared with normal chow, fish oil increased the expression of HO-1 protein in kidney tissue. Fish oil intake reduced inflammation, fibrosis and oxidative stress following obstructive renal injury. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Correlation of serum and urinary matrix metalloproteases/tissue inhibitors of metalloproteases with subclinical allograft fibrosis in renal transplantation.

    Science.gov (United States)

    Hirt-Minkowski, Patricia; Marti, Hans-Peter; Hönger, Gideon; Grandgirard, Denis; Leib, Stephen L; Amico, Patrizia; Schaub, Stefan

    2014-01-01

    Progressive interstitial fibrosis and tubular atrophy (IF/TA) is a leading cause of chronic allograft dysfunction. Increased extracellular matrix remodeling regulated by matrix metalloproteases (MMPs) and their inhibitors (TIMPs) has been implicated in the development of IF/TA. The aim of this study was to investigate whether urinary/serum MMPs/TIMPs correlate with subclinical IF/TA detected in surveillance biopsies within the first 6months post-transplant. We measured eight different MMPs/TIMPs simultaneously in urine and serum samples from patients classified as normal histology (n=15), IF/TA 1 (n=15) and IF/TA 2-3 (n=10). There was no difference in urinary MMPs/TIMPs among the three groups, and only 1/8 serum MMPs/TIMPs (i.e. MMP-1) was significantly elevated in biopsies with IF/TA 2-3 (p=0.01). In addition, urinary/serum MMPs/TIMPs were not different between surveillance biopsies demonstrating an early development of IF/TA (i.e. delta IF/TA≥1 compared to a previous biopsy obtained three months before; n=11) and stable grade of IF/TA (i.e. delta IF/TA=0; n=20). Next, we investigated whether urinary/serum MMP/TIMP levels are elevated during acute subclinical tubulitis in surveillance biopsies obtained within the first 6months post-transplant (n=25). Compared to biopsies with normal histology, serum MMPs/TIMPs were not different; however, all urinary MMP/TIMP levels were numerically higher during subclinical tubulitis (MMP-1, MMP-7, TIMP-1 with p≤0.04). We conclude that urinary/serum MMPs/TIMPs do hardly correlate with existing or early developing IF/TA in surveillance biopsies obtained within the first 6months post-transplant. This could be explained by the dynamic process of extracellular matrix remodeling, which seems to be active during acute tubulo-interstitial injury/inflammation, but not in quiescent IF/TA. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Astragaloside IV suppresses transforming growth factor-β1 induced fibrosis of cultured mouse renal fibroblasts via inhibition of the MAPK and NF-κB signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Che, Xiajing; Wang, Qin; Xie, Yuanyuan; Xu, Weijia; Shao, Xinghua; Mou, Shan, E-mail: shan_mou@126.com; Ni, Zhaohui, E-mail: doctor_nzh@126.com

    2015-09-04

    Renal fibrosis, a progressive process characterized by the accumulation of extracellular matrix (ECM) leading to organ dysfunction, is a characteristic of chronic kidney diseases. Among fibrogenic factors known to regulate the renal fibrotic process, transforming growth factor-β (TGF-β) plays a central role. In the present study, we examined the effect of Astragaloside IV (AS-IV), a component of the traditional Chinese medicinal plant Astragalus membranaceus, on the processes associated with renal fibrosis in cultured mouse renal fibroblasts treated with TGF-β1. RT-PCR, western blotting, immunofluorescence staining and collagen assays showed that AS-IV suppressed TGF-β1 induced fibroblast proliferation, transdifferentiation, and ECM production in a dose-dependent manner. Examination of the underlying mechanisms showed that the effect of AS-IV on the inhibition of fibroblast differentiation and ECM formation were mediated by its modulation of the activity of the MAPK and NF-κB signaling pathways. Taken together, our results indicate that AS-IV alleviates renal interstitial fibrosis via a mechanism involving the MAPK and NF-κB signaling pathways and demonstrate the therapeutic potential of AS-IV for the treatment of chronic kidney diseases. - Highlights: • AS-IV suppressed TGF-β1 induced renal fibroblast proliferation. • AS-IV suppressed TGF-β1 induced renal fibroblast transdifferentiation. • AS-IV suppressed TGF-β1 induced ECM production. • AS-IV alleviates renal fibrosis via the MAPK and NF-κB signaling pathways.

  16. GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Tubular epithelial-mesenchymal transition (EMT has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF. The production of reactive oxygen species (ROS plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3 in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO. Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

  17. High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadolinium-containing magnetic resonance contrast agent

    DEFF Research Database (Denmark)

    Rydahl, Casper; Thomsen, Henrik S; Marckmann, Peter

    2008-01-01

    OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a serious disease affecting renal failure patients. It may be caused by some gadolinium (Gd)-containing contrast agents, including gadodiamide. The study aimed at estimating the prevalence of NSF after gadodiamide exposure for patients with chronic...

  18. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling

    NARCIS (Netherlands)

    Kern, Georg; Mair, Sabine M; Noppert, Susie-Jane; Jennings, Paul; Schramek, Herbert; Rudnicki, Michael; Mueller, Gerhard A; Mayer, Gert; Koppelstaetter, Christian

    2014-01-01

    Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the

  19. Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

    Directory of Open Access Journals (Sweden)

    W. Lu

    Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

  20. Monomeric neutrophil gelatinase associated lipocalin is associated with tubulointerstitial damage in chronic kidney disease

    Science.gov (United States)

    Nickolas, Thomas L.; Forster, Catherine; Sise, Meghan E.; Barasch, Nicholas; Valle, David Solá-Del; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-01-01

    The rate of progression of chronic kidney disease (CKD) is difficult to predict using single measurements of serum creatinine or proteinuria. On the other hand, documented tubulointerstitial disease presages worsening CKD, but kidney biopsy is not practical for routine use and generally does not sample the tubulointerstitial compartment of the medulla. Perhaps a urine test that correlates with specific histological findings may serve as a surrogate for the kidney biopsy. Here we compared both immunoblot analysis (under non-reducing conditions) and a commercially available monomer immunoassays of Neutrophil Gelatinase Associated Lipocalin (NGAL) with pathological changes found in kidney biopsies, to determine whether specific histological characteristics associated with a specific NGAL species. We found that the urine of patients with advanced CKD contained NGAL monomers as well as higher molecular weight complexes containing NGAL, identified by MALDI-TOF/TOF mass spectroscopy. The NGAL monomer significantly correlated with glomerular filtration rate, interstitial fibrosis and tubular atrophy. Hence, specific assays of the NGAL monomer implicate histology associated with progressive, severe CKD. PMID:22695331

  1. Cell-type-specific activation of mitogen-activated protein kinases in PAN-induced progressive renal disease in rats

    International Nuclear Information System (INIS)

    Park, Sang-Joon; Jeong, Kyu-Shik

    2004-01-01

    We examined the time-course activation and the cell-type specific role of MAP kinases in puromycin aminonucleoside (PAN)-induced renal disease. The maximal activation of c-Jun-NH 2 -terminal kinase (JNK), extracellular signal regulated kinase (ERK), and p38 MAP kinase was detected on Days 52, 38, and 38 after PAN-treatment, respectively. p-JNK was localized in mesangial and proximal tubular cells at the early renal injury. It was expressed, therefore, in the inflammatory cells of tubulointerstitial lesions. While, p-ERK was markedly increased in the glomerular regions and macrophages p-p38 was observed in glomerular endothelial cells, tubular cells, and some inflammatory cells. The results show that the activation of MAP kinases in the early renal injury by PAN-treatment involves cellular changes such as cell proliferation or apoptosis in renal native cells. The activation of MAP kinases in infiltrated inflammatory cells and fibrotic cells plays an important role in destructive events such as glomerulosclerosis and tubulointerstitial fibrosis

  2. Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

    Science.gov (United States)

    Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

    2014-05-01

    The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

  3. Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens.

    Science.gov (United States)

    Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Harada, Kenichi; Takata, Takuma; Saeki, Takako; Ubara, Yoshifumi; Sato, Yasuharu; Nagata, Michio

    2016-09-01

    IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin-positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD. Copyright © 2016 The Authors. Published

  4. Renal denervation prevents long-term sequelae of ischemic renal injury

    Science.gov (United States)

    Kim, Jinu; Padanilam, Babu J.

    2014-01-01

    Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

  5. Urinary collagen degradation products as early markers of progressive renal fibrosis

    DEFF Research Database (Denmark)

    Hijmans, Ryanne S.; Rasmussen, Daniel Guldager Kring; Yazdani, Saleh

    2017-01-01

    -fibrotic S1P-receptor modulator FTY720 treatment. Methods: Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12). Six weeks post-injection, all underwent renal biopsy, and FTY720-treatment started in ADR-rats (n = 8) and controls (n = 6...... controls, P ADR-rats versus controls...

  6. An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

    Science.gov (United States)

    Zhang, Zhi-Hao; Vaziri, Nosratola D.; Wei, Feng; Cheng, Xian-Long; Bai, Xu; Zhao, Ying-Yong

    2016-01-01

    Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID:26903149

  7. Fimasartan, a Novel Angiotensin-Receptor Blocker, Protects against Renal Inflammation and Fibrosis in Mice with Unilateral Ureteral Obstruction: the Possible Role of Nrf2

    Science.gov (United States)

    Kim, Soojeong; Kim, Sung Jun; Yoon, Hye Eun; Chung, Sungjin; Choi, Bum Soon; Park, Cheol Whee; Shin, Seok Joon

    2015-01-01

    Objectives: A newly developed angiotensin II receptor blocker, fimasartan, is effective in lowering blood pressure through its action on the renin-angiotensin system. Renal interstitial fibrosis, believed to be due to oxidative injury, is an end-stage process in the progression of chronic kidney disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to regulate cellular oxidative stress and induce expression of antioxidant genes. In this study we investigated the role of Nrf2 in fimasartan-mediated antioxidant effects in mice with renal fibrosis induced by unilateral ureteral obstruction (UUO). Materials and Methods: UUO was induced surgically in mice, followed by either no treatment with fimasartan or the intraperitoneal administration of fimasartan (3 mg/kg/day). On day 7, we evaluated the changes in the renin-angiotensin system (RAS) and the expression of Nrf2 and its downstream antioxidant genes, as well as renal inflammation, apoptosis, and fibrosis in the obstructed kidneys. The effect of fimasartan on the Nrf2 pathway was also investigated in HK-2 cells stimulated by tumor necrosis factor-α. Results: The mice with surgically induced UUO showed increased renal inflammation and fibrosis as evidenced by histopathologic findings and total collagen content in the kidney. These effects were attenuated in the obstructed kidneys of the fimasartan-treated mice. Fimasartan treatment inhibited RAS activation and the expression of Nox1, Nox2, and Nox4. In contrast, fimasartan upregulated the renal expression of Nrf2 and its downstream signaling molecules (such as NQO1; HO-1; GSTa2 and GSTm3). Furthermore, it increased the expression of antioxidant enzymes, including CuSOD, MnSOD, and catalase. The fimasartan-treated mice had significantly less apoptosis on TUNEL staining, with decreased levels of pro-apoptotic protein and increased levels of anti-apoptotic protein. In the HK-2 cells, fimasartan treatment inhibited RAS activation, decreased expression of

  8. Renal Tubule Repair: Is Wnt/β-Catenin a Friend or Foe?

    Science.gov (United States)

    Gewin, Leslie S

    2018-01-24

    Wnt/β-catenin signaling is extremely important for proper kidney development. This pathway is also upregulated in injured renal tubular epithelia, both in acute kidney injury and chronic kidney disease. The renal tubular epithelium is an important target of kidney injury, and its response (repair versus persistent injury) is critical for determining whether tubulointerstitial fibrosis, the hallmark of chronic kidney disease, develops. This review discusses how Wnt/β-catenin signaling in the injured tubular epithelia promotes either repair or fibrosis after kidney injury. There is data suggesting that epithelial Wnt/β-catenin signaling is beneficial in acute kidney injury and important in tubular progenitors responsible for epithelial repair. The role of Wnt/β-catenin signaling in chronically injured epithelia is less clear. There is convincing data that Wnt/β-catenin signaling in interstitial fibroblasts and pericytes contributes to the extracellular matrix accumulation that defines fibrosis. However, some recent studies question whether Wnt/β-catenin signaling in chronically injured epithelia actually promotes fibrosis or repair.

  9. An unusual renal manifestation of chronic HBV infection.

    Science.gov (United States)

    Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

    2010-08-01

    Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

  10. An aqueous extract of Portulaca oleracea ameliorates diabetic nephropathy through suppression of renal fibrosis and inflammation in diabetic db/db mice.

    Science.gov (United States)

    Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-01-01

    Diabetic nephropathy is one of the most common microvascular complications of diabetes and the leading cause of end-stage renal disease. In the present study, we investigated the renoprotective effect of the aqueous extract of Portulaca oleracea (AP) on diabetic nephropathy accelerated by renal fibrosis and inflammation in type 2 diabetic db/db mice. The mice were treated with AP (300 mg/kg/day, p.o.) for ten weeks to examine the long-term effects on diabetic nephropathy and renal dysfunction. We found that AP treatment markedly lowered blood glucose to 412 ± 11.4 mg/dl and plasma creatinine level to 2.3 ± 0.8 mg/dl compared to db/db mice (p < 0.05, p < 0.01, respectively). This study also showed that treatment with AP significantly decreased water intake and urine volume in diabetic db/db mice (p < 0.05). In immunohistological study, the renal expression of transforming growth factor-β1 (TGF-β1), advanced glycation end products (AGE), and intercellular adhesion molecule (ICAM)-1 markedly increased in the renal cortex of untreated db/db mice (p < 0.01). In contrast, AP treatment significantly reduced these expressions to 50 ± 2.1%, 48 ± 2.8%, 61 ± 1.1%, respectively (p < 0.01). Furthermore, NF-κB p65 activation in renal tissues markedly increased in untreated db/db mice, which was significantly suppressed by AP treatment. Taken together, these findings suggest that AP attenuates diabetic nephropathy through inhibition of renal fibrosis and inflammation in db/db mice.

  11. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest.

    Science.gov (United States)

    Chen, Wenxia; Yan, Yongbin; Song, Chundong; Ding, Ying; Du, Tao

    2017-12-14

    Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. Hepatocyte growth factor in renal failure: promise and reality.

    Science.gov (United States)

    Vargas, G A; Hoeflich, A; Jehle, P M

    2000-04-01

    Can science discover some secrets of Greek mythology? In the case of Prometheus, we can now suppose that his amazing hepatic regeneration was caused by a peptide growth factor called hepatocyte growth factor (HGF). Increasing evidence indicates that HGF acts as a multifunctional cytokine on different cell types. This review addresses the molecular mechanisms that are responsible for the pleiotropic effects of HGF. HGF binds with high affinity to its specific tyrosine kinase receptor c-met, thereby stimulating not only cell proliferation and differentiation, but also cell migration and tumorigenesis. The three fundamental principles of medicine-prevention, diagnosis, and therapy-may be benefited by the rational use of HGF. In renal tubular cells, HGF induces mitogenic and morphogenetic responses. In animal models of toxic or ischemic acute renal failure, HGF acts in a renotropic and nephroprotective manner. HGF expression is rapidly up-regulated in the remnant kidney of nephrectomized rats, inducing compensatory growth. In a mouse model of chronic renal disease, HGF inhibits the progression of tubulointerstitial fibrosis and kidney dysfunction. Increased HGF mRNA transcripts were detected in mesenchymal and tubular epithelial cells of rejecting kidney. In transplanted patients, elevated HGF levels may indicate renal rejection. When HGF is considered as a therapeutic agent in human medicine, for example, to stimulate kidney regeneration after acute injury, strategies need to be developed to stimulate cell regeneration and differentiation without an induction of tumorigenesis.

  13. Role of TREM1-DAP12 in renal inflammation during obstructive nephropathy.

    Directory of Open Access Journals (Sweden)

    Alessandra Tammaro

    Full Text Available Tubulo-interstitial damage is a common finding in the chronically diseased kidney and is characterized by ongoing inflammation and fibrosis leading to renal dysfunction and end-stage renal disease. Upon kidney injury, endogenous ligands can be released which are recognized by innate immune sensors to alarm innate immune system. A new family of innate sensors is the family of TREM (triggering receptor expressed on myeloid cell. TREM1 is an activating receptor and requires association with transmembrane adapter molecule DAP12 (DNAX-associated protein 12 for cell signaling. TREM1-DAP12 pathway has a cross-talk with intracellular signaling pathways of several Toll-like receptors (TLRs and is able to amplify TLR signaling and thereby contributes to the magnitude of inflammation. So far, several studies have shown that TLRs play a role in obstructive nephropathy but the contribution of TREM1-DAP12 herein is unknown. Therefore, we studied TREM1 expression in human and murine progressive renal diseases and further investigated the role for TREM1-DAP12 by subjecting wild-type (WT, TREM1/3 double KO and DAP12 KO mice to murine unilateral ureter obstruction (UUO model. In patients with hydronephrosis, TREM1 positive cells were observed in renal tissue. We showed that in kidneys from WT mice, DAP12 mRNA and TREM1 mRNA and protein levels were elevated upon UUO. Compared to WT mice, DAP12 KO mice displayed less renal MCP-1, KC and TGF-β1 levels and less influx of macrophages during progression of UUO, whereas TREM1/3 double KO mice displayed less renal MCP-1 level. Renal fibrosis was comparable in WT, TREM1/3 double KO and DAP12 KO mice. We conclude that DAP12, partly through TREM1/3, is involved in renal inflammation during progression of UUO.

  14. Breast Regression Protein-39/Chitinase 3-Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts.

    Science.gov (United States)

    Montgomery, Tinika A; Xu, Leyuan; Mason, Sherene; Chinnadurai, Amirtha; Lee, Chun Geun; Elias, Jack A; Cantley, Lloyd G

    2017-11-01

    The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α 2 (IL13R α 2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI. In wild-type mice, failure to resolve tubular injury after unilateral ischemia-reperfusion injury (U-IRI) led to sustained low-level Chi3l1 mRNA expression by renal cells and promoted macrophage persistence and severe interstitial fibrosis. Analysis of macrophages isolated from wild-type kidneys 14 days after U-IRI revealed high-level expression of the profibrotic BRP-39 receptor Ptgdr2 / Crth2 and expression of the profibrotic markers Lgals3 , Pdgfb , Egf , and Tgfb In comparison, injured kidneys from mice lacking BRP-39 had significantly fewer macrophages, reduced expression of profibrotic growth factors, and decreased accumulation of extracellular matrix. BRP-39 depletion did not affect myofibroblast accumulation but did attenuate myofibroblast expression of Col1a1 , Col3a1 , and Fn1 Together, these results identify BRP-39 as an important activator of macrophage-myofibroblast crosstalk and profibrotic signaling in the setting of maladaptive kidney repair. Copyright © 2017 by the American Society of Nephrology.

  15. Nephrogenic systemic fibrosis versus contrast-induced nephropathy: risks and benefits of contrast-enhanced MR and CT in renally impaired patients

    DEFF Research Database (Denmark)

    Martin, Diego R; Semelka, Richard C; Chapman, Arlene

    2009-01-01

    -sectional imaging modality. Factors to consider include the relative risks of the contrast agent. Other factors include the relative procedural risks, including radiation risks and the relative expected diagnostic yield of the examination technique (12). In this review we describe both nephrogenic systemic fibrosis...... and contrast-induced nephropathy to compare the implications with regard to relative risks and benefits of contrast-enhanced MRI or CT in patients with impaired renal function. J. Magn. Reson. Imaging 2009;30:1350-1356. (c) 2009 Wiley-Liss, Inc....

  16. Assessment of Liver Fibrosis by Transient Elastography Should Be Done After Hemodialysis in End Stage Renal Disease Patients with Liver Disease.

    Science.gov (United States)

    Taneja, Sunil; Borkakoty, Amritangsu; Rathi, Sahaj; Kumar, Vivek; Duseja, Ajay; Dhiman, Radha K; Gupta, Krishan L; Chawla, Yogesh

    2017-11-01

    The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD). Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE. Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8-23.1] vs. 11.2 [95% CI 8.8-13.7] kPa, p  or  2.5 L (8.6 [95% CI 5.7-11.5] vs. 5.1 [95% CI 2.9-7.5], p = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46-0.97], versus 0.64 [95% CI 0.38-0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively. LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis.

  17. Role for transforming growth factor-beta1 in alport renal disease progression.

    Science.gov (United States)

    Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

    1999-11-01

    Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

  18. Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

    Science.gov (United States)

    Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

    2015-10-01

    The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

  19. Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

    Science.gov (United States)

    Wang, Jing; Wen, Yubing; Zhou, Mengyu; Shi, Xiaoxiao; Jiang, Lanping; Li, Mingxi; Yu, Yang; Li, Xuemei; Li, Xuewang; Zhang, Wen; Lundquist, Andrew L; Chen, Limeng

    2017-06-02

    This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21 + follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.

  20. Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice.

    Science.gov (United States)

    Inui, Yosuke; Mochida, Hideki; Yamairi, Fumiko; Okada, Miyoko; Ishida, Junji; Fukamizu, Akiyoshi; Arakawa, Kenji

    2013-05-01

    Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyper-filtration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb/Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction.

  1. Changing spectrum of renal disease in HIV

    Directory of Open Access Journals (Sweden)

    R. Sunil

    2016-12-01

    Full Text Available The study was done to evaluate the spectrum of various renal histopathological lesions in patients infected with HIV (Human Immunodeficiency Virus.32 HIV positive patients underwent Renal biopsy over a period of 3 years from October 2013 to September 2016 who had presented with renal dysfunction and urine sediment abnormalities. Out of 32 patients, 24 were males and 8 were females. The mode of transmission of disease was sexual in 25 patients.14 patients presented with Nephrotic range proteinuria and 11 patients underwent RRT (renal replacement therapy. Majority of patients had tubulointerstitial lesions (18 patients followed by glomerular lesions (14 patients.24 patients were receiving HAART (Highly active antiretroviral therapy and majority of them had tubulointerstitial lesions. Hence Renal biopsy is indicated in HIV patients presenting with renal failure to arrive at proper diagnosis and treatment.

  2. The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods.

    Science.gov (United States)

    Xiang, Zheng; Sun, Hao; Cai, Xiaojun; Chen, Dahui

    2016-04-01

    Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

  3. Chronic Administration of Oil Palm (Elaeis guineensis Leaves Extract Attenuates Hyperglycaemic-Induced Oxidative Stress and Improves Renal Histopathology and Function in Experimental Diabetes

    Directory of Open Access Journals (Sweden)

    Varatharajan Rajavel

    2012-01-01

    Full Text Available Oil palm (Elaeis guineensis leaves extract (OPLE has antioxidant properties and because oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN, we tested the hypothesis that OPLE prevents diabetes renal oxidative stress, attenuating injury. Sprague-Dawley rats received OPLE (200 and 500 mg kg−1 for 4 and 12 weeks after diabetes induction (streptozotocin 60 mg kg−1. Blood glucose level, body and kidney weights, urine flow rate (UFR, glomerular filtration rate (GFR, and proteinuria were assessed. Oxidative stress variables such as 8-hydroxy-2′-deoxyguanosine (8-OHdG, glutathione (GSH, and lipid peroxides (LPO were quantified. Renal morphology was analysed, and plasma transforming growth factor-beta1 (TGF-β1 was measured. Diabetic rats demonstrated increase in blood glucose and decreased body and increased kidney weights. Renal dysfunction (proteinuria, elevations in UFR and GFR was observed in association with increases in LPO, 8-OHdG, and TGF-β1 and a decrease in GSH. Histological evaluation of diabetic kidney demonstrated glomerulosclerosis and tubulointerstitial fibrosis. OPLE attenuated renal dysfunction, improved oxidative stress markers, and reduced renal pathology in diabetic animals. These results suggest OPLE improves renal dysfunction and pathology in diabetes by reducing oxidative stress; furthermore, the protective effect of OPLE against renal damage in diabetes depends on the dose of OPLE as well as progression of DN.

  4. Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

    Science.gov (United States)

    Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

    2017-09-01

    A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Sobresaturacion urinaria del Oxalato de Calcio más alla de la Nefrolitiasis: La relación con el daño tubulointersticial Urinary calcium oxalate supersaturation beyond nephrolithiasis: Relationship with tubulointerstitial damage

    Directory of Open Access Journals (Sweden)

    J. E. Toblli

    2003-04-01

    Full Text Available Numerosos estudios han demostrado que el producto de la actividad iónica (PAI de oxalato de calcio (OxCa en la orina, como indicador de sobresaturación (SS urinaria, es mayor en pacientes formadores de cálculos que en sujetos normales. Más allá de la relación entre SS urinaria del OxCa y litogénesis, la exposición de OxCa al epitelio tubular puede ocasionar lesiones en la célula tubular y en el intersticio renal. Nuestro objetivo fue evaluar la posible relación entre SS urinaria de OxCa y el daño tubulointersticial (TI en un modelo animal de hiperoxaluria. Durante cuatro semanas, ratas Sprague-Dawley machos, divididas en dos grupos recibieron: grupo 1 Control [G1], (n= 8 agua, grupo 2 [G2], (n = 8 etilenglicol (ETG al 1% en el agua de beber. La SS urinaria de OxCa se valoró mediante el PAI del OxCa. Las lesiones TI se analizaron al finalizar el estudio por microscopía óptica e inmunohistoquímica. El G2 (ETG presentó valores mayores (pA number of studies have demonstrated that the urinary ion activity product (IAP of calcium oxalate (CaOx, as an index of urinary CaOx supersaturation (SS, is higher in renal stone formers than in normal subjects. Besides, the relation between CaOx SS and lithogenesis, crystal CaOx exposition can produce tubular cell as well as renal interstitial lesions. The aim of our study was to evaluate the possible relationship between CaOx SS and tubulointerstitial (TI damage in an animal model of hyperoxaluria. During four weeks, male Sprague-Dawley rats received: G1 (n=8 control regular water, and G2 (n= 8 1% ethylene glycol (ETG (precursor for oxalates in drinking water. In order to evaluate urinary CaOx SS, IAP assessed by Tisselius formula was performed. At the end of the study, renal lesions were evaluated by light microscopy and immunohistochemistry. Animals from G2 (ETG presented higher (p< 0.01 values of: a urinary oxalate excretion; b urinary CaOx SS; c crystalluria score; d proteinuria; and lower (p

  6. The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

    Science.gov (United States)

    Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

    2002-08-01

    Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

  7. Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

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    Schiffer Lena

    2012-10-01

    Full Text Available Abstract Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90% of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662

  8. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  9. Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

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    Park, C W; Lim, J H; Youn, D-Y; Chung, S; Lim, M-H; Kim, Y K; Chang, Y S; Lee, J-H

    2011-02-01

    Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

  10. Epithelial cells as active player in fibrosis: findings from an in vitro model.

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    Solange Moll

    Full Text Available Kidney fibrosis, a scarring of the tubulo-interstitial space, is due to activation of interstitial myofibroblasts recruited locally or systemically with consecutive extracellular matrix deposition. Newly published clinical studies correlating acute kidney injury (AKI to chronic kidney disease (CKD challenge this pathological concept putting tubular epithelial cells into the spotlight. In this work we investigated the role of epithelial cells in fibrosis using a simple controlled in vitro system. An epithelial/mesenchymal 3D cell culture model composed of human proximal renal tubular cells and fibroblasts was challenged with toxic doses of Cisplatin, thus injuring epithelial cells. RT-PCR for classical fibrotic markers was performed on fibroblasts to assess their modulation toward an activated myofibroblast phenotype in presence or absence of that stimulus. Epithelial cell lesion triggered a phenotypical modulation of fibroblasts toward activated myofibroblasts as assessed by main fibrotic marker analysis. Uninjured 3D cell culture as well as fibroblasts alone treated with toxic stimulus in the absence of epithelial cells were used as control. Our results, with the caveats due to the limited, but highly controllable and reproducible in vitro approach, suggest that epithelial cells can control and regulate fibroblast phenotype. Therefore they emerge as relevant target cells for the development of new preventive anti-fibrotic therapeutic approaches.

  11. G Protein-Coupled Receptor-G-Protein βγ-Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure.

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    Kamal, Fadia A; Travers, Joshua G; Schafer, Allison E; Ma, Qing; Devarajan, Prasad; Blaxall, Burns C

    2017-01-01

    Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein-coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G-protein βγ-subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR-Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR-Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor-Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI. Copyright © 2016 by the American Society of Nephrology.

  12. Post-radiational ureteric fibrosis with extrarenal renal failure as a rare complication after adjuvant treatment of gastric cancer - a case report

    International Nuclear Information System (INIS)

    Swieboda-Sadlej, A.; Staszewska-Skurczynska, M.; Piyush Vyas; Zurawinska, E.; Heleniak, H.; Kocik, J.; Danek, A.; Tragarz, E.

    2008-01-01

    The principles of chemoradiotherapy for treating patients with radically resected gastric cancer are not fully established. In many oncological centres patients with unfavourable prognostic factors who previously had radical gastrectomy are treated with Macdonald regimen which includes combined fluorouracil with radiotherapy. Statistics indicate that more then 30% patients treated with chemoradiotherapy suffer from serious complication. In this article we describe a case of a patient who developed ureteric fibrosis with consequent renal failure as a rare life threatening complication of Macdonald regimen. The patient received chemoradiotherapy because of unfavourable prognostic factors and good performance status however he was in advanced age and with other comorbidities. These data support the notion of the high toxicity of this regimen and suggest that selection of patients for this treatment should be done very carefully. This is discussed in the context of other available therapies in gastric cancer. (author)

  13. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

    Science.gov (United States)

    Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

    2015-01-01

    ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

  14. RENAL SAFETY OF PROTON PUMP INHIBITORS

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    A. I. Dyadyk

    2017-01-01

    Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility

  15. Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine.

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    Rodrigo, Ramón; Rivera, Gonzalo

    2002-08-01

    Over the last decade, oxidative stress has been implicated in the pathogenesis of a wide variety of seemingly unrelated renal diseases. Epidemiological studies have documented an association of moderate wine consumption with a decreased risk of cardiovascular and neurological diseases; however, similar studies in the kidney are still lacking. The kidney is an organ highly vulnerable to damage caused by reactive oxygen species (ROS), likely due to the abundance of polyunsaturated fatty acids in the composition of renal lipids. ROS are involved in the pathogenic mechanism of conditions such as glomerulosclerosis and tubulointerstitial fibrosis. The health benefits of moderate consumption of red wine can be partly attributed to its antioxidant properties. Indeed, the kidney antioxidant defense system is enhanced after chronic exposure to moderate amounts of wine, a response arising from the combined effects of ethanol and the nonalcoholic components, mainly polyphenols. Polyphenols behave as potent ROS scavengers and metal chelators; ethanol, in turn, modulates the activity of antioxidant enzymes. Therefore, a hypothesis that red wine causes a decreased vulnerability of the kidney to the oxidative challenges could be proposed. This view is partly supported by direct evidences indicating that wine and antioxidants isolated from red wine, as well as other antioxidants, significantly attenuate or prevent the oxidative damage to the kidney. The present hypothesis paper provides a collective body of evidence suggesting a protective role of moderate wine consumption against the production and progression of renal diseases, based on the existing concepts on the pathophysiology of kidney injury mediated by oxidative stress.

  16. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

    International Nuclear Information System (INIS)

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    2010-01-01

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  17. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  18. Renal Protection by Genetic Deletion of the Atypical Chemokine Receptor ACKR2 in Diabetic OVE Mice

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    Shirong Zheng

    2016-01-01

    Full Text Available In diabetic nephropathy (DN proinflammatory chemokines and leukocyte infiltration correlate with tubulointerstitial injury and declining renal function. The atypical chemokine receptor ACKR2 is a chemokine scavenger receptor which binds and sequesters many inflammatory CC chemokines but does not transduce typical G-protein mediated signaling events. ACKR2 is known to regulate diverse inflammatory diseases but its role in DN has not been tested. In this study, we utilized ACKR2−/− mice to test whether ACKR2 elimination alters progression of diabetic kidney disease. Elimination of ACKR2 greatly reduced DN in OVE26 mice, an established DN model. Albuminuria was significantly lower at 2, 4, and 6 months of age. ACKR2 deletion did not affect diabetic blood glucose levels but significantly decreased parameters of renal inflammation including leukocyte infiltration and fibrosis. Activation of pathways that increase inflammatory gene expression was attenuated. Human biopsies stained with ACKR2 antibody revealed increased staining in diabetic kidney, especially in some tubule and interstitial cells. The results demonstrate a significant interaction between diabetes and ACKR2 protein in the kidney. Unexpectedly, ACKR2 deletion reduced renal inflammation in diabetes and the ultimate response was a high degree of protection from diabetic nephropathy.

  19. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

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    Kanodia K

    2008-01-01

    Full Text Available Collapsing glomerulopathy (CG, characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.

  20. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

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    Georg Kern

    Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

  1. A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.

    Science.gov (United States)

    Yamaguchi, Shintaro; Maruyama, Tatsuya; Wakino, Shu; Tokuyama, Hirobumi; Hashiguchi, Akinori; Tada, Shinichiro; Homma, Koichiro; Monkawa, Toshiaki; Thomas, James; Miyashita, Kazutoshi; Kurihara, Isao; Yoshida, Tadashi; Konishi, Konosuke; Hayashi, Koichi; Hayashi, Matsuhiko; Itoh, Hiroshi

    2015-11-11

    Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not

  2. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Khurram, Misbah; Skov, Lone; Rossen, Kristian

    2007-01-01

    Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26...

  3. Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

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    Jia-Sheng Wu

    Full Text Available Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A, Radix et Rhizoma Rhei polysaccharides (P, and Radix Scutellaria flavones (F. Our previous studies have shown that a combination of A, P, and F (APF exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB. APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1, and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate

  4. Evaluation of the incidence of nephrogenic systemic fibrosis in patients with moderate renal insufficiency administered gadobenate dimeglumine for MRI

    International Nuclear Information System (INIS)

    Bryant, B.J.; Im, K.; Broome, D.R.

    2009-01-01

    Aim: To determine the incidence of nephrogenic systemic fibrosis (NSF) in stage 3 chronic kidney disease patients following intravenous exposure to gadobenate dimeglumine. Materials and methods: A prospective study was performed on 168 consecutive patients at a single institution with stage 3 chronic kidney disease who underwent clinically-indicated contrast-enhanced magnetic resonance imaging (MRI) examinations with gadobenate dimeglumine from January 2007 to March 2008. All patients were contacted by phone by investigators 3 months after MRI to verify the presence or absence of NSF signs or symptoms. If signs or symptoms suggestive of NSF developed, dermatologic referral was made and confirmatory skin biopsy performed if indicated. Results: One hundred and eighty contrast-enhanced MRI examinations with gadobenate dimeglumine were performed on the 168 patients. Twenty patients were lost to follow-up, but 160 incidents of contrast medium exposure were followed up for 3-months and 105 incidents were followed up for 6 months. The mean contrast medium dose per weight was 0.093 mmol/kg (range 0.042-0.153 mmol/kg). The mean estimated creatinine clearance was 50.4 ml/min/1.73 m 2 (range from 30-59 ml/min/1.73 m 2 ). Ten patients developed skin rashes during the 3-month follow-up period, but none were confirmed to represent NSF (0% prevalence rate). No other signs or symptoms of NSF were reported. Conclusion: Based on this limited study, NSF does not appear to occur in patients with stage 3 chronic kidney disease exposed to intravenous gadobenate dimeglumine for MRI at standard dosing of ∼0.1 mmol/kg.

  5. Presenting A Case with Tubulointerstitial Nephritis and Uveitis (TINU- Syndrome

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    E Fotouhi Ardakani

    2008-10-01

    Full Text Available Concurrence of interstitial nephritis and uveitis named tubulointestitioal nephritis and uveitis syndrome (TINU are unusual and uncommon presentations of interstitial nephritis. This syndrome is considered after ruling out other differential diagnoses. A-38-year old man presented with acute renal failure and uveitis. The histologic findings of renal biopsy showed acute tubulointestitioal nephritis. The patient had no clinical and paraclinical manifestations of other etiologies of interstitial nephritis and uveitis such as Wegener's granulomatosis , Sjogren's syndrome or sarcoidosis. The diagnosis of TINU-Syndrome was therefore considered. The patient was treated by oral and ophthalmic prednisolone and had a good response to treatment.

  6. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter

    2008-01-01

    PURPOSE OF REVIEW: The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. RECENT FINDINGS: Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  7. The incidence of IgG4-positive plasma cells staining TIN in patients with biopsy-proven tubulointerstitial nephritis.

    Science.gov (United States)

    Mac, Kathy; Wu, Xiao Juan; Mai, Jun; Howlin, Kenneth; Suranyi, Michael; Yong, Jim; Makris, Angela

    2017-06-01

    IgG4 disease is rare. However, IgG4 tubulointerstitial nephritis (TIN) is the most common renal manifestation. IgG4 disease is usually associated with elevated serum IgG4 levels and other organ involvement, low-density renal lesions on enhanced CT imaging and immune activation. The incidence of IgG4-TIN may be underestimated, as staining for IgG4 is not routine. This study sought to describe the prevalence of previously undiagnosed IgG4-TIN. Due to the complexity of the diagnosis, we only attempt to look at IgG4-positive plasma cell TIN as a potential indication for IgG4 renal disease. A retrospective review of native renal biopsies performed between 2002 and 2012 with a primary diagnosis of TIN was selected. Samples for which interstitial nephritis was secondary to a glomerular disease were excluded. The tissues were stained for IgG4 and scored by two blinded observers. Demographic and follow-up details were collected. This study was approved by the local ethics committee. 82 cases of interstitial nephritis from a total of 1238 renal biopsies (2002-2012) were available after staining for further assessment. 12 samples demonstrated staining consistent with the criteria for IgG4-positive plasma cell TIN, of which 3 had mildly positive staining, 7 moderately positive staining and 2 had markedly positive staining. There were no statistically significant differences in the baseline characteristics between the positive and negative staining groups. A number of cases of IgG4-positive plasma cell TIN were observed histologically that had been previously diagnosed as non-specific chronic TIN. IgG4-positive plasma cell TIN made up 1% of all renal biopsies performed over 10 years and 13% of all biopsies demonstrating TIN not related to glomerular disease. IgG4 staining should be considered routinely in biopsies demonstrating primary TIN. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Acute tubulointerstitial nephritis and uveitis syndrome: A report on four adult cases

    Directory of Open Access Journals (Sweden)

    Yosra Ben Ariba

    2017-01-01

    Full Text Available Acute tubulointerstitial nephritis and uveitis (TINU syndrome is a rare disease, generally presenting in children and young women. The interstitial nephritis may precede, follow, or develop concurrent to the uveitis. We report the clinical features and outcomes of four adult patients, aged 41-70 years with the TINU syndrome.

  9. Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis

    DEFF Research Database (Denmark)

    Landegren, Nils; Pourmousa Lindberg, Mina; Skov, Jakob

    2016-01-01

    Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patien...

  10. Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.

    Science.gov (United States)

    Mariani, Laura H; Martini, Sebastian; Barisoni, Laura; Canetta, Pietro A; Troost, Jonathan P; Hodgin, Jeffrey B; Palmer, Matthew; Rosenberg, Avi Z; Lemley, Kevin V; Chien, Hui-Ping; Zee, Jarcy; Smith, Abigail; Appel, Gerald B; Trachtman, Howard; Hewitt, Stephen M; Kretzler, Matthias; Bagnasco, Serena M

    2018-02-01

    Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37). Cortical IF, TA and II were quantified (%) on digitized whole-slide biopsy images, by five pathologists with high inter-reader agreement (intra-class correlation coefficient >0.8). Tubulointerstitial messenger RNA expression was measured in a subset of patients. Multivariable Cox proportional hazards models were fit to assess association of IF with the composite of 40% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD) and separately as well, and with complete remission (CR) of proteinuria. IF was highly correlated with TA (P  0.4, false discovery rate (FDR) < 0.01), including upstream regulators such as tumor necrosis factor, interferon gamma (IFN-gamma), and transforming growth factor beta 1 (TGF-B1), and signaling pathways for antigen presentation and hepatic fibrosis. The degree of IF is associated with risk of eGFR decline across different types of proteinuric glomerulopathy, correlates with inflammatory and fibrotic gene expression, and may have predictive value in assessing risk of progression. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  11. Sex-Differences in Renal Expression of Selected Transporters and Transcription Factors in Lean and Obese Zucker Spontaneously Hypertensive Fatty Rats

    Directory of Open Access Journals (Sweden)

    Andrea Babelova

    2015-01-01

    Full Text Available The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1 rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2, with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman’s space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1β and Hnf4α in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.

  12. Ambulatory blood pressure and tubulointerstitial injury in patients with IgA nephropathy.

    Science.gov (United States)

    Haruhara, Kotaro; Tsuboi, Nobuo; Koike, Kentaro; Kanzaki, Go; Okabayashi, Yusuke; Miyazaki, Yoichi; Kawamura, Tetsuya; Ogura, Makoto; Yokoo, Takashi

    2015-12-01

    Few studies have been conducted to assess the ambulatory blood pressure (ABP) in IgA nephropathy (IgAN) patients. This study aimed to determine the relationships between ABP and renal histopathological findings assessed using the Oxford classification (OC) and the Japanese classification (JC), which have recently established histopathological criteria for IgAN. This cross-sectional study included biopsy-diagnosed IgAN patients, in whom both a renal biopsy and ABP measurement were performed. The histopathological findings were assessed using the OC and the JC and were analyzed in relation to the ABP. A total of 111 IgAN patients were included. The score of interstitial fibrosis and tubular atrophy (T score) using the OC was a significantly associated factor with both the daytime and nighttime ABP values. In contrast, the other histopathological scores, including mesangial hypercellularity, endocapillary hypercellularity and segmental glomerulosclerosis, did not show significant associations with the ABP. The histological grade (H-grade) using the JC, which was based on the sum of injured glomeruli, was associated with the daytime ABP, but not with the nighttime ABP. The associations between the T score using the OC (%) and the daytime and nighttime ABP values were independent of age, gender, renal function, proteinuria and the use of antihypertensive medications, whereas the H-grade using the JC (%) did not show significant associations after adjusting for these clinical parameters. These results suggest that the T score using the OC is the most relevant renal histopathological parameter associated with abnormalities of circadian blood pressure in IgAN patients.

  13. Congenital ureteropelvic junction obstruction: physiopathology, decoupling of tout court pelvic dilatation-obstruction semantic connection, biomarkers to predict renal damage evolution.

    Science.gov (United States)

    Alberti, C

    2012-02-01

    The widespread use of fetal ultrasonography results in a frequent antenatally observation of hydronephrosis, ureteropelvic junction obstruction (UPJO) accounting for the greatest fraction of congenital obstructive nephropathy. UPJO may be considered, in most cases, as a functional obstructive condition, depending on defective fetal smooth muscle/nerve development at this level, with lack of peristaltic wave propagation--aperistaltic segment--and, therefore, poor urine ejection from the renal pelvis into the ureter. The UPJO-related physiopathologic events are, at first, the compliant dilatation of renal pelvis that, acting as hydraulic buffer, protects the renal parenchyma from the rising intrapelvic pressure-related potential damages, and, subsequently, beyond such phase of dynamic balance, the tubular cell stretch-stress induced by increased intratubular pressure and following parenchymal inflammatory lesions: inflammatory infiltrates, fibroblast proliferation, activation of myofibroblasts, tubulo-interstitial fibrosis. Reactive oxygen species (ROS), nitric oxide (NO), several chemo- and cytokines, growth factors, prostaglandins and eicosanoids, angiotensin-II are the main pathogenetic mediators of the obstructive nephropathy. Apoptosis of tubular cells is the major cause of the tubular atrophy, together with epithelial-mesenchymal transdifferentiation. Some criticisms on tout court semantic renal pelvis dilatation-obstruction connection have been raised considering that the renal pelvis expansion isn't, in any case, linked to an ostructive condition, as it may be verified by diuretic (furosemide) renogram together with scintiscan-based evaluation of differential renal function. In this regard, rather than repetitive invasive nuclear procedures that expose the children to ionizing radiations, an intriguing noninvasive strategy, based on the evaluation of urinary biomarkers and urinary proteome, can define the UPJO-related possible progress of parenchymal lesions

  14. Demonstration of the proliferation marker Ki-67 in renal biopsies: correlation to clinical findings.

    Science.gov (United States)

    Nabokov, A; Waldherr, R; Ritz, E

    1997-07-01

    Assessment of cell proliferation in renal biopsy samples is a potentially promising analytical tool to evaluate disease activity. So far no information is available on the correlation between proliferative activity in different anatomic compartments of the kidney and clinical symptoms. To elucidate this issue, we examined renal biopsy specimens from 20 patients with systemic vasculitis (15 Wegener's granulomatosis, five microscopic polyangiitis), 20 patients with immunoglobulin (Ig) A nephropathy (IgAN), 13 patients with minimal-change disease (MCD), 11 patients with tubulointerstitial nephritis, and five patients with diabetes mellitus. The streptavidin-biotin-peroxidase complex technique was applied to autoclave-pretreated, formalin-fixed, paraffin-embedded tissue sections to label different cell types with the antibody MIB1 directed against the Ki-67 antigen. Proliferation index (PI) was estimated as the number of positively stained nuclei per glomerular cross-section or per square millimeter section area. The interstitial cells were discriminated by additional staining of Ki-67-processed samples with specific immune markers. In patients with vasculitis, PI was considerably elevated in the extracapillary glomerular compartment (0.86), in proximal tubules (6.24), and in the interstitium (8.62). High proliferative activity was also noted in interstitium (3.98) and proximal tubules (1.35) of patients with IgAN. Of particular interest was the increased interstitial proliferative activity (15.0) in diabetic patients. Resident renal cells, but not infiltrating cells, seemed to constitute the majority of the proliferating cell population in the interstitium. In systemic vasculitis, clinical disease activity was significantly correlated to endocapillary (r(s) = 0.58), extracapillary (r(s) = 0.67), proximal tubular (r(s) = 0.67), and interstitial PI (r(s) = 0.61). By multiple linear regression analysis, proximal tubular PI was correlated to the presence of hematuria

  15. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone; Rossen, Kristian

    2006-01-01

    Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases...... of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75...... d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P

  16. Unusual Presentation Of Idiopathic Retroperitoneal Fibrosis: Case ...

    African Journals Online (AJOL)

    Idiopathic retroperitoneal fibrosis (IRF) is an uncommon entity described as progressive proliferation of connective tissues leading to a fibrous plaque-like lesions that encases the aorta and inferior vena cava inferior to the level of the renal arteries. Mass forming retroperitoneal fibrosis is rare. We present a rare case of a ...

  17. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

  18. Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

    Science.gov (United States)

    Ayasreh, Nadia; Bullich, Gemma; Miquel, Rosa; Furlano, Mónica; Ruiz, Patricia; Lorente, Laura; Valero, Oliver; García-González, Miguel Angel; Arhda, Nisrine; Garin, Intza; Martínez, Víctor; Pérez-Gómez, Vanessa; Fulladosa, Xavier; Arroyo, David; Martínez-Vea, Alberto; Espinosa, Mario; Ballarín, Jose; Ars, Elisabet; Torra, Roser

    2018-05-18

    Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Retrospective cohort study. 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Age at ESRD, rate of decline in estimated glomerular filtration rate. ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m 2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m 2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals

  19. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

    Directory of Open Access Journals (Sweden)

    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  20. Nephrogenic Systemic Fibrosis in Denmark

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne; J�rgensen, Bettina

    2013-01-01

    Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal...

  1. Nephrogenic systemic fibrosis: epidemiology update

    DEFF Research Database (Denmark)

    Marckmann, P.

    2008-01-01

    Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  2. Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma

    DEFF Research Database (Denmark)

    Hansen, P B; Dalhoff, K; Joffe, P

    1991-01-01

    The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m e...

  3. Nephrogenic systemic fibrosis

    International Nuclear Information System (INIS)

    Samtleben, W.

    2007-01-01

    A scleromyxedema-like disease was recognized in 1997. In 2000 this disorder was first published and termed nephrogenic fibrosing dermopathy because all patients had advanced renal failure. In 2006 it was discovered that the patients had a history of a preceding contrast-enhanced magnetic resonance imaging (MRI). All patients had acute or chronic severe renal insufficiency with a glomerular filtration rate (GFR) 2 . So far a total of about 215 patients with this new skin disorder have been reported to international registries. The skin thickening has a typical histology and begins in the peripheral extremities and progresses proximally, including also the abdominal wall and the head in some patients. NSF involves not only the skin, but also the muscles and other organs (e.g., lungs, heart, eyes) in some patients. Therefore the term nephrogenic systemic fibrosis (NSF) was introduced. Skin fibrosis and sclerosis are usually progressive with disabling contractures of involved joints (knees, hands, feet). NSF may be lethal in up to 28% of patients. Spontaneous remissions are rare. No generally accepted treatment is available. So far, the pathogenesis is not well understood. One hypothesis supposes a role of gadolinium liberated from the contrast agents. As patients with acute or chronic advanced renal failure (GFR 2 ) including those with hepatorenal dysfunctions are at high risk to develop NSF after exposure to gadolinium-based contrast agents, contrast-enhanced MRI should be avoided in this group and alternative diagnostic procedures should be used whenever possible. (orig.) [de

  4. Nephrogenic systemic fibrosis.

    LENUS (Irish Health Repository)

    Kennedy, C

    2010-11-05

    Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland\\'s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

  5. Nephrogenic systemic fibrosis

    Directory of Open Access Journals (Sweden)

    Bhushan Madke

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a relatively new fibrosing disorder which has caught the attention of various specialities in the past decade. NSF is an extremely disabling and often painful condition, affecting up to 13% of the individuals with chronic kidney disease. The administration of a gadolinium chelate contrast agent has been reported to induce the development of NSF, particularly in patients who have acute or chronic renal disease with a glomerular filtration rate (GFR lower than 30-mL/min/1.73 m 2 and in those with acute renal insufficiency. Mass spectroscopy studies have demonstrated particles of gadolinium in the lesional tissue. The exact pathogenesis of this curious sclerosing condition is unknown. The role of the aberrant targeting of ′circulating fibrocytes′ to the peripheral tissues and viscera has been hypothesized. NSF has distinct clinicopathological features in the setting of renal failure and needs to be looked upon as a new entity on the block. The condition is characterized by irregular indurated plaques, with amoeba-like projections and islands of sparing, chiefly on the trunk and extremities. Flexion contractures of fingers, knees, and elbow joints are known to occur in advanced cases of NSF. The course is frequently associated with painful episodes and loss of ambulation. Histopathology shows haphazard arrangement of thickened bundles of collagen, varying amount of mucin, and increased population of fibroblast-like cells in the dermis. Immunohistochemistry shows increased deposition of type-I procollagen and CD 34+ cells having fibroblastic activity. The condition is refractory to treatment with corticosteroids and immunosuppressive agents. Various modalities of therapy such as UVA1 phototherapy, imatinib mesylate, photodynamic therapy, plasmapheresis, extracorporeal photochemotherapy, and high-dose intravenous immunoglobulin have shown a moderate degree of improvement in skin thickness scores. A prudent

  6. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

  7. Nephrogenic systemic fibrosis (NSF) and gadolinium-based contrast ...

    African Journals Online (AJOL)

    Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in 2000, is a systemic disorder characterised by widespread tissue fibrosis. The first known case occurred in 1997, after the use of gadolinium-based contrast agents (GBCAs) at high doses in patients with renal failure had become routine.

  8. Non-invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological-pathological correlation analysis.

    Science.gov (United States)

    Ma, Maggie Km; Law, Helen Kw; Tse, Kin Sun; Chan, Kwok Wah; Chan, Gary Cw; Yap, Desmond Yh; Mok, Maggie My; Kwan, Lorraine Py; Tang, Sydney Cw; Choy, Bo Ying; Chan, Tak Mao

    2018-02-14

    To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. A total of 40 elastography scans were carried out (median creatinine 172.5 μmol/L [interquartile range 133.8-281.8 μmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85 (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis. © 2018 The Japanese Urological Association.

  9. Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.

    Science.gov (United States)

    Nayer, Ali; Green, Dollie F; Gonzalez-Suarez, Maria L; Sujoy, Victoria; Ikpatt, Offiong F; Thomas, David B

    2014-09-01

    Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

  10. Spectrum of pathological lesions in acute renal failure

    International Nuclear Information System (INIS)

    Kazi, J.I.; Mubarak, M.; Akhter, F.; Ahmed, E.; Naqvi, R.; Naqvi, S.A.; Rizvi, S.A.H.

    2003-01-01

    Objective: To determine the spectrum of pathological lesions in percutaneous renal biopsies of patients with acute renal failure (ARF) and to compare our findings with reported literature. Results: A total of 158 patients were studied. Of these 57 were males and 101 females. Mean age of the patients in this series were 30.7 years with a range of 6 to 75 years. Of these 61 (38.6%) had acute tubular necrosis, 36 (22.7%) acute cortical necrosis and 49(31%) patients had various types of glomerculonephriits (GN). Eight patients (5%) had acute tubulointerstitial nephritis, 3(1.8%) acute pyelonephritis and one patient had mucormycosis. Conclusion: This study showed that even in the selected population of biopsied ARF cases, there was a high prevalence of ischemic renal disease. A substantial number of cases in unexplained ARF on renal biopsy were due to various forms of glomerulonephritis. (author)

  11. Pulmonary fibrosis

    International Nuclear Information System (INIS)

    Yamakido, Michio; Okuzaki, Takeshi

    1992-01-01

    When the chest is exposed to x radiation and Co-60 gamma radiation, radiation damage may occur in the lungs 2 to 10 weeks after irradiation. This condition is generally referred to as radiation pneumonitis, with the incidence ranging from 5.4% to 91.8% in the literature. Then radiation pneumonitis may develop into pulmonary fibrosis associated with roentgenologically diffuse linear and ring-like shadows and strong contraction 6 months to one year after irradiation. Until recently, little attention has been paid to pulmonary pneumonitis as a delayed effect of A-bomb radiation. The recent study using the population of 9,253 A-bomb survivors have suggested that the prevalence of pulmonary fibrosis tended to be high in heavily exposed A-bomb survivors. Two other studies using the cohort of 16,956 and 42,728 A-bomb survivors, respectively, have shown that the prevalence of roentgenologically proven pulmonary fibrosis was higher in men than women (1.82% vs 0.41%), was increased with aging and had a higher tendency in heavily exposed A-bomb survivors. (N.K.)

  12. Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.

    Science.gov (United States)

    Zeng, Yi; Wang, Ping-Han; Zhang, Mao; Du, Jun-Rong

    2016-02-01

    The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury. Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury. Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls. The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.

  13. Familial Pulmonary Fibrosis

    Science.gov (United States)

    ... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  14. Cyclic Nucleotide Signalling in Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Elisabeth Schinner

    2015-01-01

    Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

  15. Renal disease and mitochondrial genetics.

    Science.gov (United States)

    Rötig, Agnès

    2003-01-01

    Respiratory chain (RC) deficiencies have long been regarded as neuromuscular diseases mainly originating from mutations in the mitochondrial DNA. Oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis-coupled electron transfer from substrate to oxygen through the RC, does not occur only in the neuromuscular system. Therefore, a RC deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of RC enzymes (nuclear DNA and mitochondrial DNA). Mitochondrial diseases can give rise to various syndromes or association, namely, neurologic and neuromuscular diseases, cardiac, renal, hepatic, hematological and endocrin or dermatological presentations. The most frequent renal symptom is proximal tubular dysfunction with a more or less complete de Toni-Debre-Fanconi Syndrome. A few patients have been reported with tubular acidosis, Bartter Syndrome, chronic tubulointerstitial nephritis or nephrotic syndrome. The diagnosis of a RC deficiency is difficult when only renal symptoms are present, but should be easier when another, seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria and the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance.

  16. Cyclosporine A induces senescence in renal tubular epithelial cells

    NARCIS (Netherlands)

    Jennings, Paul; Koppelstaetter, Christian; Aydin, Sonia; Abberger, Thomas; Wolf, Anna Maria; Mayer, Gert; Pfaller, Walter

    The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular

  17. Ultrasonography in chronic renal failure

    International Nuclear Information System (INIS)

    Buturovic-Ponikvar, Jadranka; Visnar-Perovic, Alenka

    2003-01-01

    Many chronic renal diseases lead to the final common state of decrease in renal size, parenchymal atrophy, sclerosis and fibrosis. The ultrasound image show a smaller kidney, thinning of the parenchyma and its hyperechogenicity (reflecting sclerosis and fibrosis). The frequency of renal cysts increases with the progression of the disease. Ultrasound generally does not allow for the exact diagnosis of an underlying chronic disease (renal biopsy is usually required), but it can help to determine an irreversible disease, assess prognosis and avoid unnecessary diagnostic or therapeutic procedures. The main exception in which the ultrasound image does not show a smaller kidney with parenchymal atrophy is diabetic nephropathy, the leading cause of chronic and end-stage renal failure in developed countries in recent years. In this case, both renal size and parenchymal thickness are preserved until end-stage renal failure. Doppler study of intrarenal vessels can provide additional information about microvascular and parenchymal lesions, which is helpful in deciding for or against therapeutic intervention and timely planning for optimal renal replacement therapy option

  18. Systemic sarcoidosis complicated of acute renal failure: about 12 cases.

    Science.gov (United States)

    Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

    2015-01-01

    The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.

  19. Renal flagellate infections in reptiles: 29 cases.

    Science.gov (United States)

    Juan-Sallés, Caries; Garner, Michael M; Nordhausen, Robert W; Valls, Xavier; Gallego, Miguel; Soto, Sara

    2014-03-01

    Renal infection with flagellated protozoa was retrospectively evaluated in 29 reptiles, including 12 turtles, 7 tortoises, and 6 chameleons; overall, 20 species of reptiles were represented. Most cases presented with nonspecific clinical signs or a combination of several concurrent diseases. Nineteen of 29 reptiles had tubulointerstitial nephritis associated with flagellates, and this lesion was considered contributory to death in 15 cases, although concurrent diseases were frequent. Infection was invasive into the renal interstitium in three reptiles due to tubular rupture and in one chameleon also spread to adjacent tissues, coelomic cavity, and blood vessels due to renal rupture. Cytologic or ultrastructural evaluation of trophozoites in two cases was consistent with diplomonad flagellates. Renal disease was often complicated with soft-tissue mineralization and/or gout. Gastrointestinal and cloacal infection with flagellates and inflammation were frequent in reptiles in which the digestive tract was available for histopathologic examination, and this supports the possibility of infections ascending the urinary tract from the cloaca. Renal disease associated with flagellate protozoa is rare in vertebrates but appears to be relevant in reptiles, particularly chelonians and chameleons.

  20. Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

    Science.gov (United States)

    Sharma, Amit; Khan, Md. Abdul Hye; Levick, Scott P.; Lee, Kin Sing Stephen; Hammock, Bruce D.; Imig, John D.

    2016-01-01

    Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT. PMID:27213332

  1. Downregulation of the S1P Transporter Spinster Homology Protein 2 (Spns2 Exerts an Anti-Fibrotic and Anti-Inflammatory Effect in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Olivier Blanchard

    2018-05-01

    Full Text Available Sphingosine kinase (SK catalyses the formation of sphingosine 1-phosphate (S1P, which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1 by the pro-inflammatory cytokines tumor necrosis factor (TNFα and interleukin (IL-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.

  2. Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia

    Czech Academy of Sciences Publication Activity Database

    Bolar, N. A.; Golzio, C.; Živná, M.; Hayot, G.; Van Hemelrijk, C.; Schepers, D.; Vandeweyer, G.; Hoischen, A.; Huyghe, J. R.; Raes, A.; Matthys, E.; Sys, E.; Azou, M.; Gubler, M. C.; Praet, M.; Van Camp, G.; McFadden, K.; Pediaditakis, I.; Přistoupilová, A.; Hodaňová, K.; Vyleťal, P.; Hartmannová, H.; Stránecký, V.; Hůlková, H.; Barešová, V.; Jedličková, I.; Sovová, J.; Hnízda, Aleš; Kidd, K.; Bleyer, A. J.; Spong, R. S.; Vande Walle, J.; Mortier, G.; Brunner, H.; Van Laer, L.; Kmoch, S.; Katsanis, N.; Loeys, B. L.

    2016-01-01

    Roč. 99, č. 1 (2016), s. 174-187 ISSN 0002-9297 R&D Projects: GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : Sec61 * tubulo-interstitial kidney disease * rare disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.025, year: 2016 http://www.sciencedirect.com/science/article/pii/S0002929716301999

  3. Relapsing tubulointerstitial nephritis in an adolescent with inflammatory bowel disease without aminosalicylate exposure.

    LENUS (Irish Health Repository)

    Shahrani Muhammad, H S

    2012-01-31

    A 14-year-old boy presented with ongoing constipation as a manifestation of newly diagnosed Crohn\\'s disease (CD) and a concomitant decline in renal function with biopsy-proven interstitial nephritis. Initiation of steroid therapy and mesalazine was associated with an improvement in symptoms and renal function. We describe a rare case of a 5-aminosalicylic acid (5-ASA)-naive patient who developed interstitial nephritis in association with CD with no evidence of other primary glomerulopathy. A unique feature of the case being a profound systemic inflammatory response at the time of diagnosis and a relapse in nephritis 2 months after cessation of mesalazine in the absence of any macroscopic colitis.

  4. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  5. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is a autosomal recessive genetic disease. Among caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  6. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... on this topic for: Parents Kids Teens Cystic Fibrosis Cystic Fibrosis and Nutrition Cystic Fibrosis (CF) Respiratory Screen: Sputum Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition View more Partner Message ...

  7. Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

    Science.gov (United States)

    Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

    2014-07-01

    The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

  8. Inhibition of WISE preserves renal allograft function.

    Science.gov (United States)

    Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

    2013-01-01

    Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

  9. Usefulness of renal scintigraphic scanning in the prognosis of acute renal failure

    International Nuclear Information System (INIS)

    Bernheim, J.; Collard, M.; Westphall, M.; Guey, A.; Traeger, J.

    1976-01-01

    The first results concerning the use of renal scintigraphic scanning using hippuran in acute renal failure (A.R.F.) are presented. The tubular stages of hippuran, extraction and secretion then excretion correspond to phenomena which are normally apparent within the first 10 minutes following the injection of hippuran, also it seemed interesting to study the changes which occur in A.R.F. 18 hospital in-patients with A.R.F. were studied, 10 of them suffering from tubulo-interstitial nephropathy (T.I.N.) 4 with acute glomerulonephritis (A.G.N.), 2 with obstruction of the urinary pathways and 2 with tubular necrosis on underlying chronic renal failure. In the 10 cases of T.I.N. the phenomenon of extraction was evident without any sign of secretion appearing during the 24 minutes of the investigation. No relationship could be found between the scintigram and the rapidity of recovery from A.R.F., but 8/10 recovered satisfactory renal function, the two others died from their disease, the A.R.F. being only secondary. It seems that the presence of an extraction phenomenon, whatever the aetiology of the A.R.F., is a parameter which authorizes the prognosis of a favorable course whereas its absence during the 24mm, of the investigation permits one to envisage an unfavorable course [fr

  10. The proximal tubular cell, a key player in renal damage

    NARCIS (Netherlands)

    Timmeren, Mirjan Miranda van

    2008-01-01

    A decline in renal function is associated with the degree of proteinuria and with histological findings of glomerulosclerosis and interstitial fibrosis. Proteinuria is not only a marker of renal damage, but ultrafiltered proteins can be toxic to the kidney, thereby contributing to

  11. Upregulation of Interleukin-33 in obstructive renal injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chang, Ya-Jen [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Su, Chia-Hao [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Tsai, Tzu-Hsien [Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chen, Shang-Der [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan (China); Yang, Jenq-Lin, E-mail: jyang@adm.cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China)

    2016-05-13

    Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.

  12. The Interplay between Inflammation and Fibrosis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Irina B. Torres

    2014-01-01

    Full Text Available Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

  13. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-09-01

    The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

  14. Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

    Science.gov (United States)

    Saad, Ahmed; Herrmann, Sandra M S; Crane, John; Glockner, James F; McKusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O; Textor, Stephen C

    2013-08-01

    Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (Pblood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly

  15. Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats.

    Science.gov (United States)

    Yin, Weiqin; Xu, Shiqing; Wang, Zai; Liu, Honglin; Peng, Liang; Fang, Qing; Deng, Tingting; Zhang, Wenjian; Lou, Jinning

    2018-01-01

    GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced. The results showed that rhGLP-1 reduced urinary albumin without influencing the body weight and food intake. rhGLP-1 could increased the serum C-peptide slightly but not lower fasting blood glucose significantly. In diabetic nephropathy rats, beside glomerular sclerosis, tubulointerstitial fibrosis was very serious. These lesions could be alleviated by rhGLP-1. rhGLP-1 decreased the expression of profibrotic factors collagen I, α-SMA, fibronectin, and inflammation factors MCP-1 and TNFα in tubular tissue and human proximal tubular cells (HK-2 cells). Furthermore, rhGLP-1 significantly inhibited the phosphorylation of NF-κB, MAPK in both diabetic tubular tissue and HK-2 cells. The inhibition of the expression of TNFα, MCP-1, collagen I and α-SMA in HK-2 cells by GLP-1 could be mimicked by blocking NF-κB or MAPK. These results indicate that rhGLP-1 exhibit renoprotective effect by alleviation of tubulointerstitial injury via inhibiting phosphorylation of MAPK and NF-κB. Therefore, rhGLP-1 may be a potential drug for treatment of diabetic nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Uses and limitations of renal scintigraphy in renal transplantation monitoring

    International Nuclear Information System (INIS)

    Heaf, J.G.; Iversen, J.

    2000-01-01

    The value of thrice weekly technetium-99m mercaptoacetyltriglycine renography after renal transplantation was investigated in 213 consecutive transplants. A grading system was used: 0 = normal renogram; 1 = normal uptake, reduced excretion; 2 = normal uptake, flat excretion curve; 3 = rising curve; 4 = reduced rate of uptake, rising curve and reduced absolute uptake; 5 = minimal uptake. The initial renogram grade (RG) was primarily a marker of ischaemic damage, being poorer with cadaver donation, long cold ischaemia (>24 h), and high donor and recipient age. High primary RG predicted primary graft non-function, long time to graft function, low discharge Cr EDTA clearance and low 1- and 5-year graft survival. Discharge RG predicted late (>6 months) graft loss. RG was highly correlated (P<0.001) with creatinine and creatinine clearance, and changes in RG were correlated with changes in renal function. A change in RG of 0.5 was non-specific, while a change of 1 or more predicted clinical complications in 95% of cases. The negative predictive value was low (58%). RG change antedated clinical diagnosis in only 38% of cases, and in only 14% of acute rejections did an RG change of 1 or more antedate a rising creatinine. RG did not contribute to the differential diagnosis between acute rejection, acute tubulointerstitial nephropathy and cyclosporine toxicity. In conclusion, an initial renography after transplantation is valuable as it measures ischaemic damage and predicts duration of graft non-function and both short and long-term graft survival. A review of the literature suggests that the indication for serial scintigraphic monitoring for functioning grafts is less certain: the diagnostic specificity is insufficient for it to be the definitive investigation for common diagnostic problems and it does not give sufficient advance warning of impending problems. (orig.)

  17. Renal Osteodystrophy

    Directory of Open Access Journals (Sweden)

    Aynur Metin Terzibaşoğlu

    2004-12-01

    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  18. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  19. Renal venogram

    Science.gov (United States)

    ... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

  20. Cystic fibrosis in adults

    Directory of Open Access Journals (Sweden)

    C. Damas

    2007-05-01

    Full Text Available The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n = 8, five female and three male, aged 20-34 years old (median = 27 years. Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients and genotyping (four patients homozygous for ΔF508 mutation.Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously.The main causes of exacerbation were respiratory infections and haemoptysis.Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis, one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia.Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy.At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics.In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults Resumo: Os autores efectuaram uma revisão de doentes adultos com fibrose quística (FQ, seguidos na consulta de Pneumologia no período de 1994-2004 (n = 8: cinco mulheres e três homens, com idades compreendidas entre 20 e 34 anos (mediana  =  27 anos, cuja idade de diagnóstico variou entre os 18 meses e os 31 anos.O diagnóstico foi obtido por prova de suor (positiva em seis doentes e estudo genético (homozigotia para a mutação ΔF508 em

  1. Imaging pulmonary fibrosis

    International Nuclear Information System (INIS)

    Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F.

    2001-01-01

    Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

  2. Angiogenesis in liver fibrosis

    NARCIS (Netherlands)

    Adlia, Amirah

    2017-01-01

    Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of

  3. Fibrosis and Cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R.; Erler, Janine T.

    2016-01-01

    The relation between fibrosis and cancer has long been debated, specifically whether desmoplasia precedes, accompanies, or succeeds tumourigenesis, progression, and metastasis. Recent reports have published opposing data, adding to the perplexity. However, what is emerging is that it is likely th...... the specific properties of the extracellular matrix (ECM) that determine the paradoxical nature of cancer-associated fibrosis....

  4. Diagnosis of cystic fibrosis

    NARCIS (Netherlands)

    H.J. Veeze

    1995-01-01

    textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

  5. Nephrogenic systemic fibrosis: A brief review

    Directory of Open Access Journals (Sweden)

    Rajesh Waikhom

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis is a fibrosing disorder of the skin that develops in patients with advanced renal failure. It mostly presents with progressive hardening or induration of the skin of the extremities. Systemic involvement is also known to occur in this entity. Exposure to gadolinium contrast for radiological evaluation has been identified as the offending agent. The condition is progressive and can be seriously disabling. Therapeutic options are limited and not rewarding in majority of the cases. Awareness of this entity is important so that proper precautionary measures can be taken at the earliest to ameliorate the condition.

  6. Renal lesions associated with autoimmune pancreatitis: CT findings

    International Nuclear Information System (INIS)

    Triantopoulou, Charikleia; Maniatis, Petros; Siafas, Ioannis; Papailiou, John; Malachias, George; Anastopoulos, John

    2010-01-01

    Background: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition characterized by IgG4-positive plasma cells. Recent evidence suggests that it is a systemic disease affecting various organs. Tubulointerstitial nephritis has been reported in association with AIP. Purpose: To investigate the incidence and types of renal involvement in patients with AIP. Material and Methods: Eighteen patients with no history of renal disease and a diagnosis of AIP (on the basis of histopathologic findings or a combination of characteristic imaging features, increased serum IgG4 levels, and response to steroid treatment) were included. All patients underwent computed tomography (CT) imaging and follow-up ranged from 6 months to 2 years. CT images were reviewed for the presence of renal lesions. Results: Seven patients had renal involvement (38.8%). None of the lesions was visible on non-contrast-enhanced CT scan. Parenchymal lesions appeared as multiple nodules showing decreased enhancement (four cases). Pyelonephritis, lymphoma, and metastases were considered in the differential diagnosis. An ill-defined low-attenuation mass-like lesion was found in one patient, while diffuse thickening of the renal pelvis wall was evident in the last two cases. Renal lesions regressed in all patients after steroid treatment, the larger one leaving a fibrous cortical scar. Conclusion: Different types of renal lesions in patients with AIP are relatively common, appearing as multiple nodules with decreased enhancement. These findings support the proposed concept of an IgG4-related systemic disease. Autoimmune disease should be suspected in cases of renal involvement in association with pancreatic focal or diffuse enlargement.

  7. Renal lesions associated with autoimmune pancreatitis: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Triantopoulou, Charikleia; Maniatis, Petros; Siafas, Ioannis; Papailiou, John (CT and Radiology Dept., ' Konstantopouleion' General Hospital, Athens (Greece)), e-mail: ctriantopoulou@gmail.com; Malachias, George; Anastopoulos, John (Radiology Dept., ' Sismanogleio' General Hospital, Athens (Greece))

    2010-07-15

    Background: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition characterized by IgG4-positive plasma cells. Recent evidence suggests that it is a systemic disease affecting various organs. Tubulointerstitial nephritis has been reported in association with AIP. Purpose: To investigate the incidence and types of renal involvement in patients with AIP. Material and Methods: Eighteen patients with no history of renal disease and a diagnosis of AIP (on the basis of histopathologic findings or a combination of characteristic imaging features, increased serum IgG4 levels, and response to steroid treatment) were included. All patients underwent computed tomography (CT) imaging and follow-up ranged from 6 months to 2 years. CT images were reviewed for the presence of renal lesions. Results: Seven patients had renal involvement (38.8%). None of the lesions was visible on non-contrast-enhanced CT scan. Parenchymal lesions appeared as multiple nodules showing decreased enhancement (four cases). Pyelonephritis, lymphoma, and metastases were considered in the differential diagnosis. An ill-defined low-attenuation mass-like lesion was found in one patient, while diffuse thickening of the renal pelvis wall was evident in the last two cases. Renal lesions regressed in all patients after steroid treatment, the larger one leaving a fibrous cortical scar. Conclusion: Different types of renal lesions in patients with AIP are relatively common, appearing as multiple nodules with decreased enhancement. These findings support the proposed concept of an IgG4-related systemic disease. Autoimmune disease should be suspected in cases of renal involvement in association with pancreatic focal or diffuse enlargement.

  8. Renal perfusion scintiscan

    Science.gov (United States)

    ... Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion Images Kidney anatomy Kidney - blood and urine flow Intravenous pyelogram References Rottenberg G, Andi AC. Renal ...

  9. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

    Directory of Open Access Journals (Sweden)

    Lena Berchtold

    Full Text Available Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50 for chronic histological changes (interstitial fibrosis and vascular lesions. PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001, while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively. On the contrary, fibroblast growth factor 23 (FGF23 and Klotho correlated only modestly with interstitial fibrosis (p = 0.045 whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively, but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61 but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038. The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61. In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

  10. Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

    Science.gov (United States)

    Mace, T F

    1976-01-01

    Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

  11. UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

    Science.gov (United States)

    2017-09-15

    Hepato/Renal Fibrocystic Disease; Autosomal Recessive Polycystic Kidney Disease; Joubert Syndrome; Bardet Biedl Syndrome; Meckel-Gruber Syndrome; Congenital Hepatic Fibrosis; Caroli Syndrome; Oro-Facial-Digital Syndrome Type I; Nephronophthisis; Glomerulocystic Kidney Disease

  12. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  13. Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent.

    Science.gov (United States)

    Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

    2017-08-15

    For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.

  14. Renal histology in the elderly: indications and outcomes.

    LENUS (Irish Health Repository)

    Brown, Catherine M

    2011-06-28

    Background: Renal disease is being increasingly diagnosed in the elderly. However, reports on biopsy-confirmed renal disease in this population are limited. The aim of this study was to give an overview of the most important indications, diagnoses and outcomes of renal biopsies in the elderly in our center. Methods: This was a retrospective review of all elderly renal biopsies over 5 years. Patients were eligible for inclusion if they were aged =65 years and had had a native kidney biopsy performed. The data recorded included age, sex, indications for biopsy, histological diagnoses and outcomes. Results: During this time, 1,372 native renal biopsies were performed. Of these, 236 (17%) were in patients aged =65 years; 150 male (64%) and 86 female (36%). The most common indications for biopsy were acute renal failure and nephrotic syndrome. Common diagnoses included pauci-immune crescentic glomerulonephritis, tubulointerstitial nephritis, membranous nephropathy, IgA nephropathy and chronic thrombotic microangiopathy. Long-term follow-up of 3 years was available for 102 patients; median serum creatinine at the time of biopsy was 427 µmol\\/L (interquartile range 204-702) and at 3 years post biopsy had fallen to 192 µmol\\/L (interquartile range 152-408). Conclusions: In our center, 17% of native kidney biopsies are performed in elderly patients aged =65 years. In our experience, this procedure was safe and had a 97% diagnostic rate. The available follow-up data of patients suggest that renal histology is not only of benefit in diagnosis but also of potential value in terms of prognosis and treatment.

  15. Renal histology in the elderly: indications and outcomes.

    LENUS (Irish Health Repository)

    2012-02-01

    Background: Renal disease is being increasingly diagnosed in the elderly. However, reports on biopsy-confirmed renal disease in this population are limited. The aim of this study was to give an overview of the most important indications, diagnoses and outcomes of renal biopsies in the elderly in our center. Methods: This was a retrospective review of all elderly renal biopsies over 5 years. Patients were eligible for inclusion if they were aged =65 years and had had a native kidney biopsy performed. The data recorded included age, sex, indications for biopsy, histological diagnoses and outcomes. Results: During this time, 1,372 native renal biopsies were performed. Of these, 236 (17%) were in patients aged =65 years; 150 male (64%) and 86 female (36%). The most common indications for biopsy were acute renal failure and nephrotic syndrome. Common diagnoses included pauci-immune crescentic glomerulonephritis, tubulointerstitial nephritis, membranous nephropathy, IgA nephropathy and chronic thrombotic microangiopathy. Long-term follow-up of 3 years was available for 102 patients; median serum creatinine at the time of biopsy was 427 micromol\\/L (interquartile range 204-702) and at 3 years post biopsy had fallen to 192 micromol\\/L (interquartile range 152-408). Conclusions: In our center, 17% of native kidney biopsies are performed in elderly patients aged =65 years. In our experience, this procedure was safe and had a 97% diagnostic rate. The available follow-up data of patients suggest that renal histology is not only of benefit in diagnosis but also of potential value in terms of prognosis and treatment.

  16. Distal renal tubular acidosis as a cause of osteomalacia in a patient with primary Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Jovelić Aleksandra

    2005-01-01

    Full Text Available Background. One half of the patients with primary Sjögren’s syndrome has extraglandular manifestations, including renal involvement. The most frequent renal lesion is tubulo-interstitial nephritis, which manifests clinically as distal tubular acidosis and may result in the development of osteomalacia. Case report. In a 29 - year-old female patient, with bilateral nephrolithiasis, the diagnosis of primary Sjögren’s syndrome, tubulo-interstitial nephritis, distal renal tubular acidosis, and hypokalemia were established. She was treated for hypokalemia. Two years later she developed bone pains and muscle weakness, she wasn’t able to walk, her proximal muscles and pelvic bones were painful, with radiological signs of pelvic bones osteopenia and pubic bones fractures. The diagnosis of osteomalacia was established and the treatment started with Schol’s solution, vitamin D and calcium. In the following two months, acidosis was corrected, and the patient started walking. Conclusion. In our patient with primary Sjögren’s syndrome and interstitial nephritis, osteomalacia was a result of the long time decompensate acidosis, so the correction of acidosis, and the supplementation of vitamin D and calcium were the integral part of the therapy.

  17. Case-control study of gadodiamide-related nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone; Rossen, Kristian

    2007-01-01

    exposed to gadodiamide develop nephrogenic systemic fibrosis. METHODS: We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were.......02). CONCLUSIONS: Increasing cumulative gadodiamide exposure, high-dose epoietin-beta treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients......BACKGROUND: Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients...

  18. A moderate response to plasmapheresis in nephrogenic systemic fibrosis

    Directory of Open Access Journals (Sweden)

    Pelin Ustuner

    2011-11-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a recently identified idiopathic cutaneous fibrosing disorder that occurs in the setting of renal failure. The disease initially called nephrogenic fibrosing dermopathy is closely linked to exposure to gadolinium-based contrast media used during magnetic resonance imaging in patients with renal insufficiency. Although little is known about the pathogenesis of this disease, the increased expression of transforming growth factor-beta has been demonstrated recently. Herein, we present a case of NSF was partially treated due to a moderate and temporary response to plasmapheresis with no recurrence for 6 months, but returned at the end of 6th month.

  19. Renal cancer.

    NARCIS (Netherlands)

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  20. Renal cancer

    NARCIS (Netherlands)

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.

    2007-01-01

    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  1. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    Science.gov (United States)

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  2. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney.

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail V W; Cooper, Arthur J L; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli J; Pihlajaniemi, Taina A; Goligorsky, Michael S

    2016-06-01

    Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to 4-fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One-month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail; Cooper, Arthur JL; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli; Pihlajaniemi, Taina; Goligorsky, Michael S

    2016-01-01

    Endostatin (EST), an anti-angiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild type mice, aging kidneys exhibited a 2–4 fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. PMID:27165830

  4. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

    Science.gov (United States)

    Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

    2012-02-01

    Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  5. Aldosterone as a renal growth factor.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-04-05

    Aldosterone regulates blood pressure through its effects on the cardiovascular system and kidney. Aldosterone can also contribute to the development of hypertension that leads to chronic pathologies such as nephropathy and renal fibrosis. Aldosterone directly modulates renal cell proliferation and differentiation as part of normal kidney development. The stimulation of rapidly activated protein kinase cascades is one facet of how aldosterone regulates renal cell growth. These cascades may also contribute to myofibroblastic transformation and cell proliferation observed in pathological conditions of the kidney. Polycystic kidney disease is a genetic disorder that is accelerated by hypertension. EGFR-dependent proliferation of the renal epithelium is a factor in cyst development and trans-activation of EGFR is a key feature in initiating aldosterone-induced signalling cascades. Delineating the components of aldosterone-induced signalling cascades may identify novel therapeutic targets for proliferative diseases of the kidney.

  6. Renal pathological implications in type 2 diabetes mellitus patients with renal involvement.

    Science.gov (United States)

    Li, Li; Zhang, Xiuhui; Li, Zhicheng; Zhang, Rui; Guo, Ruikun; Yin, Qinghua; Yang, Lichuan; Yue, Rongzheng; Su, Baihai; Huang, Songmin; Xu, Huan; He, Cijiang; Liu, Fang

    2017-01-01

    To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group

  7. A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

    Science.gov (United States)

    Mitchell, Emily P; Prozesky, Leon; Lawrence, John

    2018-01-01

    The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

  8. Syndecans in heart fibrosis.

    Science.gov (United States)

    Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir

    2016-09-01

    Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing

  9. Endomyocardial fibrosis in infancy

    Directory of Open Access Journals (Sweden)

    Jatene Marcelo Biscegli

    2003-01-01

    Full Text Available The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

  10. The effects of environmental chemicals on renal function.

    Science.gov (United States)

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-10-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

  11. Cells derived from young bone marrow alleviate renal aging.

    Science.gov (United States)

    Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

    2011-11-01

    Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

  12. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  13. Renal scan

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003790.htm Renal scan To use the sharing features on this ... anaphylaxis . Alternative Names Renogram; Kidney scan Images Kidney anatomy Kidney - blood and urine flow References Chernecky CC, ...

  14. Retroperitoneal fibrosis with pancreatic involvement – radiological appearance

    International Nuclear Information System (INIS)

    Zielonko, Joanna; Obołończyk, Łukasz

    2011-01-01

    Retroperitoneal fibrosis or Ormond’s disease is an uncommon process characterized by fibrous tissue proliferation in the retroperitoneum, usually involving the aorta, inferior vena cava and iliac vessels. Obstructive hydronephrosis is often observed due to ureteral entrapment. This report presents a case of the peripancreatic location of the disease. The role of CT and MRI in establishing diagnosis of retroperitoneal fibrosis in an atypical site is discussed. A 52-year-old woman with Hashimoto’s thyroiditis was admitted to hospital because of pain suggesting renal colic. The patient was subjected to ultrasound, CT, and MRI which did not confirm urolithiasis but revealed pancreatic infiltration. Partial pancreatectomy, left-sided adrenalectomy and splenectomy were performed. Retroperitoneal fibrosis was diagnosed in the histopathological examination. A few weeks after surgery, a complication such as pancreatitis developed. Repeat CT confirmed it and showed right hydronephrosis secondary to ureteral involvement by a mass adjacent to the common iliac artery (defined as a typical manifestation of retroperitoneal fibrosis). Nephrostomy and conservative treatment improved the clinical state of the patient. No progression of the process was observed in the follow-up examinations. Atypical retroperitoneal fibrosis remains a diagnostic challenge. Imaging techniques CT and MRI are useful tools for evaluating the extent of Ormond’s disease. An unusual distribution of the process (e.g. peripancreatic location reported in this study) requires histopathological assessment to establish the final diagnosis

  15. Renal Hemangiopericytoma

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    İbrahim Halil Bozkurt

    2015-03-01

    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  16. Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy.

    Science.gov (United States)

    Wijkström, Julia; González-Quiroz, Marvin; Hernandez, Mario; Trujillo, Zulma; Hultenby, Kjell; Ring, Anneli; Söderberg, Magnus; Aragón, Aurora; Elinder, Carl-Gustaf; Wernerson, Annika

    2017-05-01

    Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua. Follow-up urine and blood samples from both biopsy studies were collected to investigate the natural history. Case series. In the kidney biopsy study, 19 male sugarcane workers in Nicaragua with suspected MeN were investigated with questionnaires, kidney biopsies, and blood and urine analysis. Inclusion criteria were age 20 to 65 years and plasma creatinine level of 1.13 to 2.49mg/dL or estimated glomerular filtration rate (eGFR) of 30 to 80mL/min/1.73m 2 . Exclusion criteria were proteinuria with protein excretion > 3g/24 h, uncontrolled hypertension, diabetes mellitus, or other known kidney disease. In the follow up-study, blood and urine from the kidney biopsy study in Nicaragua (n=18) and our previous biopsy study of MeN cases in El Salvador (n=7) were collected 1 to 1.5 and 2 to 2.5 years after biopsy, respectively. Renal morphology, clinical, and biochemical characteristics, change in eGFR per year. eGFR was calculated using the CKD-EPI creatinine (eGFR cr ), cystatin C (eGFR cys ), and creatinine-cystatin C (eGFR cr-cys ) equations. In the kidney biopsy study, participants had a mean eGFR cr of 57 (range, 33-96) mL/min/1.73m 2 . 47% had low plasma sodium and 21% had low plasma potassium levels. 16 kidney biopsies were representative and showed glomerulosclerosis (mean, 38%), glomerular hypertrophy, and signs of chronic glomerular ischemia. Mild to moderate tubulointerstitial damage and mostly mild vascular changes were seen. In the follow up-study, median duration of follow-up was 13 (range, 13-27) months. Mean change in eGFR cr was -4.4±8.4 (range, -27.7 to 10.2) mL/min/1.73m 2 per year. Most patients had stopped working with sugarcane cultivation. 3 biopsy specimens

  17. Renal albumin absorption in physiology and pathology.

    Science.gov (United States)

    Birn, H; Christensen, E I

    2006-02-01

    Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

  18. Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

    International Nuclear Information System (INIS)

    Adachi, Takaomi; Sugiyama, Noriyuki; Gondai, Tatsuro; Yagita, Hideo; Yokoyama, Takahiko

    2013-01-01

    Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI

  19. Effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2016-10-01

    Full Text Available Objective: To study the effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure. Methods: A total of 68 patients with chronic renal failure who received hemodialysis treatment in our hospital during between October 2013 and February 2016 were selected and randomly divided into two groups, the observation group received Shenkang injection treatment in the process of dialysis, and the control group only received conventional symptomatic and supportive treatment. 8 weeks after treatment, serum was collected to determine the levels of renal function indexes, nutritional status indexes, anemia indexes and cytokines, and urine was collected to determine renal function indexes. Results: β2-MG, UA, Cr, phosphorus, IL-17, IL-23, CTGF, TGF-β1, FGF-2 and FGF-23 levels in serum as well as NGAL, KIM-1 and RBP levels in urine of observation group were significantly lower than those of control group, and TP, Alb, PA, calcium, Hb, EPO, Fe, TRF and FER levels in serum were significantly higher than those of control group. Conclusion: Shenkang injection combined with hemodialysis treatment helps to improve renal function, nutritional status and renal anemia, and reduce the synthesis of inflammation and renal interstitial fibrosis-related cytokines in patients with chronic renal failure.

  20. The Significance of Serum beta2-Microglobulin Measurement in Various Renal Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Koong, Sung Soo; Oh, Ha Yong; Han, Jin Suk; Lee, Jung Sang [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1985-03-15

    To evaluate change of serum beta{sub 2}-microglobulin concentration (sbeta{sub 2}-MG) and the usefulness of sbeta{sub 2}-MG and sbeta{sub 2}-MG/serum creatinine concentration (sCr) ratio in various renal diseases, sbeta{sub 2}-MG and sCr were measured in 25 normal controls and 90 patients of various renal diseases (16 cases of glomerulonephritis, 12 cases of acute renal failure, 8 cases of chronic renal failure, 24 cases of nephrotic syndrome, 15 cases of tubulointerstitial diseases and 15 cases of lupus nephritis) using Phadebas beta{sub 2}-Micro Test kits. The results were as follows; 1) In normal control, the mean value of sbeta{sub 2}-MG was 1.65+-0.41 mg/l and the mean value of sbeta{sub 2}-MG/sCr ratio was 0.14+-0.05. 2) In various renal diseases, the mean value of sbeta{sub 2}-MG was 6.74+-5.47 mg/l. The mean value of sbeta{sub 2}-MG/sCr ratio was 0.24+-0.11 and significantly elevated than that of normal contro1. (P<0.05). 3) The correlation between sbeta-2-MG and sCr in glomerular and tubulointerstitial disease was log sbeta{sub 2}-MG=0.90 log sCr-0.48 and its correlation coefficient was 0.78 (P<0.05). 4) In glomerular disease, the correlation between sbeta{sub 2}-MG and sCr was log sbeta{sub 2}-MG=0.89 log sCr-0.46 (r-0.76) and in tubulointerstitial disease, it was log sbeta{sub 2}-MG=0.95 1og sCr-0.59 (r-0.87). There was no significant difference between the two groups (p<0.05). 5) Among 32 cases of glomerular and tubulointerstitial disease patients, whose sCr was within normal range, 17 cases showed elevated sbeta{sub 2}-MG. The mean values of sbeta{sub 2}-MG/sCr ratio in these patients was 0.30+-0.14 and significantly elevated than that of normal control (p<0.05). 6) In 15 cases of lupus nephritis, 12 cases showed elevated sbeta{sub 2}-MG with normal sCr and 12 cases showed elevated sbeta{sub 2}-MG/sCr ratio. With above results, It was found that the sbeta{sub 2}-MG can be used as an index of glomerular filtration rate as in the case of sCr and thats

  1. Amiloidose e insuficiência renal crônica terminal associada à hanseníase Amyloidosis and end-stage renal disease associated with leprosy

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Júnior

    2010-08-01

    Full Text Available O envolvimento renal na hanseníase é diverso, incluindo glomerulonefrites, amiloidose e nefrite túbulo-intersticial. Um homem de 58 anos foi admitido com edema de membros inferiores e dispnéia. Na admissão, havia retenção de escórias nitrogenadas, anemia, hipercalemia e acidose metabólica, com necessidade de hemodiálise. Referia história de hanseníase virchoviana. Foi realizada biopsia renal, compatível com amiloidose. O paciente evoluiu estável, sem recuperação da função renal, permanecendo em tratamento hemodialítico. A hanseníase deve ser investigada em todo paciente com perda de função renal, sobretudo naqueles que apresentam lesões cutâneas ou outras manifestações sugestivas de hanseníase.Renal involvement in leprosy includes glomerulonephritis, amyloidosis and tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of lower limb edema and dyspnea. At admission, nitrogen retention, anemia, hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The patient had a history of lepromatous leprosy. A renal biopsy was performed that was compatible with amyloidosis. The patient had a stable outcome, but without renal function recovery and remained on regular hemodialysis. Leprosy should be investigated in every patient with renal function loss, particularly in those with cutaneous lesions or other manifestations suggestive of leprosy.

  2. Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

    Science.gov (United States)

    Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

    2018-06-01

    Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. An epidemic outbreak of nephrogenic systemic fibrosis in a Danish hospital

    International Nuclear Information System (INIS)

    Marckmann, Peter

    2008-01-01

    The nephrological department of Copenhagen University Hospital Herlev experienced an epidemic accumulation of patients developing nephrogenic systemic fibrosis in the period 2002-2006. Systematic studies of these patients revealed that they all had a gadodiamide-enhanced magnetic resonance examination prior to their symptoms, and that they all had severe renal insufficiency (chronic kidney disease stage 5) at the time of their exposure to gadodiamide. Besides exposure to gadodiamide, our analyses indicated that increasing cumulative gadodiamide exposure (i.e. repeated exposures), and higher serum concentrations of ionized calcium and phosphate were cofactors that raised the risk of developing nephrogenic systemic fibrosis. Higher cumulative gadodiamide exposure, higher prescribed erythropoietin dosage at exposure, and being hemodialysis patient were three factors associated with nephrogenic systemic fibrosis in its most severe form. Retrospective reviews of patients records and patient interviews revealed the large variability in symptoms and clinical course of nephrogenic systemic fibrosis, but also highlighted that the typical initial symptoms were symmetric swelling, discoloration and pain of lower legs, whereas the typical late symptoms of severely affected patients were skin thickening, stiffness, contractures, and debilitating disabilities. In conclusion, nephrogenic systemic fibrosis is a serious iatrogenic disease of patients with renal insufficiency caused by some Gd-containing contrast agents, in particular gadodiamide. Unfortunately, there is no proven curative treatment. It is therefore essential that future cases of nephrogenic systemic fibrosis are prevented

  4. Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

    DEFF Research Database (Denmark)

    Kellenberger, Terese; Marcussen, Niels; Nyengaard, Jens Randel

    2014-01-01

    Late renal graft loss is associated with interstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) is thought to facilitate fibrosis through interaction with TGF-β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate...... transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival...... was not significantly correlated to HIF-1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1-10-72-318-13)....

  5. Nephrogenic systemic fibrosis: late skin manifestations

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Marckmann, Peter; Rossen, Kristian

    2009-01-01

    BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadolinium-containing contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists...... and nephrologists recognize the disease. OBSERVATIONS: We studied 17 patients with NSF late in the disease. All patients showed epidermal atrophy and hairlessness of the affected regions, primarily the lower legs. Affected areas were symmetrically distributed and hyperpigmented in most cases. Eleven patients showed......: This descriptive case series of patients with NSF gives a detailed clinical picture of the skin manifestations late in the disease. It demonstrates that the clinical picture in the late stage has a varied presentation and that NSF has a significant effect on the quality of life....

  6. Current status of nephrogenic systemic fibrosis

    International Nuclear Information System (INIS)

    Daftari Besheli, L.; Aran, S.; Shaqdan, K.; Kay, J.; Abujudeh, H.

    2014-01-01

    Nephrogenic systemic fibrosis (NSF) occurs in patients with advanced chronic kidney disease (CKD) or acute renal failure, most commonly following exposure to gadolinium-based contrast agents (GBCAs). NSF can be debilitating and associated with increased mortality. The putative association of NSF with GBCAs prompted the development of guidelines to limit the use of these contrast agents in at-risk patients. Indeed, the incidence of NSF has decreased dramatically following application of these guidelines, which appears to be the only effective means of decreasing NSF incidence. Thus, increasing clinician awareness of these updated guidelines is important. The present review introduces and compares updated guidelines for GBCA use and discusses the latest advances in the understanding of the pathogenic mechanisms and treatment of NSF

  7. Imaging findings in congenital hepatic fibrosis

    International Nuclear Information System (INIS)

    Akhan, Okan; Karaosmanoglu, Ali Devrim; Ergen, Bilge

    2007-01-01

    Congenital hepatic fibrosis (CHF) is a rare congenital multisystemic disorder, mostly inherited in autosomal recessive fashion, primarily affecting renal and hepatobiliary systems. Main underlying process of the disease is the malformation of the ductal plate, the embryological precursor of the biliary system, and secondary biliary strictures and periportal fibrosis ultimately leading to portal hypertension. The natural course of the disease is highly variable ranging from minimally symptomatic disease to true cirrhosis of the liver. However, in most patients the most common manifestations of the diseases that are related to portal hypertension, particularly splenomegaly and bleeding varices. Many other disease processes may co-exist with the disease including Caroli's disease, choledochal cysts and autosomal recessive polycystic kidney disease (ARPKD) reflecting the mulstisystemic nature of the disease. The associating biliary ductal disease led the authors to think that all these entities are a continuum and different reflections of the same underlying pathophysiological process. Although, conventional method of diagnosis of CHF is the liver biopsy the advent of imaging technologies and modalities, today, may permit the correct diagnosis in a non-invasive manner. Characteristic imaging features are generally present and recognition of these findings may obviate liver biopsy while preserving the diagnostic accuracy. In this article, it is aimed to increase the awareness of the practising radiologists to the imaging findings of this uncommon clinical disorder and trail the blaze for future articles relating to this issue

  8. Imaging findings in congenital hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Akhan, Okan [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)]. E-mail: akhano@tr.net; Karaosmanoglu, Ali Devrim [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey); Ergen, Bilge [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)

    2007-01-15

    Congenital hepatic fibrosis (CHF) is a rare congenital multisystemic disorder, mostly inherited in autosomal recessive fashion, primarily affecting renal and hepatobiliary systems. Main underlying process of the disease is the malformation of the ductal plate, the embryological precursor of the biliary system, and secondary biliary strictures and periportal fibrosis ultimately leading to portal hypertension. The natural course of the disease is highly variable ranging from minimally symptomatic disease to true cirrhosis of the liver. However, in most patients the most common manifestations of the diseases that are related to portal hypertension, particularly splenomegaly and bleeding varices. Many other disease processes may co-exist with the disease including Caroli's disease, choledochal cysts and autosomal recessive polycystic kidney disease (ARPKD) reflecting the mulstisystemic nature of the disease. The associating biliary ductal disease led the authors to think that all these entities are a continuum and different reflections of the same underlying pathophysiological process. Although, conventional method of diagnosis of CHF is the liver biopsy the advent of imaging technologies and modalities, today, may permit the correct diagnosis in a non-invasive manner. Characteristic imaging features are generally present and recognition of these findings may obviate liver biopsy while preserving the diagnostic accuracy. In this article, it is aimed to increase the awareness of the practising radiologists to the imaging findings of this uncommon clinical disorder and trail the blaze for future articles relating to this issue.

  9. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  10. Radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Shopova, V.; Salovsky, P.; Dancheva, V.

    2001-01-01

    The likelihood of toxic pulmonary lesions development as the result of radiation therapy for pulmonary carcinoma and breast cancer is discussed. Two possible forms of radiation induced changes are described, namely: classical radiation pneumonitis (RP) terminating with lung fibrosis circumscribed in the radiation zone, and sporadic RP giving rise to bilateral lymphatic alveolitis and manifestations outside the irradiation field. Attention is called to the fact that chemotherapy augments the risk of toxic lung damage occurrence. A number of markers for early RP diagnosis, including lactate dehydrogenase activity, KL-6, procollagen III, transforming growth factor β, C-reactive protein and partial oxygen pressure are listed. Therapeutic possibilities in coping with RP and pulmonary fibrosis are assayed. Apart from the standard therapeutic approach using corticosteroids and azatioprin, ideas are set forth concerning the application of some antioxidants, angiotensin converting enzyme inhibitors and γ-interferon. It is pointed out that radiation pneumonitis and pulmonary fibrosis treatment has an essential practical bearing on life expectancy and quality of life in a great number of cancer patients. (author)

  11. Radiotherapy of breast fibrosis

    International Nuclear Information System (INIS)

    Heibel, J.H.

    1979-01-01

    In a retrospective study radiotherapy of breast fibrosis in hormone-treated men with histologically confirmed prostate carcinoma was examined. 10 patients had received hormones even before irradiation, 113 obtained hormone administration only after irradiation. The objective size of the glandular body and the overall size of the breast were measured with a special method developed by the author. 46 patients indicated complaints. With hypertrophic mamma and hypertrophic mamilla in 67 examined patients, 127 different symptoms resulted in total. Four patients of the group who had obtained hormones before irradiation, suffered from subjective symptoms. It resulted that radiotherapy of breast fibrosis carried out during hormone treatment is no gynecomastia prophylaxis, that already existent mamma hypertrophies are irreversible, but that existent sensations were notably reduced within 6 months after irradiation therapy. These results indicate the necessity of a radiotherapy of the mamma fibrosis before the hormone treatment is begun. Particularly in cases of higher operative risks, also the possibility of preferring radiotherapy to mastectomy should be fully utilized, in view of adequate or even better therapeutic results. (orig./MG) [de

  12. Mechanisms Underlying Profibrotic Epithelial Phenotype and Epithelial-Mesenchymal Crosstalk

    DEFF Research Database (Denmark)

    Bialik, Janne Folke

    Tubulointerstitial fibrosis (TIF) is the final pathway through which chronic kidney disease progresses toward renal failure. Tubular injury is a key feature of TIF but the exact role of the epithelium remains a matter of debate. In vivo only a small subset of myofibroblasts (MFs) appears...

  13. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    -epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  14. Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

    Science.gov (United States)

    Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

    2012-12-01

    Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

  15. 99mTc DMSA scintigraphic findings in renal tuberculosis

    International Nuclear Information System (INIS)

    Moon, Tae Yong; Kim, Kun Il; Yoon, Chi Soon; Lee, Suck Hong; Kim, Byung Soo

    1993-01-01

    Evaluations of residual renal function and the therapeutic effectiveness in renal tuberculosis have largely been dependent on intravenous pyelogram or Contrast-CT scan, even though, exact renal functions are not evaluate with there methods. 99m Tc- DMSA is a radiopharmaceutical that is trapped in the functioning tubular cells of the kidney and therefore, quantitative renal function could be evaluated by insuring the counts of renal radioactivity and concomitant evaluation of renal morphology could be passable with the analog images of the radioactivity. The authors retrospectively analyzed 99mTc-DMSA scans of 75 kidneys of 67 patients with confirmed renal tuberculosis. We classified the morphologies of tuberculous kidneys as 6 types. We classified the morphologies of tuberculous kidneys as 6 types such as the type with small cortical defect, with parenchymal ulcerocavernous lesions, ulcerocavernous fistula to pelvis, mass-like defects, contracted kidney with ureter visualization, and the type with non visualization of kidney, corresponding to the characters of renal tuberculous pathogenesis with abscess formation, ulcerocavernous fistula, and fibrosis, and corresponding to the renal anatomy with parenchyma, and pelvocalyceal collecting system. Their mean residual renal functions measured with 99mTc-DMSA uptake rates were 19.0%,18.4%, 7.9%, 12%, 4.1%, 3.4% respectively

  16. Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with cystic fibrosis.

    Science.gov (United States)

    Kaskavage, Jillian; Sklansky, Daniel

    2012-07-01

    Adolescents with well-controlled cystic fibrosis, including good lung function and appropriate growth, commonly participate in competitive athletic activities. We present the case of an adolescent male with cystic fibrosis, hyponatremia, dehydration, and rhabdomyolysis after participating in football practice on a summer morning. The patient presented with severe myalgia and serum sodium of 129 mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive hydration with intravenous 0.9% saline resulted in clinical improvement with no renal or muscular sequelae. Health care providers need to educate patients with cystic fibrosis about maintaining adequate hydration and sodium repletion during exercise. Research is needed regarding the appropriate amount and composition of oral rehydration fluids in exercising individuals with cystic fibrosis, as the physiology encountered in these patients provides a unique challenge to maintaining electrolyte balance and stimulation of thirst.

  17. The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

    Science.gov (United States)

    Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

    2017-12-01

    In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

  18. Edema in renal diseases – current view on pathogenesis

    Directory of Open Access Journals (Sweden)

    Irina Bobkova

    2016-10-01

    Full Text Available Edema is a common complication of numerous renal disease. In the recent past several aspects of the pathophysiology of this condition have been elucidated. We herein present a case of nephrotic syndrome in a 30 year-old men. The discussion revolves around the following key questions on fluid accumulation in renal disease: 1. What is edema? What diseases can cause edema? 2. What are the mechanisms of edema in nephrotic syndrome?   2a. The “underfill” theory   2b. The “overfill” theory   2c. Tubulointerstitial inflammation   2d. Vascular permeability 3. What are the mechanisms of edema in nephritic syndrome? 4. How can the volume status be assessed in patients with nephrotic syndrome? 5. What are therapeutic strategies for edema management? 6. What are the factors affecting response to diuretics? 7. How can we overcome the diuretics resistance?   7a. Effective doses of loop diuretics   7b. Combined diuretic therapy   7c. Intravenous administration of diuretics   7d. Albumin infusions   7e. Alternative methods of edema management 8. Conclusion.

  19. Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways

    Science.gov (United States)

    Fanton d'Andon, Martine; Quellard, Nathalie; Fernandez, Béatrice; Ratet, Gwenn; Lacroix-Lamandé, Sonia; Vandewalle, Alain; Boneca, Ivo G.; Goujon, Jean-Michel; Werts, Catherine

    2014-01-01

    Background Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that may lead to renal failure and fibrosis. L. interrogans provoke an interstitial nephritis, but the induction of fibrosis caused by L. interrogans has not been studied in murine models. Innate immune receptors from the TLR and NLR families have recently been shown to play a role in the development and progression of tissue fibrosis in the lung, liver and kidneys under different pathophysiological situations. We recently showed that TLR2, TLR4, and NLRP3 receptors were crucial in the defense against leptospirosis. Moreover, infection of a human cell line with L. interrogans was shown to induce TLR2-dependent production of fibronectin, a component of the extracellular matrix. Therefore, we thought to assess the presence of renal fibrosis in L. interrogans infected mice and to analyze the contribution of some innate immune pathways in this process. Methodology/principal findings Here, we characterized by immunohistochemical studies and quantitative real-time PCR, a model of Leptospira-infected C57BL/6J mice, with chronic carriage of L. interrogans inducing mild renal fibrosis. Using various strains of transgenic mice, we determined that the renal infiltrates of T cells and, unexpectedly, TLR and NLR receptors, are not required to generate Leptospira-induced renal fibrosis. We also show that the iNOS enzyme, known to play a role in Leptospira-induced interstitial nephritis, also plays a role in the induction of renal fibrosis. Conclusion/significance To our knowledge, this work provides the first experimental murine model of sustained renal fibrosis induced by a chronic bacterial infection that may be peculiar, since it does not rely on TLR or NLR receptors

  20. Imaging from cystic fibrosis

    International Nuclear Information System (INIS)

    Schmidt, H.; Posselt, H.G.

    2008-01-01

    Cystic fibrosis (CF) is the most frequent metabolic disorder with autosomal recessive inheritance in the Caucasian population. The gene defect is located on the long arm of chromosome 7. In Germany today, the actual median survival is 37 years. The genetic defect caused by chloride anion disturbances affects multiple body systems but the morbidity and mortality is due to lung disease. The secretion of highly viscous mucus promotes viral and bacterial pulmonary infections leading to airway obstruction and consecutive destruction of the lung parenchyma. This article will review and discuss both the clinical aspects of the disease and the diagnostic methods, referring in particular to new imaging strategies. (orig.)

  1. Renal candidiasis

    International Nuclear Information System (INIS)

    Khanna, S.; Malik, N.; Khandelwal, N.

    1990-01-01

    Most fungal infections of the urinary tract are caused by Candida albicans, a yeast-like saprophytic fungus which may become apathogen under various conditions which lower the host resistance. The use of computed tomography in the diagnosis of renal fungus balls is the subject of this communication with emphasis on the radiologists role in the recognition of this entity. (H.W.). 6 refs.; 2 figs

  2. Renal hemangioma

    Directory of Open Access Journals (Sweden)

    Theodorico F. da Costa Neto

    2004-06-01

    Full Text Available INTRODUCTION: Renal hemangioma is a relatively rare benign tumor, seldom diagnosed as a cause of hematuria. CASE REPORT: A female 40-year old patient presented with continuous gross hematuria, anemia and episodic right lumbar pain, with onset about 3 months previously. The patient underwent multiple blood transfusions during her hospital stay and extensive imaging propedeutics was performed. Semi-rigid ureterorenoscopy evidenced a bleeding focus in the upper calix of the right kidney, with endoscopic treatment being unfeasible. The patient underwent right upper pole nephrectomy and presented a favorable outcome. Histopathological analysis of the surgical specimen showed that it was a renal hemangioma. COMMENTS: Imaging methods usually employed for diagnostic investigation of hematuria do not have good sensitivity for renal hemangioma. However, they are important to exclude the most frequent differential diagnoses. The ureterorenoscopy is the diagnostic method of choice and endoscopic treatment can be feasible when the lesion is accessible and electrocautery or laser are available. We emphasize the open surgical treatment as a therapeutic option upon failure of less invasive methods.

  3. Histopathological retrospective study of canine renal disease in Korea, 2003~2008

    Science.gov (United States)

    Yhee, Ji-Young; Yu, Chi-Ho; Kim, Jong-Hyuk; Im, Keum-Soon; Chon, Seung-Ki

    2010-01-01

    Renal disease includes conditions affecting the glomeruli, tubules, interstitium, pelvis, and vasculature. Diseases of the kidney include glomerular diseases, diseases of the tubules and interstitium, diseases of renal pelvis, and developmental abnormalities. Renal tissue samples (n = 70) submitted to the Department of Veterinary Pathology of Konkuk University from 2003 to 2008 were included in this study. Tissue histopathology was performed using light microscopy with hematoxylin and eosin stains. Masson's trichrome, Congo Red, and Warthin starry silver staining were applied in several individual cases. Glomerular diseases (22.9%), tubulointerstitial diseases (8.6%), neoplastic diseases (8.6%), conditions secondary to urinary obstruction (24.3%), and other diseases (35.7%) were identified. Glomerulonephritis (GN) cases were classified as acute proliferative GN (5.7%), membranous GN (4.3%), membranoproliferative GN (4.3%), focal segmental GN (2.9%), and other GN (4.2%). The proportion of canine GN cases presently identified was not as high as the proportions identified in human studies. Conversely, urinary obstruction and end-stage renal disease cases were relatively higher in dogs than in human populations. PMID:21113095

  4. Successful pregnancy in a female patient with congenital chloride diarrhea (CLD) and renal impairment.

    Science.gov (United States)

    Shimizu, Yoshio; Kamoda, Tomohiro; Nagata, Michio; Yoh, Keigyo; Hashimoto, Yuko; Matsui, Akira; Yoshikawa, Hiroyuki; Yamagata, Kunihiro; Koyama, Akio

    2009-01-01

    We report a successful case of pregnancy in a female patient with congenital chloride diarrhea (CLD) and reduced renal function due to interruption of treatment. CLD is an autosomal recessive disorder of intestinal electrolyte absorption caused by mutations in the solute carrier family 26, member 3 (SLC26A3) gene, and continuous production of watery diarrhea induces dehydration, metabolic alkalosis and many kinds of electrolyte disturbances in CLD patients. The patient in our case was a 24-year-old female CLD patient with moderate renal impairment; a renal biopsy specimen showed minimal glomerular changes, but tubulointerstitial damage by crystal formation, consistent with renal function data. One year after our initial examination and reinstitution of therapy, the patient got married and soon conceived. There were no major problems during the course of pregnancy, and the patient successfully delivered a healthy full-term infant vaginally. The symptoms and clinical course of the patient were particularly mild, and we discuss possible reasons for these observations from a perspective of genotype, phenotype and environmental conditions.

  5. Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

    Directory of Open Access Journals (Sweden)

    Marcin Klapczynski

    2012-01-01

    Full Text Available Introduction: Surgical 5/6 nephrectomy and adenine-induced kidney failure in rats are frequently used models of progressive renal failure. In both models, rats develop significant morphological changes in the kidneys and quantification of these changes can be used to measure the efficacy of prophylactic or therapeutic approaches. In this study, the Aperio Genie Pattern Recognition technology, along with the Positive Pixel Count, Nuclear and Rare Event algorithms were used to quantify histological changes in both rat renal failure models. Methods: Analysis was performed on digitized slides of whole kidney sagittal sections stained with either hematoxylin and eosin or immunohistochemistry with an anti-nestin antibody to identify glomeruli, regenerating tubular epithelium, and tubulointerstitial myofibroblasts. An anti-polymorphonuclear neutrophil (PMN antibody was also used to investigate neutrophil tissue infiltration. Results: Image analysis allowed for rapid and accurate quantification of relevant histopathologic changes such as increased cellularity and expansion of glomeruli, renal tubular dilatation, and degeneration, tissue inflammation, and mineral aggregation. The algorithms provided reliable and consistent results in both control and experimental groups and presented a quantifiable degree of damage associated with each model. Conclusion: These algorithms represent useful tools for the uniform and reproducible characterization of common histomorphologic features of renal injury in rats.

  6. Obesity and renal hemodynamics

    NARCIS (Netherlands)

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

    2006-01-01

    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  7. Radiopharmaceuticals for renal studies

    International Nuclear Information System (INIS)

    Verdera, Silvia

    1994-01-01

    Between the diagnostic techniques using radiopharmaceuticals in nuclear medicine it find renal studies.A brief description about renal glomerular filtration(GFR) and reliability renal plasma flux (ERPF),renal blood flux measurement agents (RBF),renal scintillation agents and radiation dose estimates by organ physiology was given in this study.tabs

  8. The need for genetic study to diagnose some cases of distal renal tubular acidosis.

    Science.gov (United States)

    Heras Benito, Manuel; Garcia-Gonzalez, Miguel A; Valdenebro Recio, María; Molina Ordás, Álvaro; Callejas Martínez, Ramiro; Rodríguez Gómez, María Astrid; Calle García, Leonardo; Sousa Silva, Lisbeth; Fernández-Reyes Luis, María José

    We describe the case of a young woman who was diagnosed with advanced kidney disease, with an incidental finding of nephrocalcinosis of unknown aetiology, having been found asymptomatic throughout her life. The genetic study by panels of known genes associated with tubulointerstitial disease allowed us to discover autosomal dominant distal renal tubular acidosis associated with a de novo mutation in exon 14 of the SLC4A1 gene, which would have been impossible to diagnose clinically due to the advanced nature of the kidney disease when it was discovered. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Histochemical Analysis of Renal Dysplasia with Ureteral Atresia

    International Nuclear Information System (INIS)

    Kawate, Toyoko; Kawamura, Ryuki; Uchida, Takenori; Takahashi, Kyosuke; Hasegawa, Tomohiro; Futamata, Haruo; Katoh, Ryohei; Takeda, Sen

    2009-01-01

    Unilateral small kidney with ureteral obstruction was discovered in a 74-year-old female cadaver during an anatomical dissection course. In order to elucidate the histogenesis of renal dysplasia, we carried out histochemical and immunohistochemical analyses. On macroscopic view, the kidney was approximately 3 cm in length, 2 cm in width and weighed only 9 g. Although the ureter ran from the renal hilus to the bladder, its width was under 2 mm. The renal parenchyma was extremely thin and there was a large congested vein in the renal sinus. On microscopic examination of the kidney, we observed that numerous developing renal tubules had cytokeratin-positive epithelia, most of which were surrounded by concentric fibrosis. However, we could not detect any structures resembling the collecting duct, renal tubules, renal pelvis, or glomeruli. The concentric mesencymal fibrous tissue surrounding the immature renal tubules contained the smooth muscles that were positive for h-caldesmon. Serial sections of the ureter revealed several small and discontinuous lacunae lined by cuboidal and transitional epithelium, which did not constitute a patent lumen through the bladder. This case is a rare case of renal dysplasia with defect in recanalization of the ureteral bud during the early developmental stage

  10. Idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

    2017-02-23

    Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Renal histomorphology in dogs with pyometra and control dogs, and long term clinical outcome with respect to signs of kidney disease

    Directory of Open Access Journals (Sweden)

    Teige Jon

    2007-05-01

    Full Text Available Abstract Background Age-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature. Methods Dogs with pyometra were examined retrospectively for evidence of secondary renal damage and persisting renal disease through two retrospective studies. In Study 1, light microscopic lesions of renal tissue were graded and compared in nineteen dogs with pyometra and thirteen age-matched control bitches. In Study 2, forty-one owners of dogs with pyometra were interviewed approximately 8 years after surgery for evidence ofclinical signs of renal failure in order to document causes of death/euthanasia. Results Interstitial inflammation and tubular atrophy were more pronounced in dogs with pyometra than in the control animals. Glomerular lesions classified as glomerular sclerosis were present in both groups. No unequivocal light microscopic features of glomerulonephritis were observed in bitches in any of the groups. Two bitches severely proteinuric at the time of surgery had developed end stage renal disease within 3 years. In five of the bitches polyuria persisted after surgery. Most bitches did not show signs of kidney disease at the time of death/euthanasia. Conclusion Tubulointerstitial inflammation was observed, but glomerular damage beyond age-related changes could not be demonstrated by light microscopy in the dogs with pyometra. However, severe proteinuria after surgery may predispose to development of renal failure.

  12. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

    Directory of Open Access Journals (Sweden)

    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  13. Thoracic periaortal fibrosis and Ormond's disease

    International Nuclear Information System (INIS)

    Kacl, G.M.; Bino, M.; Salomon, F.; Risti, B.; Marincek, B.

    1995-01-01

    Two cases of thoracic periaortal fibrosis as a manifestation of retroperitoneal fibrosis (Ormond's disease) are shown on CT and MRI. Thoracic periaortal fibrosis can result in an inflammatory aneurysmo with chronic dissection. Manifestation of thoracic periaortal fibrosis may typically occur intermittently over decades. (orig.) [de

  14. [Plasma cell dyscrasias and renal damage].

    Science.gov (United States)

    Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

    2012-01-01

    Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

  15. Bilateral renal artery variation

    OpenAIRE

    Üçerler, Hülya; Üzüm, Yusuf; İkiz, Z. Aslı Aktan

    2014-01-01

    Each kidney is supplied by a single renal artery, although renal artery variations are common. Variations of the renal arteryhave become important with the increasing number of renal transplantations. Numerous studies describe variations in renalartery anatomy. Especially the left renal artery is among the most critical arterial variations, because it is the referred side forresecting the donor kidney. During routine dissection in a formalin fixed male cadaver, we have found a bilateral renal...

  16. Renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Džamić Zoran

    2016-01-01

    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  17. Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

    Science.gov (United States)

    Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

    2006-02-01

    The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

  18. Localized bilateral perirenal fibrosis, a rare cause of idiopathic retroperitoneal fibrosis

    Directory of Open Access Journals (Sweden)

    Maja Kveder

    2014-08-01

    Full Text Available Background: Idiopathic retroperitoneal fibrosis is an infrequent process of unknown aetiology characterised by fibrous tissue proliferation in the retroperitoneum. Even less frequent is a localized form of this disease by a proliferation of fibrous tissue around single or both kidneys.Case report: We describe a case of 46-year old man in whom medical management was started for accidentally discovered arterial hypertension, which turned out to be difficult to control.   During diagnostic work-up of hypertension, an abdominal ultrasound was obtained a year later demonstrating slight bilateral caliectasis without obvious visible cause for it. Laboratory exams have shown significantly impaired renal function, normocytic anaemia, slightly higher sedimentation rate, increased CRP and normal urinalysis. Nephrologist has decided for hospitalisation during which magnetic resonance imaging was performed  showing a few mm wide tissue coats surrounding both kidneys with fluid lying between the coat and kidney capsule. A biopsy of perirenal mass has confirmed a dense cellular lesion consisted of interweaved fascicles of spindle-shaped cells. After exclusion of tumours and other causes, a diagnosis of retroperitoneal fibrosis was confirmed. Clinical picture and laboratory data corresponded to idiopathic form of this disease. A treatment with tamoxifen was started after patient refused treatment with methylprednisolone. During tamoxifen monotherapy, there was gradual significant improvement of general symptoms, notable decline in inflammation markers, improvement of anaemia, normalisation of kidney function, and normalisation of blood pressure. Conclusion: Retroperitoneal fibrosis is still an obscure and multifaceted disease. A proper selection of diagnostic methods is the key to correct and fast diagnosis as well as good grounding for proper treatment.

  19. Metabolic alkalosis with multiple salt unbalance: an atypical onset of cystic fibrosis in a child

    Directory of Open Access Journals (Sweden)

    Dimitri Poddighe

    2017-12-01

    Full Text Available Dehydration with multiple salt abnormalities is frequently encountered in the paediatric emergency department, during acute illnesses complicated by loss of body fluids. Metabolic alkalosis is not a common finding in dehydrated children. The presence of unusual electrolyte unbalance, such as metabolic alkalosis, hyponatremia, hypochloremia and hypokalemia, without evidence of renal tubular defects, is named as pseudo-Bartter syndrome. It can occur in several clinical settings and, in infancy, it is described as a potential complication of cystic fibrosis. We report a case of pseudo-Bartter syndrome representing the onset of cystic fibrosis in childhood.

  20. Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

    Science.gov (United States)

    Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

    2017-08-01

    Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

  1. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...... selection, anatomical and physiological effects of RDN as well as possible beneficial effects on other diseases with increased sympathetic activity. The long awaited Symplicity HTN-3 (2014) results illustrated that the RDN group and the sham-group had similar reductions in BP. SUMMARY: Initial studies...

  2. Renal papillary necrosis

    Science.gov (United States)

    ... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

  3. Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka.

    Science.gov (United States)

    Nanayakkara, Shanika; Senevirathna, S T M L D; Parahitiyawa, Nipuna B; Abeysekera, Tilak; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Hitomi, Toshiaki; Kobayashi, Hatasu; Harada, Kouji H; Koizumi, Akio

    2015-09-01

    The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis. The objective of the present study is to use whole-exome sequencing to identify the genetic variants associated with CKDu. Whole-exome sequencing of eight CKDu cases and eight controls was performed, followed by direct sequencing of candidate loci in 301 CKDu cases and 276 controls. Association study revealed rs34970857 (c.658G > A/p.V220M) located in the KCNA10 gene encoding a voltage-gated K channel as the most promising SNP with the highest odds ratio of 1.74. Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome. Three out of four variants in LAMB2 were novel variants found exclusively in cases. Genetic investigations provide strong evidence on the presence of genetic susceptibility for CKDu. Possibility of presence of several rare variants associated with CKDu in this population is also suggested.

  4. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  5. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

    Directory of Open Access Journals (Sweden)

    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  6. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

    Full Text Available It was generally believed that Cystic fibrosis (CF is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR gene. Thirty-six patients (36% had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%, failure to thrive in 27 (75%, steatorrhea in 24 (66.7%, and hepatobiliary involvement in 5 (13.9%. Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8% patients, 8 (25% were homozygous, 14 (43.8% were heterozygous, and 10 (31.3% tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

  7. Radiotherapy and pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Sone, S; Miyata, Y; Tachiiri, H [Osaka Univ. (Japan). Faculty of Medicine

    1975-04-01

    Clinical findings of radiation pneumonitis and pulmonary fibrosis were outlined, and the relationship between occurence of these disorders and radiotherapy, clinical findings and X-ray picture were studied. Standard radiation dose as cell lethal response of carcinoma of the lung were 4,500 to 5,500 rad in 4 to 5.5 weeks in undifferentiated carcinoma, 6,000 to 7,000 rad in 6 to 7 weeks in squamous cell carcinoma, 7,000 to 9,000 rad in 7 to 9 weeks in adenocarcinoma, 4,500 to 5,000 rad in 4 to 5 weeks in the large sized cancer of the esophagus, 6,500 to 7,000 rad in 5 to 7 weeks in the small sized cancer of the esophagus, and irradiation of these amount of dose caused hazards in pulmonary function. Pathological and clinical findings of pulmonary hazards within 6 month period after irradiation, factors causing them and changes in X-ray pictures before and after irradiation were observed and discussed in clinical cases: the case of breast cancer in which 3,000 R/6 times/18 days of 5.5 MeV Liniac electron was irradiated to the chest wall, and the case of pulmonary cancer in which 5,000 rad/25 times/34 days of 6 MeV Liniac X-ray was irradiated in opposite 2 ports radiation beam treatment. The former revealed alveolar lesion and interlobular pleuritis at 4 month later, and remarkable lesion of pulmonary fibrosis was followed at 9 month after radiotherapy. The later developed radiation pneumonitis 1 month after radiotherapy, of which lesion extended to the upper part by 3 months later, and cancer recurred 6.5 month later.

  8. Renal calculus

    CERN Document Server

    Pyrah, Leslie N

    1979-01-01

    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  9. Fructokinase activity mediates dehydration-induced renal injury.

    Science.gov (United States)

    Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

    2014-08-01

    The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

  10. Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

    Science.gov (United States)

    Ma, Hongge; Qiao, Shupei; Wang, Zeli; Geng, Shuai; Zhao, Yufang; Hou, Xiaolu; Tian, Weiming; Chen, Xiongbiao; Yao, Lifen

    2017-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses. Copyright © 2017 the American Physiological Society.

  11. Nephrogenic systemic fibrosis: Review of 408 biopsy-confirmed cases

    Directory of Open Access Journals (Sweden)

    Zhitong Zou

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF has now been virtually eliminated by the discovery of its association with gadolinium-based contrast agents (GBCAs and the consequent reduced use of GBCA-enhanced magnetic resonance imaging (MRI in severe renal failure patients. This review of 408 biopsy-confirmed cases shows how to minimize NSF risk when performing GBCA-enhanced MRI or magnetic resonance angiography. The absence of any NSF cases in patients less than 8 years old or greater than 87 years old suggests that infants and elderly patients are already protected. Limiting GBCA dose to a maximum of 0.1 mMol/kg, dialyzing dialysis patients quickly following GBCA administration, delaying administration of GBCA in acute renal failure until after renal function returns or dialysis is initiated, and avoiding nonionic linear GBCA in renal failure patients, especially when there are pro-inflammatory conditions, appear to have reduced NSF risk to the point where safe GBCA-enhanced MRI is possible in most patients.

  12. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  13. TRANSPLANTE RENAL

    Directory of Open Access Journals (Sweden)

    Soraia Geraldo Rozza Lopes

    2014-01-01

    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  14. Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats.

    Science.gov (United States)

    Mori, Takefumi; Cowley, Allen W

    2004-04-01

    Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.

  15. Seguimiento del perfil proteico urinario en el trasplante renal

    OpenAIRE

    Facio, María Laura; Madalena, Leticia; Bacqué, María del Carmen; Idiarte, Laura; Pandolfo, Marcela; Angerosa, Margarita; Alejandre, Mariel; Fraind, Susana; Bresciani, Pablo; Pizzolato, Marco

    2010-01-01

    La nefropatía crónica del trasplante (NCT) se caracteriza por fibrosis intersticial y atrofia tubular, pero su etiología es diversa. El objetivo del trabajo fue evaluar el seguimiento cualitativo de proteínas urinarias en pacientes con más de seis años de trasplante renal y compararlo con parámetros de laboratorio y con biopsia renal. Se evaluaron 17 pacientes durante un año, a través de creatinina sérica, proteinuria y fraccionamiento proteico por electroforesis en geles de poliacrilamida (S...

  16. Two Case Reports and Actual Treatment Approachs of Retroperitoneal Fibrosis

    Directory of Open Access Journals (Sweden)

    Eymen Gazel

    2013-06-01

    Full Text Available Retroperitoneal fibrosis (RPF is a rare disease of unclear etiology, which is characterized by a chronic non specific inflammation of the retroperitoneum. This inflammation of the retroperitoneum may entrap and obstruct retroperitoneal structures, particularly the ureters. Patients with RPF show non specific clinical symptoms, including poorly localized back pain, general malaise, weight loss, anemia, features of renal failure and occasionally, mild fever. The early symptoms are non specific and an accurate diagnosis is often achieved only subsequent to urological obstruction or the occurrence of renal failure. Although a number of scientific journals devoted to RPF are present in the litera¬ture, there is no accepted diagnostic or therapeutic strategy for this disease. However, there are several therapeutic strate¬gies which have been proven to be effective. Hereby, we reported two cases of retroperitoneal fibrosis which had similar symptoms and findings but different responses to medical treatment .We aimed to discuss challanges of RPF%u2019s diagnosis and the treatment protocol.

  17. Idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Noble Paul W

    2008-03-01

    Full Text Available Abstract Idiopathic pulmonary fibrosis (IPF is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000 than in women (13.2/100,000. The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock. IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP. The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis, forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational exposures. IPF is typically progressive and leads to significant

  18. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  19. Breakdown in Breathing: The Complexities of Cystic Fibrosis

    Science.gov (United States)

    ... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact Sheet Genetic and Rare Diseases Information ...

  20. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  1. BILATERAL DUPLICATION OF RENAL ARTERIES

    OpenAIRE

    Prajkta A Thete; Mehera Bhoir; M.V.Ambiye

    2014-01-01

    Routine dissection of a male cadaver revealed the presence of bilateral double renal arteries. On the right side the accessory renal artery originated from the abdominal aorta just above the main renal artery. On the left side the accessory renal artery originated from the abdominal aorta about 1 cm above the main renal artery. Knowledge of the variations of renal vascular anatomy has importance in exploration and treatment of renal trauma, renal transplantation, renal artery embolization, su...

  2. Diffusion-Weighted Magnetic Resonance Imaging in Renal Lesion Characterization

    Directory of Open Access Journals (Sweden)

    Elif Karadeli

    2012-03-01

    Conclusion: The technique has the advantage that it is non-invasive without need for gadolinium administration, takes about 2 minute. This method provides qualitative and quantitative infomation on tissue characterization. DA-MRI and ADC values are important for characterization of renal lesions. Especially, utility of diffusion-weighted magnetic resonance imaging in the patients with risk for nephrogenic systemic fibrosis (NSF could be beneficial. [Cukurova Med J 2012; 37(1: 27-36

  3. Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2).

    Science.gov (United States)

    Xu, Zheng; Li, Weixin; Han, Jibo; Zou, Chunpeng; Huang, Weijian; Yu, Weihui; Shan, Xiaoou; Lum, Hazel; Li, Xiaokun; Liang, Guang

    2017-03-21

    Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2 -/- mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.

  4. An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka.

    Science.gov (United States)

    Nanayakkara, Shanika; Senevirathna, S T M L D; Abeysekera, Tilak; Chandrajith, Rohana; Ratnatunga, Neelakanthi; Gunarathne, E D L; Yan, Junxia; Hitomi, Toshiaki; Muso, Eri; Komiya, Toshiyuki; Harada, Kouji H; Liu, Wanyang; Kobayashi, Hatasu; Okuda, Hiroko; Sawatari, Hideyuki; Matsuda, Fumihiko; Yamada, Ryo; Watanabe, Takao; Miyataka, Hideki; Himeno, Seiichiro; Koizumi, Akio

    2014-01-01

    Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha-1 microglobulin in urine. None of 18 metals measured (μg//) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75-80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 × 10(-9) in quantitative trait locus analysis; p=3.73 × 10(-9) in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy male population suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.

  5. Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

    Science.gov (United States)

    Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

    2018-01-10

    Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

  6. A comparative kinetic RT/-PCR strategy for the quantitation of mRNAs in microdissected human renal biopsy specimens.

    Science.gov (United States)

    Del Prete, D; Forino, M; Gambaro, G; D'Angelo, A; Baggio, B; Anglani, F

    1998-01-01

    Molecular biology techniques, to be applicable to a diagnostic renal biopsy specimen, should (1) be highly sensitive to be performed on a very small quantity of tissue; (2) be quantitative because they have to analyze genes normally expressed in the tissue and (3) allow the analysis of as large a number of genes as possible. Among different methods, only the reverse-transcriptase polymerase chain reaction (RT/-PCR) might comply with previous requisites, but the few RT/-PCR examples on renal biopsies in the literature do not allow starting RNA quantification and quality control; furthermore they have the drawback of analyzing only few genes. In an ongoing study to assess the expression of a number of genes in glomeruli and in tubulointerstitium of patients with different nephropathies, we developed a comparative RT/-PCR kinetic strategy based on the purification and quantification of total glomerular and tubulointerstitial RNA and on the use of an internal standard, the housekeeping gene G3PDH. We demonstrate that in microdissected diagnostic renal biopsies (1) glomerular and interstitial starting RNA can be quantified; (2) the G3PDH gene may be used both as an internal standard and as an indirect marker of RNA integrity; (3) as low as 28 ng of total RNA is sufficient to obtain PCR products of eight genes, and (4) it is worth to operate on microdissected biopsy specimens because of the different expression of genes in the two renal compartments.

  7. CRYPTOCOCCUS NEOFORMANS VAR. GRUBII-ASSOCIATED RENAL AMYLOIDOSIS CAUSING PROTEIN-LOSING NEPHROPATHY IN A RED KANGAROO (MACROPUS RUFUS).

    Science.gov (United States)

    Thurber, Mary Irene; Gjeltema, Jenessa; Sheley, Matthew; Wack, Ray F

    2017-09-01

    A 10-year-old male castrated red kangaroo (Macropus rufus) presented with mandibular swelling. Examination findings included pitting edema with no dental disease evident on examination or radiographs. The results of blood work were moderate azotemia, hypoalbuminemia, and severely elevated urine protein:creatinine ratio (9.9). Radiographs showed an interstitial pattern of the caudal right lung, and an abdominal ultrasound demonstrated scant effusion. Symptomatic and empirical therapy with antibiotics, anti-inflammatory drugs, and an angiotensin-converting enzyme (ACE) inhibitor did not resolve clinical signs. Due to poor prognosis and declining quality of life, euthanasia was elected. Necropsy revealed chronic granulomatous pneumonia of the caudal right lung lobe with intralesional Cryptococcus, identified as C. neoformans var. grubii by DNA sequencing. Severe bilateral glomerular and tubulointerstitial amyloidosis induced protein-losing nephropathy, leading to tri-cavitary effusion, subcutaneous edema, and cachexia. The authors speculate that renal amyloidosis was associated with chronic cryptococcal pneumonia in this red kangaroo.

  8. Fibrosis imaging : Current concepts and future directions

    NARCIS (Netherlands)

    Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

  9. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

  10. Computed tomography of cystic pancreatic fibrosis

    International Nuclear Information System (INIS)

    Brachlow, M.; Zaunbauer, W.; Haertel, M.

    1984-01-01

    The computer tomographic appearances of atrophic and lipomatous degeneration of the pancreas in cystic pancreatic fibrosis are described. CT exploration of the pancreas in recommended, particularly in differential diagnostic aspects of cystic fibrosis. (orig.) [de

  11. Rapid decline in 51Cr-EDTA measured renal function during the first weeks following lung transplantation

    DEFF Research Database (Denmark)

    Hornum, M.; Iversen, M.; Steffensen, I.

    2009-01-01

    We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis/bronchiect......We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis....../bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the (51)Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12...

  12. Indications and results of renal biopsy in children: a 36-year experience.

    Science.gov (United States)

    Santangelo, Luisa; Netti, Giuseppe Stefano; Giordano, Paolo; Carbone, Vincenza; Martino, Marida; Torres, Diletta Domenica; Rossini, Michele; Di Palma, Anna Maria; Gesualdo, Loreto; Giordano, Mario

    2018-04-01

    This study was conducted to investigate retrospectively the indications for renal biopsy (RB) in native kidneys and to analyze pathological findings in a single tertiary pediatric hospital in Southern Italy for the last 36 years. All patients who underwent RB at our hospital from 1979 to 2014 were included. All renal tissue specimens were studied under light and immunofluorescent microscopy, while electron microscopy was performed only for specific clinical indications. The study group included 213 patients (female 43.2%) who underwent 225 percutaneous native kidney biopsies. Median age was 10.4 years (range 0.6-24 years). The most frequent indication for RB was nephrotic syndrome (44.4%), followed by proteinuria (27.6%), asymptomatic hematuria (17.3%) and acute kidney injury (9.8%). Gross hematuria appeared after biopsy in less than 5% of the patients, but none of them needed blood transfusion. Adequate renal tissue sample was obtained in 95.5% of the renal biopsies. Primary glomerulonephritis (GN) was the most common finding (61.4%), followed by secondary GN (21.4%), tubulointerstitial diseases (3.7%) and hereditary nephropathy (2.8%), while in 10.7% of the cases, normal renal tissues were found. According to histopathological diagnosis, the most common causes of primary GN were IgA nephropathy (20.9%), followed by minimal change disease (18.1%) and focal segmental glomerulosclerosis (11.6%). The epidemiology of glomerular disease in our single-center cohort is similar to that shown in other national and international reports. Moreover, our study shows that percutaneous ultrasound-guided RB is a safe, reliable and effective technique in children.

  13. Radionuclide evaluation of renal transplants

    International Nuclear Information System (INIS)

    Yang Hong; Zhao Deshan

    2000-01-01

    Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

  14. Distal renal tubular acidosis

    Science.gov (United States)

    ... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

  15. Early Posttransplant Isolated v1 Lesion Does Not Need to Be Treated and Does Not Lead to Increased Fibrosis

    Directory of Open Access Journals (Sweden)

    Irfan Moinuddin

    2016-01-01

    Full Text Available Acute vascular rejection (AVR is characterized by intimal arteritis in addition to tubulitis and interstitial inflammation. It is associated with a poorer prognosis compared to tubulointerstitial rejection (AIR and AVR is associated with a higher rate of graft loss than AIR. The prognosis and treatment of arteritis without tubulitis and interstitial inflammation (isolated v1 lesion are still controversial. We report a case of a patient who had a biopsy of the kidney allograft for evaluation of slow graft function. The biopsy revealed an isolated v1 lesion. However, we chose not to augment immunosuppression. The patient’s kidney allograft function improved over time with close monitoring. Repeat biopsy a year later showed no evidence of endothelialitis and relatively unchanged fibrosis and no other abnormalities. Although it is suggested that most cases of isolated v1 lesions will respond to corticosteroids or T cell depleting therapies, some cases will improve with conservative management. Further studies are needed to determine which cases could be managed conservatively.

  16. Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

    Science.gov (United States)

    Chade, Alejandro R; Kelsen, Silvia

    2010-08-01

    Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

  17. Radiation pericarditis and myocardial fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Westerhof, P W; van der Putte, S C.J.

    1976-06-01

    The case of a 45-yr-old man with constrictive pericarditis due to radiation for Hodgkin's disease is described. After pericardiectomy the clinical condition did not improve. At necropsy an extensive fibrosis of the myocardium especially located in the anterior part of the heart was found. The clinical consequences of this finding with respect to surgical treatment are briefly discussed.

  18. Hepatic fibrosis: Concept to treatment.

    Science.gov (United States)

    Trautwein, Christian; Friedman, Scott L; Schuppan, Detlef; Pinzani, Massimo

    2015-04-01

    Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases. Copyright © 2015. Published by Elsevier B.V.

  19. [Genetic counseling in cystic fibrosis].

    Science.gov (United States)

    Julia, S; Bieth, E

    2000-08-01

    Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

  20. Cardio-renal syndrome

    OpenAIRE

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  1. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  2. Nephrogenic systemic fibrosis after application of gadolinium-based contrast agents - a status paper

    International Nuclear Information System (INIS)

    Heinrich, M.; Uder, M.

    2007-01-01

    Recently the association of a rare disease named ''nephrogenic systemic fibrosis'' (NSF) with the administration of gadolinium-containing contrast media, especially gadodiamide (Omniscan, GE-Healthcare), was described. NSF is a scleroderma-like disease characterised by widespread tissue fibrosis. Until now, NSF cases were observed only in patients with kidney disease. Almost all patients were suffering from chronic renal insufficiency, 90 % of them required renal replacement therapy. The true incidence of the disease is unknown. First retrospective analyses of selected collectives of patients with end-stage renal disease showed 2 - 5 % cases of NSF after administration of Gadolinium-containing contrast agents with an odds ratio of 20 - 50 in comparison to non-exposed controls. NSF is a serious adverse reaction, which may result in severe disabilities and even death. Therefore all radiologists applying gadolinium-based contrast agents should be informed about this disease and the recent recommendations for its prevention. On the basis of the published data, Omniscan should not be used in patients with severe renal impairment (GFR 2 ) and those who have had or are undergoing liver transplantation. In neonates and infants up to 1 year of age, Omniscan should only be used after careful consideration. Also the other gadolinium-based contrast agents should be used in high-risk patients only after careful consideration using the lowest dose possible

  3. Traumatic renal infarction

    International Nuclear Information System (INIS)

    Yashiro, Naobumi; Ohtomo, Kuni; Kokubo, Takashi; Itai, Yuji; Iio, Masahiro

    1986-01-01

    Four cases of traumatic renal artery occlusion were described and illustrated. In two cases, direct blows to the abdomen compressed the renal artery against the vertebral column. Clinically, they were severely injured with macroscopic hematuria. Aortograms showed abrupt truncation of renal arteries. In the other two, rapid deceleration caused sudden displacement of the kidney producing an intimal tear with resultant thrombosis. Although they showed little injury without macrohematuria, aortograms revealed tapered occlusion of renal arteries. One of them developed hypertension. ''Rim sign'' of post-contrast CT and hypertension resulted from traumatic renal artery occlusion were reviewed. (author)

  4. Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model.

    Directory of Open Access Journals (Sweden)

    Flávio Teles

    Full Text Available The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP, in the 5/6 renal ablation model (Nx. Adult male Wistar rats underwent Nx and were divided into untreated (Nx and RP-treated (Nx+RP groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

  5. End-stage renal disease in both husband and wife in Taiwan.

    Science.gov (United States)

    Chang, C-H; Fang, Y-W; Chen, H-S

    2009-10-01

    The incidence and prevalence of end-stage renal disease (ESRD) are extremely high in Taiwan. It is an interesting fact that both the husband and wife in some families of Taiwan suffer from ESRD. Therefore, we attempted to identify the potential risk factors of such couples. This is a retrospective observational study. Six couples receiving maintenance dialysis in our hospital from 1996 to 2006 were enrolled in this study. Detailed medical history; drugs history including over-the-counter drugs (OCD), analgesics and herbal remedies; occupational history and onset of transitional cell carcinoma (TCC) were recorded. These data are correlated with pre-dialysis laboratory findings. The outcomes of dialysis and TCC were also recorded and analyzed. Two males were Chinese herbal medicine practitioners. All the patients (12/12) had taken Chinese herbs and most of them (10/12) had also taken OCD (especially cold remedies and analgesics). We found all of them had bilateral contracted kidneys, mild proteinuria and trace glucosuria. One patient's renal biopsy revealed Chinese herb nephropathy. Four patients (33%) suffered from TCC. Three patients expired during follow up due to hyperkalemia, extensive TCC and suicide, respectively. The prevalence of Chinese herbs or compound analgesics abuse is high in couples with ESRD. The clinical features and high incidence of TCC are compatible with drug related chronic tubulointerstitial nephritis. Abuse of offending agents should be considered as a risk factor in family members with ESRD.

  6. Cinacalcet versus Parathyroidectomy in the Treatment of Secondary Hyperparathyroidism Post Renal Transplantation.

    Science.gov (United States)

    Soliman, Amin R; Maamoun, Hoda A; Soliman, Mahmoud A; Darwish, Hatem; Elbanna, Esam

    2016-09-01

    Persistent hyperparathyroidism (HPT) with hypercalcemia is prevalent after transplant and is considered a risk factor for progressive bone loss and fractures and vascular calcification, as well as the development of tubulointerstitial calcifications of renal allografts and graft dysfunction. The subtotal parathyroidectomy is the standard treatment, although currently it has been replaced by the calcimimetic cinacalcet. The hypothesis of this study is that subtotal parathyroidectomy is superior to cinacalcet for treatment of persistent secondary parathyroidectomy post renal transplant, with minimal morbidity and significantly it reduces the cost of treatment after transplantation. We report our long-term clinical experience with either cinacalcet or parathyroidectomy in 59 kidney transplant recipients with hyperparathyroidism. Group one included medical treatment with cinacalcet and had 45 patients while parathyroidectomy patients (group 2) were 16 patients with two of them excluded because of surgical failure. No difference was found between groups for any parameter. A greater short-term change of calcium and phosphorus homeostasis obtained by surgery than by cinacalcet, and in long term change, no significant difference between the two groups. The main findings of this study are that correction of severe hyperparathyroidism was similar in both surgical and cinacalcet groups with the absence of a difference of long-term serum iPTH 1-84 levels between the two groups.

  7. Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

    2016-12-01

    Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

  8. Fractional excretion of beta-2-microglobulin in the urine of patients with normal or reduced renal function and hepatic coma

    DEFF Research Database (Denmark)

    Hansen, P B; Dalhoff, K; Joffe, P

    1991-01-01

    The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m...... excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were...... to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died...

  9. Protein S is protective in pulmonary fibrosis.

    Science.gov (United States)

    Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

    2016-08-01

    Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

  10. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

    Directory of Open Access Journals (Sweden)

    Yan Qiang

    2012-01-01

    Full Text Available Abstract Objective To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Methods Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5 years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0 were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. Results The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. Conclusion There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. Virtual slides The virtual slide(s for this article can be found here: http

  11. Prevalence of patients receiving renal replacement therapy in El Salvador in 2014.

    Science.gov (United States)

    García-Trabanino, Ramón; Trujillo, Zulma; Colorado, Ana Verónica; Magaña Mercado, Salvador; Henríquez, Carlos Atilio

    El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. To determine the RRT prevalence in El Salvador and some basic characteristics. The association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. National RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. Despite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands). Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Retroperitoneal fibrosis: the clinical and radiological manifestation

    International Nuclear Information System (INIS)

    Pan Weidong; Zhao Rongguo; Qin Mingwei; Xue Huadan; Liang Jixiang

    2005-01-01

    Objective: To analyze the clinical and radiological features of retroperitoneal fibrosis (RPF), and to deepen the understanding of this unusual disease and improve the diagnostic level at the early stage. Methods: Fourteen cases (10 males and 4 females, mean age 45.8 years) of pathologically diagnosed RPF from January 1990 to June 2004 were summarized. The clinical and radiological performance of the cases were analyzed. All patients received non-contrast CT scanning, 10 of them underwent enhanced CT scanning as well. 8 patients received MRI, 10 patients received IVP examination, and 11 received B-ultrasound. Results: (1) The very first symptoms usually included back pain, bellyache (10 cases), or urinary tract obstruction (3 cases), with increase of ESR, IgG, CRP value and abnormal renal function. (2) The result of radiological examination showed that 11 lesions of the 14 cases located at retroperitoneum. Ten cases were mass type and 4 cases were diffuse type. Non-contrast CT scanning revealed soft tissue mass at retroperitoneum with in homogenous or homogenous density. After contrast medium injection the lesions were enhanced with different extent. MRI results showed that the lesions presented low signal in T 1 WI, while in T 2 WI the signals had no obvious coherence but were different from one case to another. Conclusion: Radiological examination is one of the important methods for diagnosis of RPF. Based on the different characteristics of RPF in CT and MRI, together with the clinical findings, we will get valuable references for staging and follow-up of RPF. (authors)

  13. Epidemiology of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Ley B

    2013-11-01

    Full Text Available Brett Ley, Harold R Collard Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA Abstract: Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence and public health impact (ie, health care costs and resource utilization. Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. Keywords: idiopathic pulmonary fibrosis, epidemiology, incidence, prevalence, mortality, risk factors

  14. MRI in mucoviscidosis (cystic fibrosis)

    International Nuclear Information System (INIS)

    Eichinger, M.; Puderbach, M.; Kauczor, H.-U.; Heussel, C.-P.

    2006-01-01

    Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function. (orig.) [de

  15. [Historical compilation of cystic fibrosis].

    Science.gov (United States)

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  16. Fibrosis endomiocárdica

    Directory of Open Access Journals (Sweden)

    María Juliana Rodríguez-González

    2017-07-01

    Una de las formas más comunes de miocardiopatía restrictiva es la fibrosis endomiocárdica la cual es endémica en algunas zonas tropicales especialmente en África (países de bajos ingresos, pero en nuestro medio hay pocos reportes de aparición. Su etiología es desconocida, aunque existen diversos mecanismos que han sido involucrados en su fisiopatología. Su diagnóstico se basa en estudios imagenológicos (ecocardiograma transtorácico y resonancia magnética nuclear cardíaca. El pronóstico es muy pobre, y usualmente se diagnostica en etapas muy avanzadas de la enfermedad. Se describe el caso de una paciente femenina, adulta media, que debutó con cardiopatía restrictiva, cuyo diagnóstico final fue fibrosis endomiocárdica.

  17. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

    NARCIS (Netherlands)

    Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

    These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

  18. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, S; Daijo, K; Okabe, T; Kawamura, J; Hara, A [Kyoto Univ. (Japan). Hospital

    1979-08-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1.

  19. sup(99m)Tc-DMSA renal scintigraphy in renal failure due to various renal diseases

    International Nuclear Information System (INIS)

    Hosokawa, Shin-ichi; Daijo, Kazuyuki; Okabe, Tatsushiro; Kawamura, Juichi; Hara, Akira

    1979-01-01

    Renal contours in renal failure were studied by means of sup(99m)Tc-dimercaptosuccinic acid (DMSA) renoscintigraphy. Renal cortical images were obtained even in renal failure cases. Causes of renal failure were chronic glomerulonephritis in 7, bilateral renal tuberculosis in 2, chronic pyelonephritis in 3, bilateral renal calculi in 3, diabetic nephropathy in 2, polycystic kidney disease in 2 and stomach cancer in 1. (author)

  20. Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

    Directory of Open Access Journals (Sweden)

    Duarte M.E.L.

    2002-01-01

    Full Text Available Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha, IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha and transforming growth factor-ß (TGF-ß using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

  1. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  2. Anorexia nervosa in cystic fibrosis.

    Science.gov (United States)

    Linkson, Lynette; Macedo, Patricia; Perrin, Felicity M R; Elston, Caroline M

    2018-03-01

    This article explores the challenges associated with diagnosing and managing eating disorders such as anorexia nervosa amongst adolescents and adults with cystic fibrosis. It reviews the known risk factors, generic verses disease specific eating disorder risk screening tools and considers the ethical dilemmas associated with critically low body mass indices. A case review is included to illustrate the complexities of managing both conditions in the context of declining respiratory function. Copyright © 2017. Published by Elsevier Ltd.

  3. Idiopathic pulmonary fibrosis: treatment update.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-11-01

    Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF.

  4. Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

    Directory of Open Access Journals (Sweden)

    Cristina Espinosa-Díez

    2018-04-01

    Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

  5. Pathogenic mechanism in lung fibrosis

    International Nuclear Information System (INIS)

    Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

  6. Oral submucous fibrosis: an update

    Directory of Open Access Journals (Sweden)

    Wollina U

    2015-04-01

    Full Text Available Uwe Wollina,1 Shyam B Verma,2 Fareedi Mukram Ali,3 Kishor Patil4 1Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany; 2Nirvana Skin Clinic, Vadodara, Gujarat, India; 3Departments of Oral and Maxillofacial Surgery, SMBT Dental College, Sangamner, Maharashtra, India; 4Departments of Oral Pathology and Microbiology, SMBT Dental College, Sangamner, Maharashtra, India Abstract: Oral submucous fibrosis (OSF is a premalignant condition caused by betel chewing. It is very common in Southeast Asia but has started to spread to Europe and North America. OSF can lead to squamous cell carcinoma, a risk that is further increased by concomitant tobacco consumption. OSF is a diagnosis based on clinical symptoms and confirmation by histopathology. Hypovascularity leading to blanching of the oral mucosa, staining of teeth and gingiva, and trismus are major symptoms. Major constituents of betel quid are arecoline from betel nuts and copper, which are responsible for fibroblast dysfunction and fibrosis. A variety of extracellular and intracellular signaling pathways might be involved. Treatment of OSF is difficult, as not many large, randomized controlled trials have been conducted. The principal actions of drug therapy include antifibrotic, anti-inflammatory, and antioxygen radical mechanisms. Potential new drugs are on the horizon. Surgery may be necessary in advanced cases of trismus. Prevention is most important, as no healing can be achieved with available treatments. Keywords: betel nut, betel quid, oral disease, squamous cell carcinoma, tobacco, fibrosis

  7. Cystic Fibrosis-Related Diabetes

    Directory of Open Access Journals (Sweden)

    Kayani Kayani

    2018-02-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD, which affects 40–50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

  8. Imaging of renal osteodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jevtic, V. E-mail: vladimir.jevtic@mf.uni-lj.si

    2003-05-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  9. Imaging of renal osteodystrophy

    International Nuclear Information System (INIS)

    Jevtic, V.

    2003-01-01

    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination

  10. Otorhinolaryngologic manifestations of cystic fibrosis: literature review

    Directory of Open Access Journals (Sweden)

    Carvalho, Carolina Pimenta

    2008-12-01

    Full Text Available Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

  11. Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy.

    Science.gov (United States)

    Siamantouras, Eleftherios; Hills, Claire E; Squires, Paul E; Liu, Kuo-Kang

    2016-05-01

    Tubulointerstitial fibrosis represents the major underlying pathology of diabetic nephropathy where loss of cell-to-cell adhesion is a critical step. To date, research has predominantly focussed on the loss of cell surface molecular binding events that include altered protein ligation. In the current study, atomic force microscopy single cell force spectroscopy (AFM-SCFS) was used to quantify changes in cellular stiffness and cell adhesion in TGF-β1 treated kidney cells of the human proximal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the elastic modulus (stiffness) compared to control. Fluorescence microscopy confirmed that increased cell stiffness is accompanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrangement, affected the work of detachment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively demonstrate a correlation between cellular elasticity, adhesion and early morphologic/phenotypic changes associated with tubular injury. Diabetes affects many patients worldwide. One of the long term problems is diabetic nephropathy. Here, the authors utilized atomic force microscopy single cell force spectroscopy (AFM- SCFS) to study cellular stiffness and cell adhesion after TGF1 treatment in human proximal tubule kidney cells. The findings would help further understand the overall disease mechanism in diabetic patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia. Increasing evidence suggests that fibroblast growth factor (FGF21 has a crucial role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. METHODS: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight or streptozotocin (150 mg/kg to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. CONCLUSION: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

  13. Renal artery stenosis

    International Nuclear Information System (INIS)

    Desberg, A.; Paushter, D.M.; Lammert, G.K.; Hale, J.; Troy, R.; Novic, A.; Nally, J. Jr.

    1989-01-01

    Renal artery disease is a potentially correctable cause of hypertension. Previous studies have suggested the utility of duplex sonography in accurately detecting and grading the severity of renal artery stenosis. The purpose of this paper is to evaluate color flow Doppler for this use. Forty-three kidneys were examined by color-flow Doppler and conventional duplex sampling in patients with suspected renovascular hypertension or those undergoing aortography for unrelated reasons. Doppler tracings were obtained from the renal arteries and aorta with calculation of the renal aortic ratio (RAR) and resistive index (RI). Results of Doppler sampling with color flow guidance were compared with aortograms in a blinded fashion

  14. Incidental renal neoplasms

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

    2014-01-01

    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  15. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  16. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  17. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  18. Ciclosporin Does Not Influence Bone Marrow-Derived Cell Differentiation to Myofibroblasts Early after Renal Ischemia/Reperfusion

    NARCIS (Netherlands)

    Broekema, Martine; Harmsen, Martin C.; Koerts, Jasper A.; van Kooten, Theo G.; Uges, Donald R. A.; Petersen, Arjen H.; van Luyn, Marja J. A.; Navis, Gerjan; Popa, Eliane R.

    2009-01-01

    Background: Ischemia/reperfusion injury (IRI) is a risk factor for the development of interstitial fibrosis. Previously we had shown that after renal IRI, bone marrow-derived cells (BMDC) can differentiate to interstitial myofibroblasts. Here we hypothesized that the immunosuppressant ciclosporin A

  19. The Sociology and Entrenchment. A Cystic Fibrosis Test for Everyone?

    DEFF Research Database (Denmark)

    Koch, Lene; Stemerding, Dirk

    1994-01-01

    Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology......Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology...

  20. DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

    Science.gov (United States)

    Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

    2016-05-01

    Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

  1. Calcium Stone Growth in Urine from Cystic Fibrosis Patients and Healthy Controls

    Science.gov (United States)

    McSorley, Anita; Jones, Andrew M.; Webb, A. Kevin; Rao, P. Nagaraj; Kavanagh, John P.

    2007-04-01

    Cystic fibrosis patients have an increased risk of renal stone disease. There is some evidence that this may be related to a different excretory pattern of stone risk factors, but an alternative hypothesis, that the urine of cystic fibrosis patients is deficient in urinary inhibitors of crystallization and stone formation has not been tested. Here we have grown calcium stones, in vitro, in the presence of urine from healthy controls and compared this with growth in the presence of urine from cystic fibrosis patients. A stone farm was used to grow twelve calcium stones simultaneously, firstly in artificial urine for about 200 hours and then in 90% whole human urine for another 500 hours. Six of the stones received urine from healthy controls and six received urine from adult cystic fibrosis patients. There were no significant differences in stone mass at any of the key time points or in the overall growth pattern (p>0.05) between stones destined for, or treated with, urine from CF patients and the controls. Human urine greatly inhibited stone growth in vitro but there was no difference in the growth rate in urine from healthy controls and CF patients. This refutes the hypothesis that a tendency for a higher prevalence of urinary stones in CF patients is related to a deficiency in inhibitory activity.

  2. Fetal polycystic renal disease: prenatal sonographic findings with pathologic correlation

    International Nuclear Information System (INIS)

    Jun, Soon Ae; Park, Yong Hyun; Cha, Sun Hee; Kay, Jung Woong; Cho, Joo Yeon; Cha, Kwang Yul; Cha, Kyung Sub; Chi, Je G.

    1990-01-01

    Polycystic renal disease are congenital disorders, most of which are fatal in the postnatal period. A series of ten cases of polycystic renal disease diagnosed prenatally by ultrasonography is presented. Diagnostic criteria of ultrasonography for cystic renal disease are; 1. enlarge kidney (4 cases) 2. echogenic density of kidney (3 cases) 3. 0.4 - 0.9cm sized multiple cysts within the renal cortex (3 cases) 4. decreased amount of amniotic fluid (4 cases) 5. hydronephrosis (4 cases) 6. distended bladder (2 cases) 7. absence of bladder (2 cases) Eight of ten cases were confirmed by autopsy. Seven cases had other associated congenital anomalies, i.e. pulmonary hypoplasia (5), hepatic fibrosis (3), congenital heart disease (3), tracheoesophageal fistula with imperforate anus (1), caudal regression syndrome (1), Meckel-Gruber syndrome (1) and ambiguous genitalia (2). Additional cytogenetic study of the fetus and the careful family history taking followed by prenatal diagnosis of cystic renal disease. Precise prenatal diagnosis may allow patients the option of elective abortion or may prevent unnecessary obstetric intervention

  3. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  4. Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

    Science.gov (United States)

    Nabokov, A; Amann, K; Wagner, J; Gehlen, F; Münter, K; Ritz, E

    1996-03-01

    Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists

  5. Idiopathic pulmonary fibrosis: evolving concepts.

    Science.gov (United States)

    Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

    Science.gov (United States)

    Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

    2009-02-01

    Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

  7. Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway

    OpenAIRE

    Tian, Ya-Chung; Hung, Cheng-Chieh; Li, Yi-Jung; Chen, Yung-Chang; Chang, Ming-Yang; Yen, Tzung-Hai; Hsu, Hsiang-Hao; Wu, Mai-Szu; Phillips, Aled Owain; Yang, Chih-Wei

    2011-01-01

    Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The additio...

  8. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  9. Laparoscopic cholecystectomy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    McGrath, D S

    2012-02-03

    Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

  10. Genetics Home Reference: idiopathic pulmonary fibrosis

    Science.gov (United States)

    ... these health problems has idiopathic pulmonary fibrosis . Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms. In people with idiopathic pulmonary fibrosis , scarring of the lungs increases over time until the lungs can no longer ...

  11. Imaging pulmonary fibrosis; Imagerie des fibroses pulmonaires

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F. [Hopital Avicenne, 93 - Bobigny (France). Service de radiologie et de pneumologie

    2001-02-01

    Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

  12. Self-management education for cystic fibrosis.

    LENUS (Irish Health Repository)

    Savage, Eileen

    2011-01-01

    Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

  13. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, S.; Khalid, M; Elfaki, M.; Hassan, N.; Suliman, S.M.

    2007-01-01

    Background Hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatremia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective Renal function is profoundly influenced by thyroid status; the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and Patients In 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate (GFR) using modified in diet renal disease (MDRD) formula. Result In hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR Increased. The hypothyroid patients showed elevated serum creatinine levels (> 1.1mg/dl) compared to control group (p value .000). In patients mean estimated GFR decreased, compared to mean estimated GFR increased in the control group (p value= .002).

  14. Renal Function in Hypothyroidism

    International Nuclear Information System (INIS)

    Khalid, A. S; Ahmed, M.I; Elfaki, H.M; Hassan, N.; Suliman, S. M.

    2006-12-01

    Background hypothyroidism induces significant changes in the function of organ systems such as the heart, muscles and brain. Renal function is also influenced by thyroid status. Physiological effects include changes in water and electrolyte metabolism, notably hyponatraemia, and reliable alterations of renal hemodynamics, including decrements in renal blood flow, renal plasma flow, glomerular filtration rate (GFR). Objective renal function is profoundly influenced by thyroid status, the purpose of the present study was to determine the relationship between renal function and thyroid status of patients with hypothyroidism. Design and patients in 5 patients with primary hypothyroidism and control group renal functions are measured by serum creatinine and glomerular filtration rate(GFR) using modified in diet renal disease (MDRD) formula. Result in hypothyroidism, mean serum creatinine increased and mean estimated GFR decreased, compared to the control group mean serum creatinine decreased and mean estimated GFR increased. The hypothyroid patients showed elevated serum creatinine levels(>1.1 mg/d1) compared to control group (p value= 000). In patients mean estimated GFR increased in the control group (p value=.002).Conclusion thus the kidney, in addition to the brain, heart and muscle, is an important target of the action of thyroid hormones.(Author)

  15. Disappearing renal calculus.

    Science.gov (United States)

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-04-10

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging.

  16. Pulmonary complications of cystic fibrosis

    International Nuclear Information System (INIS)

    Ng, M.Y.; Flight, W.; Smith, E.

    2014-01-01

    The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF

  17. Liver manifestations of cystic fibrosis

    International Nuclear Information System (INIS)

    Akata, Deniz; Akhan, Okan

    2007-01-01

    Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

  18. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney.

    Science.gov (United States)

    Kelsen, Silvia; He, Xiaochen; Chade, Alejandro R

    2012-08-15

    Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution

  20. Abnormalities of the breast in chronic renal failure and renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Bae Young; Kim, Hak Hee; Choi, Kyu Ho; Park, Seog Hee [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2000-12-15

    Manifestations of breast abnormalities in these patients included breast calcifications, duct dilatation, fibrocystic change, rapidly enlarged multiple fibroadenomas, edema, invasive ductal cancer, extensive fibrosis, spontaneous hemorrhage, and Mondor's disease. These interesting cases we experienced are reported. Prolactin, growth hormone, and cortisol are required concurrently for normal development of mammary epithelium. Hormonal profile of chronic renal failure is different to normal person due to decreased renal clearance. The incidence of breast cancer is also increased in CRF. Metastatic soft tissue calcification is well described finding in chronic renal failure related to an increase in serum calcium phosphate product and secondary hyperparathyroidism. Kidney failure alone may increases prolactin level. The possibility of deranged hypothalamic-pituitary control mechanisms do not excluded. Impaired prolactin response to TRH stimulation has also been observed. Methyldopa and tricyclic antidepressants specifically were associated with hyperprolactinemia. Cyclosporin administration may elevate serum prolactin levels with simultaneous down regulation of prolactin receptors. Some populations of lymphocytes and fibroblasts exhibit cyclosporin receptors. Cyclosporin could potentially promote fibroadenomas by direct action, and seems to alter LH secretion.

  1. Abnormalities of the breast in chronic renal failure and renal transplantation

    International Nuclear Information System (INIS)

    Lee, Bae Young; Kim, Hak Hee; Choi, Kyu Ho; Park, Seog Hee

    2000-01-01

    Manifestations of breast abnormalities in these patients included breast calcifications, duct dilatation, fibrocystic change, rapidly enlarged multiple fibroadenomas, edema, invasive ductal cancer, extensive fibrosis, spontaneous hemorrhage, and Mondor's disease. These interesting cases we experienced are reported. Prolactin, growth hormone, and cortisol are required concurrently for normal development of mammary epithelium. Hormonal profile of chronic renal failure is different to normal person due to decreased renal clearance. The incidence of breast cancer is also increased in CRF. Metastatic soft tissue calcification is well described finding in chronic renal failure related to an increase in serum calcium phosphate product and secondary hyperparathyroidism. Kidney failure alone may increases prolactin level. The possibility of deranged hypothalamic-pituitary control mechanisms do not excluded. Impaired prolactin response to TRH stimulation has also been observed. Methyldopa and tricyclic antidepressants specifically were associated with hyperprolactinemia. Cyclosporin administration may elevate serum prolactin levels with simultaneous down regulation of prolactin receptors. Some populations of lymphocytes and fibroblasts exhibit cyclosporin receptors. Cyclosporin could potentially promote fibroadenomas by direct action, and seems to alter LH secretion.

  2. Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

    Science.gov (United States)

    Kelsen, Silvia; Hall, John E; Chade, Alejandro R

    2011-07-01

    Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

  3. Bilateral triple renal arteries

    International Nuclear Information System (INIS)

    Pestemalci, Turan; Yildiz, Yusuf Zeki; Yildirim, Mehmet; Mavi, Ayfer; Gumusburun, Erdem

    2009-01-01

    Knowledge of the variations of the renal artery has grown in importance with increasing numbers of renal transplants, vascular reconstructions and various surgical and radio logic techniques being performed in recent years. We report the presence of bilateral triple renal arteries, discovered on routine dissection of a male cadaver. On the right side, one additional renal artery originated from the abdominal aorta (distributed to superior pole of the kidney) and one other originated from the right common iliac artery (distributed to lower pole of the kidney). On the left side, both additional renal arteries originated from the abdominal aorta. Our observation has been compared with variations described in the literature and their clinical importance has been emphasized. (author)

  4. Radiology of renal failure

    International Nuclear Information System (INIS)

    Griffiths, H.J.

    1990-01-01

    This book covers most aspects of imaging studies in patients with renal failure. The initial chapter provides basic information on contrast agents, intravenous urography, and imaging findings in the urinary tract disorders responsible for renal failure and in patients who have undergone transplantation. It illustrates common gastro-intestinal abnormalities seen on barium studies in patients with renal failure. It illustrates the cardiopulmonary complications of renal failure and offers advice for radiologic differentiation. It details different aspects of skeletal changes in renal failure, including a basic description of the pathophysiology of the changes; many excellent illustrations of classic bone changes, arthritis, avascular necrosis, and soft-tissue calcifications; and details of bone mineral analysis

  5. [Hypertension and renal disease

    DEFF Research Database (Denmark)

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.

    2009-01-01

    Renal mechanisms, in particular the renin-angiotensin system and renal salt handling, are of major importance in blood pressure regulation. Co-existence of hypertension and decreased renal function may be due to nephrosclerosis secondary to hypertension, or primary renal disease with secondary...... hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...... nephropathy, effective blood pressure lowering is of paramount importance, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers are agents of choice Udgivelsesdato: 2009/6/15...

  6. Compromiso renal en pacientes HIV+ Renal abnormalities in HIV infected patients

    Directory of Open Access Journals (Sweden)

    María Marta Pernasetti

    2010-06-01

    agents and/or drugs. Little is known about the prevalence of renal diseases that may occur as a complication of or related to HIV infection in asymptomatic patients. This is a single center cross-sectional study of asymptomatic HIV+ patients referred to a nefrology care service at an Argentine hospital to look for the presence of renal abnormalities. Fifty two consecutive patients were studied between April and November 2008. Patients underwent plasma and urine analysis, ultrasound, and kidney biopsy as needed. Mean age was 39.9 ± 10.6 years, 88% were male, time from HIV diagnosis 53.2 ± 41.2 months (2-127; 71% had HIV-disease and 77% were on antiretroviral therapy. Mean plasma HIV-RNA copies number was 7.043 ± 3.322 and CD4+ cell count: 484 ± 39. Pathologic findings in urine analysis were present in 30.7% of patients: albuminuria 16.6%, microscopic hematuria 11.5%, hypercalciuria 10.8% and crystalluria 6%. Mean glomerular filtration rate was 102.2 ± 22.95 ml/min (34-149 and 41% of patients could be classified in stages 1 to 3 of chronic kidney disease. Renal abnormalities prevaled in older patients without relationship with presence of HIV-disease. Two patients were biopsied and the findings included: tubulointerstitial nephritis with presence of crystal deposition in one and IgA nephropathy in the other. No HIV-associated nephropathy was detected. The broad spectrum and the high prevalence of lesions found in this series suggest that asymptomatic HIV-infected patients should routinely undergo renal evaluation.

  7. Tuberculosis of the genitourinary system-Urinary tract tuberculosis: Renal tuberculosis-Part II

    International Nuclear Information System (INIS)

    Merchant, Suleman; Bharati, Alpa; Merchant, Neesha

    2013-01-01

    This article reviews the computed tomography and magnetic resonance imaging (MRI) features of renal tuberculosis (TB), including TB in transplant recipients and immunocompromised patients. Multi detector computed tomography (MDCT) forms the mainstay of cross-sectional imaging in renal TB. It can easily identify calcification, renal scars, mass lesions, and urothelial thickening. The combination of uneven caliectasis, with urothelial thickening and lack of pelvic dilatation, can also be demonstrated on MDCT. MRI is a sensitive modality for demonstration of features of renal TB, including tissue edema, asymmetric perinephric fat stranding, and thickening of Gerota's fascia, all of which may be clues to focal pyelonephritis of tuberculous origin. Diffusion-weighted MR imaging with apparent diffusion coefficient (ADC) values may help in differentiating hydronephrosis from pyonephrosis. ADC values also have the potential to serve as a sensitive non-invasive biomarker of renal fibrosis. Immunocompromised patients are at increased risk of renal TB. In transplant patients, renal TB, including tuberculous interstitial nephritis, is an important cause of graft dysfunction. Renal TB in patients with HIV more often shows greater parenchymal affection, with poorly formed granulomas and relatively less frequent findings of caseation and stenosis. Atypical mycobacterial infections are also more common in immunocompromised patients

  8. Clinical role of non-contrast magnetic resonance angiography for evaluation of renal artery stenosis

    International Nuclear Information System (INIS)

    Utsunomiya, Daisuke; Nomitsu, Yohei; Komeda, Yosuke; Okigawa, Takashi; Urata, Joji; Miyazaki, Mitsue; Yamashita, Yasuyuki

    2008-01-01

    The association between a gadolinium-based contrast material and nephrogenic systemic fibrosis has been discussed. The purpose of our study was to evaluate whether non-contrast enhanced magnetic resonance angiography (MRA) might provide sufficient information of renal artery stenosis. The non-contrast MRA of 26 patients with hypertension was retrospectively reviewed in the present study. The significant renal artery stenosis was visually evaluated by comparing non-contrast MRA with computed tomography or conventional angiographic finding. Difference of the intensities between the proximal and distal aorta was quantitatively evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of non-contrast MRA in the evaluation of the renal artery stenosis was 78%, 91%, 64% and 96%, respectively. The distal abdominal aorta showed less signal intensity than the proximal aorta by 16.9±12.2%. Non-contrast MRA is a non-invasive and effective method that allows evaluation of the renal artery stenosis. (author)

  9. Postinjection Muscle Fibrosis from Lupron

    Directory of Open Access Journals (Sweden)

    Erica Everest

    2015-01-01

    Full Text Available We describe the case of a 6.5-year-old girl with central precocious puberty (CPP, which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate Depot-Ped (3 months intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

  10. Drug-induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Daba, Mohammad H.; Al-Arifi, Mohammad N; Gubar, Othman A.; El-Tahir, Kamal E.

    2004-01-01

    Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta Tbgf-beta, PDGF, If-I, Et-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspne a, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example Il-I beta and TNF-alpha via activation of nuclear transcription factor Nf-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages and lymphocytes phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system. (author)

  11. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF)

    Energy Technology Data Exchange (ETDEWEB)

    Turkbey, Baris; Choyke, Peter L. [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); Ocak, Iclal [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Daryanani, Kailash [National Institutes of Health, Clinical Center, Department of Radiology, Bethesda, MD (United States); Font-Montgomery, Esperanza; Lukose, Linda; Bryant, Joy; Tuchman, Maya; Gahl, William A. [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); Mohan, Parvathi [George Washington University, Department of Pediatric Gastroenterology, Washington, DC (United States); Heller, Theo [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Gunay-Aygun, Meral [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); National Institutes of Health, Intramural Program, Office of Rare Diseases, Office of the Directors, Bethesda, MD (United States)

    2009-02-15

    ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform dilatation of the renal collecting ducts leading to enlarged spongiform kidneys and ductal plate malformation of the liver resulting in congenital hepatic fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the kidney and liver. Imaging plays an important role in the diagnosis and follow-up of ARPKD/CHF. Combined use of conventional and high-resolution US with MR cholangiography in ARPKD/CHF patients allows detailed definition of the extent of kidney and hepatobiliary manifestations without requiring ionizing radiation and contrast agents. (orig.)

  12. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    Porn, U.; Hahn, K.; Fischer, S.

    2003-01-01

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.) [de

  13. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  14. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    Science.gov (United States)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

  15. Cadmium and renal cancer

    International Nuclear Information System (INIS)

    Il'yasova, Dora; Schwartz, Gary G.

    2005-01-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine

  16. Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice.

    Science.gov (United States)

    Kim, In Hee; Xu, Jun; Liu, Xiao; Koyama, Yukinori; Ma, Hsiao-Yen; Diggle, Karin; You, Young-Hyun; Schilling, Jan M; Jeste, Dilip; Sharma, Kumar; Brenner, David A; Kisseleva, Tatiana

    2016-08-01

    We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFD-induced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between old-aged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or

  17. Recurrent urinary tract infection by burkholderia cepacia in a live related renal transplant recipient

    International Nuclear Information System (INIS)

    Zeshan, M.

    2012-01-01

    Burkholderia cepacia is high virulent organism usually causing lower respiratory tract infections especially in Cystic fibrosis (CF) patients and post lung transplant. Urinary tract infections with Burkholderia cepacia have been associated after bladder irrigation or use of contaminated hospital objects. Post renal transplant urinary tract infection (UTI) is the most common infectious complications. Recurrent urinary tract infection with Burkholderia cepacia is a rare finding. Complete anatomical evaluation is essential in case recurrent urinary tract infections (UTI) after renal transplant. Vesico-ureteric reflux (VUR) and neurogenic urinary bladder was found to be important risk factors. (author)

  18. Renal Branch Artery Stenosis

    DEFF Research Database (Denmark)

    Andersson, Zarah; Thisted, Ebbe; Andersen, Ulrik Bjørn

    2017-01-01

    Renovascular hypertension is a common cause of pediatric hypertension. In the fraction of cases that are unrelated to syndromes such as neurofibromatosis, patients with a solitary stenosis on a branch of the renal artery are common and can be diagnostically challenging. Imaging techniques...... that perform well in the diagnosis of main renal artery stenosis may fall short when it comes to branch artery stenosis. We report 2 cases that illustrate these difficulties and show that a branch artery stenosis may be overlooked even by the gold standard method, renal angiography....

  19. Renal artery stenosis.

    Science.gov (United States)

    Tafur-Soto, Jose David; White, Christopher J

    2015-02-01

    Atherosclerotic renal artery stenosis (RAS) is the single largest cause of secondary hypertension; it is associated with progressive renal insufficiency and causes cardiovascular complications such as refractory heart failure and flash pulmonary edema. Medical therapy, including risk factor modification, renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, is advised in all patients. Patients with uncontrolled renovascular hypertension despite optimal medical therapy, ischemic nephropathy, and cardiac destabilization syndromes who have severe RAS are likely to benefit from renal artery revascularization. Screening for RAS can be done with Doppler ultrasonography, CT angiography, and magnetic resonance angiography. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Cryoablation of Renal Angiomyolipoma

    DEFF Research Database (Denmark)

    Makki, Ahmad; Graumann, Ole; Hoyer, Soren

    2017-01-01

    BACKGROUND: Small series have reported that cryoablation (CA) is a safe and feasible minimally invasive nephron-sparing alternative for the treatment of renal angiomyolipomas (renal AMLs). The aim of the present study was to investigate the safety and efficacy of CA in patients with renal AML......-guided CA. The mean patient age was 46 years [interquartile range (IQR) 30] and the mean tumor volume was 50.1 cm(3) (IQR 53.3). In all cases, the procedure was effectively conducted with no conversion to open surgery, and no major complications were experienced. The mean follow-up time was 25 months (IQR...

  1. Viral infection drives tissue fibrosis in vitro

    Directory of Open Access Journals (Sweden)

    Andrea P. Malizia

    2008-04-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  2. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  3. Acute renal failure in children

    International Nuclear Information System (INIS)

    Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.

    1987-01-01

    Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

  4. Nanoparticles for the treatment of liver fibrosis

    Directory of Open Access Journals (Sweden)

    Poilil Surendran S

    2017-09-01

    Full Text Available Suchithra Poilil Surendran, Reju George Thomas, Myeong Ju Moon, Yong Yeon Jeong Department of Radiology, BioMolecular Theranostics (BiT Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH, South Korea Abstract: Chronic liver diseases represent a global health problem due to their high prevalence worldwide and the limited available curative treatment options. They can result from various causes, both infectious and noninfectious diseases. The application of nanoparticle (NP systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for chronic liver diseases. This review presents the pathogenesis, diagnosis and the emerging nanoparticulate systems used in the treatment of chronic liver diseases caused by liver fibrosis. Activated hepatic stellate cell (HSC is considered to be the main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A variety of nanoparticulate systems are mainly focused on targeting HSC in the treatment of hepatic fibrosis. As early liver fibrosis is reversible by current NP therapy, it is being studied in preclinical as well as clinical trials. Among various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their distinct properties to deliver drugs as well as other therapeutic moieties. Liposomal NPs in clinical trials is considered to be a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver fibrosis is updating fast, and hopefully, it can be the future remedy for liver fibrosis. Keywords: liver fibrosis, inorganic nanoparticles, liposomes, micelles

  5. Vitamin A supplementation for cystic fibrosis.

    Science.gov (United States)

    Bonifant, Catherine M; Shevill, Elizabeth; Chang, Anne B

    2014-05-14

    People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of

  6. Voice Disorder in Cystic Fibrosis Patients

    Science.gov (United States)

    Lourenço, Bruna Mendes; Costa, Kauê Machado; da Silva Filho, Manoel

    2014-01-01

    Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and suggest they may

  7. Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

    DEFF Research Database (Denmark)

    Pincikova, T; Nilsson, Kristine Kahr; Moen, I E

    2011-01-01

    Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

  8. "Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne Braae

    2011-01-01

    Background Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. Objectives To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients...... Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation...

  9. Combined Pulmonary Fibrosis and Emphysema Syndrome

    Science.gov (United States)

    Rounds, Sharon I. S.

    2012-01-01

    There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

  10. Transient elastography for liver fibrosis diagnosis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

    2008-01-01

    Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

  11. Transient elastography for liver fibrosis diagnosis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

    2009-01-01

    Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

  12. Cough in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Mirjam J.G. van Manen

    2016-09-01

    Full Text Available Many patients with idiopathic pulmonary fibrosis (IPF complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably “multifactorial” and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.

  13. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  14. Retroperitoneal fibrosis: findings with MR

    International Nuclear Information System (INIS)

    Martinez Rodrigo, J.; Marti-Bonnati, L.; Diago, T.; Ferrer, M.D.; Aleixandre, A.; Morote, V.

    1993-01-01

    Retroperitoneal fibrosis (RF) is an uncommon disease characterized by the presence of a chronic inflammatory reaction, with the formation of fibrous tissue that replaces the normal retroperitoneal tissue, trapping vessels and/or ureters. We present a retrospective review of 3 cases of idiopathic RF studied by means of ultrasound, CT scan and MR imaging, and we assess the features of the MR image, as well as its capacity for characterizing the lesion. We compare the findings obtained with 3 imaging techniques, describing the utility of each one, and their advantages and disadvantages in the assessment of this pathology. In MR, idiopathic RF appears as a hypodense mass in SET1, SE-T2 and STIR sequences. (Author) 9 ref

  15. Renal tumors in infancy

    International Nuclear Information System (INIS)

    Lucaya, J.; Garcia, P.

    1997-01-01

    The classification of childhood renal masses in updated, including the clinical signs and imaging techniques currently employed to confirm their presence and type them. Several bening and malignant childhood tumors are described in substantial detail. (Author) 24 refs

  16. Renal cell carcinoma

    Science.gov (United States)

    ... kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney tumor - CT scan Kidney metastases, CT scan Kidney - blood and urine flow References Campbell SC, Lane BR. Malignant renal tumors. In: Wein AJ, Kavoussi LR, Partin AW, ...

  17. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  18. [Small renal mass].

    Science.gov (United States)

    Prokofiev, D; Kreutzer, N; Kress, A; Wissing, F; Pfeifer, H; Stolzenburg, J-U; Dietel, A; Schwalenberg, T; Do, M; Truß, M C

    2012-10-01

    The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

  19. Common paediatric renal conditions

    African Journals Online (AJOL)

    Few children in South Africa have access to dialysis or renal transplantation, so it is important to .... the chronic administration of antibiotics increases the risk of a UTI with a resistant .... factors for recurrent urinary tract infection in young women.

  20. Renal and perirenal abscesses

    International Nuclear Information System (INIS)

    Patterson, J.E.; Andriole, V.T.

    1987-01-01

    Our knowledge of the spectrum of renal abscesses has increased as a result of more sensitive radiologic techniques. The classification of intrarenal abscess now includes acute focal bacterial nephritis and acute multifocal bacterial nephritis, as well as the previously recognized renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. In general, the clinical presentation of these entities does not differentiate them; various radiographic studies can distinguish them, however. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy are required for resolution. 73 references

  1. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...... associated with lithium treatment is suggested. This increased risk may, at least partly, be a result of surveillance bias. Additionally, the earliest studies pointed toward an increased risk of end-stage renal disease associated with lithium treatment, whereas the later and methodologically most sound...

  2. Renal dynamic scintigraphy in renal graft evaluation; Cintilografia renal dinamica na avaliacao do transplante renal

    Energy Technology Data Exchange (ETDEWEB)

    Cervo, Marco Antonio Cadorna; Amarante Junior, Jose Luiz de Medeiros; Souza, Ricardo Alberto Manhaes de; Evangelista, Maria Gardenia; Cavalcante, Carlos Alberto Provasi; Neder, Jacqueline de Roure e; Espinola, Ircania Jorge [Hospital Naval Marcilio Dias, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    1996-12-31

    The goal of this was to describe the use of the dynamic renal scintigraphy in patients grafted. The authors described the scintigraphy method utilised and results were discussed 8 refs., 9 figs., 1 tab.

  3. Spontaneous rupture of renal pelvis secondary to ureteral obstruction by urothelial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Daniel Alvarenga; Palma, Ana Laura Gatti; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago Jose; Caserta, Nelson Marcio Gomes, E-mail: daniel_alvafer@yahoo.com.br, E-mail: daniel_alvafer@icloud.com [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Medicina. Dept. de Radiologia

    2014-09-15

    Partial spontaneous rupture of the upper urinary tract is rare and usually associated with nephrolithiasis. Other reported causes, apart from instrumentation and trauma, involve obstructive ureteral tumor in the pelvic cavity, retroperitoneal fibrosis, fluid overload, and pregnancy. We report a case of spontaneous rupture of renal pelvis secondary to ureteral obstruction caused by urothelial tumor, clinically suspected and evaluated by CT scans and MRIs, discussing the relevant findings for diagnosis.(author)

  4. OBSTETRIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    Rajeshwari

    2015-11-01

    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  5. Renal artery pseudoaneurysm

    Directory of Open Access Journals (Sweden)

    Luiz Inácio Roman

    Full Text Available Abstract The renal artery pseudoaneurysm embody a rare vascular complication coming of percutaneous procedures, renal biopsy, nephrectomy, penetrating traumas and more rarely blunt traumas. The clinical can be vary according the patient, the haematuria is the symptom more commom. Is necessary a high level of clinical suspicion for your diagnosis, this can be elucidated by through complementary exams as the eco-color Doppler and the computed tomography scan (CT. This report is a case of a patient submitted a right percutaneous renal biopsy and that, after the procedure started with macroscopic haematuria, urinary tenesmus and hypogastric pain. The diagnosis of pseudoaneurysm was given after one week of evolution when the patient was hospitalized because gross haematuria, tachycardia, hypotension and hypochondrium pain. In the angiotomography revealed a focal dilation of the accessory right renal inferior polar artery, dilation of renal pelvis and all the ureteral course with presence hyperdenso material (clots inside the middle third of the ureter. The treatment for the majority of this cases are conservative, through arterial embolization, indicated for thouse of smaller dimensions in patients who are hemodynamically stable. However, it was decided by clinical treatment with aminocaproic acid 1 g, according to previous studies for therapy of haematuria. The patient received discharge without evidence of macroscopic haematuria and with normal renal ultrasound, following ambulatory care.

  6. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    Science.gov (United States)

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  7. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

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    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  8. Pengaruh Pemberian Valsartan Dan Kurkumin Terhadap Pembentukan Fibrosis Di Tubulus Proksimal Ginjal Akibat Obstruksi Ureter Unilateral pada Tikus Wistar.

    Directory of Open Access Journals (Sweden)

    Lubis M

    2013-01-01

    . Perbedaan bermakna terbentuKata kunci: Obstruksi ureter, Valsartan, Kurkumin, Fibrosis, Degenerasi hidrofilik, AtrofiAbstractIntroduction: ureter obstruction is a condition where is an obstacle for urine flow from renal to blast (vesica urinaria. The obstruction in ureter will decrease glomerulus filtration flow and it destroys renal parenchym. Fibroses in obstructed renal present through two mediators, there are necrotizing tumor factors-α (TNF-α and angiotension-II. Obstruction of this two mediators will decrease fibroses grading in proximal tubules of renal caused by obtruction. One of TNF-α inhibitors is curcumene and angiotension-II will be obstructed by valsartan. Methods: this experiment is kind of experimental type using animal experiment (Wistar Mice. Wistar Mice are divided into two groups, each group consist of 15 mice, so the total are 30 mice. This animals tighted with at proximal ureter The first group is control one, given valsartan. The second group is given valsartan and curcumene. Oral route and dilution before given. Medicine is given use 1 cc spuit. Giving action in 14 days. The fifteenth day, we take renal of Wistar and do histology examination. Significant difference between fibroses forming in proximal tubulus analyzed by Chi Square Statistic Test with correction of Yates and T-Test, beside that, hydofic degeneration and atrophy in proximal tubulus analyzed by T-Test Statistic Test. Result: there is significant difference in forming of fibroses in proximal tubules of renal between action group and controlled group (Chi Square with p ≤ 0.0001 and T-Test with p ≤ 0.000. In hydrophilic degeneration forming in proximal tubules gotten significant difference between two groups ( T-Test with p ≤ 0.000. In atrophy forming in proximal tubules, there is important difference between two groups (T-Test with p ≤ 0.000.Concultion. There is an effect in giving valsartan and curcumene to fibroses forming in proximal tubules of renal. There is significant

  9. Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury

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    Robert I. Menzies

    2017-05-01

    Full Text Available Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1 has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40 ml/min/1.73 sq. m., and increased interstitial fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells cultured under high glucose conditions. In mice, P2X7R-deficiency prevented glomerular macrophage attraction and collagen IV deposition; however, the more severe interstitial inflammation and fibrosis often seen in human diabetic kidney diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor (AZ11657312 can reduce renal macrophage accrual following the establishment of hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest that P2X7R activation may contribute to the high prevalence of kidney disease found in diabetics.

  10. BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.

    Science.gov (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Li, De-Tian; Du, Zhen-Xian; Wang, Hua-Qin; Wang, Yan-Qiu

    2015-01-01

    Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-β1. Forced overexpression of BAG3 selectively increased collagens. TGF-β1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

  11. Molecular and cellular mechanisms of pulmonary fibrosis

    Science.gov (United States)

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  12. Imaging findings in idiopathic pelvic fibrosis

    International Nuclear Information System (INIS)

    Wiesner, W.; Bongartz, G.; Stoffel, F.

    2001-01-01

    Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

  13. European Cystic Fibrosis Society Standards of Care

    DEFF Research Database (Denmark)

    Stern, Martin; Bertrand, Dominique Pougheon; Bignamini, Elisabetta

    2014-01-01

    Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful ...... to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.......Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful...... therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference...

  14. Liver Fibrosis: Current Principles of Diagnosis

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    A.K. Duda

    2014-09-01

    Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

  15. Imaging findings in idiopathic pelvic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Wiesner, W.; Bongartz, G. [Inst. of Diagnostic Radiology University Hospital Basel (Switzerland); Stoffel, F. [Inst. of Urology, University Hospital Basel (Switzerland)

    2001-04-01

    Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

  16. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

    Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients

  17. Drug- and radiation-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    Uthgenannt, H.

    1976-01-01

    These two forms of pulmonary fibrosis which according to their type have nothing to do with one another, are presented as they are well suited to clarify the problems of the diagnosis of pulmonary fibrosis which is not a fixed concept for the pathologists. The frequent discrepancy found between the subjective clinical symptoms, clinical findings and X-ray and morphological pictures is indicated. (MG) [de

  18. Festival food coma in cystic fibrosis.

    Science.gov (United States)

    Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

    2013-07-01

    Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

  19. Possible involvement of gadolinium chelates in the pathophysiology of nephrogenic systemic fibrosis: A critical review

    International Nuclear Information System (INIS)

    Idee, Jean-Marc; Port, Marc; Medina, Christelle; Lancelot, Eric; Fayoux, Emmanuelle; Ballet, Sebastien; Corot, Claire

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a recently described, highly debilitating scleroderma-like disease occurring in patients with severe or end-stage renal failure. NSF is characterized by cutaneous papules and coalescing plaques ('peau d'orange' appearance) and a wooden consistency. It may ultimately cause disabling contractures of several joints, thus making many patients wheelchair-dependent. NSF has been associated to prior administration of gadolinium chelates (GC) used as contrast agents for magnetic resonance imaging. The best available treatment option at the present time is renal transplantation. The mechanism of NSF has not been fully elucidated. Several hypotheses have been proposed so far and are critically discussed in the present review article. Gadolinium has been found in skin biopsy samples of patients. The most widely accepted hypothesis is related to dechelation of less stable GC, progressively releasing free Gd 3+ which may subsequently lead to the attraction of CD34+, CD45+, pro-collagen+ circulating fibrocytes via the release of chemokines, thereby inducing systemic fibrosing disorders. Pre-existing renal failure may facilitate the process by delaying the excretion of GC. A complex interplay between gadolinium and co-factors (pro-inflammatory status, vascular injury, high dose of erythropoietin, high levels of calcium, phosphorus, etc.) may occur in patients with impaired renal function. This and other hypotheses remain to be investigated, as well as the role and independence of co-factors

  20. Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

    Directory of Open Access Journals (Sweden)

    Honglei Guo

    2016-01-01

    Full Text Available Aldosterone (Aldo is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA, and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

  1. Automatic liver volume segmentation and fibrosis classification

    Science.gov (United States)

    Bal, Evgeny; Klang, Eyal; Amitai, Michal; Greenspan, Hayit

    2018-02-01

    In this work, we present an automatic method for liver segmentation and fibrosis classification in liver computed-tomography (CT) portal phase scans. The input is a full abdomen CT scan with an unknown number of slices, and the output is a liver volume segmentation mask and a fibrosis grade. A multi-stage analysis scheme is applied to each scan, including: volume segmentation, texture features extraction and SVM based classification. Data contains portal phase CT examinations from 80 patients, taken with different scanners. Each examination has a matching Fibroscan grade. The dataset was subdivided into two groups: first group contains healthy cases and mild fibrosis, second group contains moderate fibrosis, severe fibrosis and cirrhosis. Using our automated algorithm, we achieved an average dice index of 0.93 ± 0.05 for segmentation and a sensitivity of 0.92 and specificity of 0.81for classification. To the best of our knowledge, this is a first end to end automatic framework for liver fibrosis classification; an approach that, once validated, can have a great potential value in the clinic.

  2. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

    2017-01-01

    Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These

  3. Renal PTA stenting

    International Nuclear Information System (INIS)

    Tsetis, D.

    2012-01-01

    Full text: Renal artery stenosis (RAS) is a common condition that may lead to hypertension, progressive renal dysfunction and cardiovascular morbidity. Catheter-based therapy for symptomatic, haemodynamically significant, RAS has become the preferred method of revascularization. Balloon angioplasty has been the traditional treatment of choice for fibromuscular dysplasia, however stents are increasingly used for the treatment of atheromatous lesions; in many cases-such as in ostial lesions-, direct stenting is strongly indicated. Despite the increased use of endovascular therapy for renal artery stenosis, there is still controversy regarding the optimal management and the net benefit of this treatment. Several randomized trials of balloon angioplasty or stenting for renal artery stenosis compared with medical therapy alone have been conducted, however these could not show definite advantage of endovascular therapy. Problems encountered with those trials include enrollment of small number of patients, frequent crossover from medical to interventional therapy compromising the intention-to-treat results, or selection of patients that are not expected to show clear benefit. The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) is the most important of these trials; however, it,s study design was faulty and therefore did not provide conclusive evidence to answer the question of whether angioplasty and stenting or medical therapy is the best treatment for haemodynamically significant RAS. All expectations are now focused on the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial which was designed to answer the same question, and its methodologies took into consideration the weaknesses of the ASTRAL trial. Regarding stent device itself, it seems that the optimal design is probably a stainless steel, laser cut, open-cells stent mounted on a rapid exchange delivery balloon catheter compatible with 0.014-in and 0.018-in guidewire. As a future

  4. Renal scar formation and kidney function following antibiotic-treated murine pyelonephritis

    Directory of Open Access Journals (Sweden)

    Patrick D. Olson

    2017-11-01

    Full Text Available We present a new preclinical model to study treatment, resolution and sequelae of severe ascending pyelonephritis. Urinary tract infection (UTI, primarily caused by uropathogenic Escherichia coli (UPEC, is a common disease in children. Severe pyelonephritis is the primary cause of acquired renal scarring in childhood, which may eventually lead to hypertension and chronic kidney disease in a small but important fraction of patients. Preclinical modeling of UTI utilizes almost exclusively females, which (in most mouse strains exhibit inherent resistance to severe ascending kidney infection; consequently, no existing preclinical model has assessed the consequences of recovery from pyelonephritis following antibiotic treatment. We recently published a novel mini-surgical bladder inoculation technique, with which male C3H/HeN mice develop robust ascending pyelonephritis, highly prevalent renal abscesses and evidence of fibrosis. Here, we devised and optimized an antibiotic treatment strategy within this male model to more closely reflect the clinical course of pyelonephritis. A 5-day ceftriaxone regimen initiated at the onset of abscess development achieved resolution of bladder and kidney infection. A minority of treated mice displayed persistent histological abscess at the end of treatment, despite microbiological cure of pyelonephritis; a matching fraction of mice 1 month later exhibited renal scars featuring fibrosis and ongoing inflammatory infiltrates. Successful antibiotic treatment preserved renal function in almost all infected mice, as assessed by biochemical markers 1 and 5 months post-treatment; hydronephrosis was observed as a late effect of treated pyelonephritis. An occasional mouse developed chronic kidney disease, generally reflecting the incidence of this late sequela in humans. In total, this model offers a platform to study the molecular pathogenesis of pyelonephritis, response to antibiotic therapy and emergence of sequelae

  5. Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory-fibrosis through the NF-κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt.

    Science.gov (United States)

    Chen, Ye; Liang, Yuzhen; Hu, Tingting; Wei, Riming; Cai, Congjie; Wang, Ping; Wang, Lingyu; Qiao, Wei; Feng, Leping

    2017-11-01

    Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro , is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP-ribose) polymerase-1, NF-κB p65, forkhead box protein O1 and B-cell lymphoma 2-like protein 4 were also significantly increased at 96 h compared with control group (Pendogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (Pendogenous Nampt upregulation may be critical in the treatment of DN pro-inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.

  6. Nephrogenic systemic fibrosis: chronic imaging findings and review of the medical literature

    International Nuclear Information System (INIS)

    Weigle, Jeffrey P.; Broome, Dale R.

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder which has been strongly associated with exposure to gadolinium-based contrast media (GBCM) in the setting of renal insufficiency. Although this disorder primarily affects the skin, it can result in severe joint contractures, disabilities and even death. However, to date, there have been no published studies reporting chronic imaging findings of NSF. In this report we present three biopsy-proven cases of NSF with the associated chronic MRI, radiographic and bone scintigraphy findings. Two of the patients had been exposed to gadodiamide, and one had been exposed to gadopentetate dimeglumine prior to the onset of NSF. Two are newly reported cases. One patient's subacute imaging findings have previously been reported, but significant chronic images will now be presented. This patient became severely disabled from contractures and developed long bone smooth periosteal reaction, extensive intra-articular and periarticular calcifications, musculotendinous heterotopic ossification and ankylosis of several joints. One of the patients underwent renal transplantation 6 months after GBCM exposure, with near complete resolution of the skin fibrosis. The third patient had persistent MRI findings of skin thickening, with low T1 and high T2 signal intensity 5 years after exposure to gadodiamide. A review of the medical literature is provided, emphasizing the association of NSF with various GBCM. These cases broaden our understanding of the long-term imaging findings and complications of NSF and the stratified risk of NSF with various GBCM. (orig.)

  7. Gene therapy in cystic fibrosis.

    Science.gov (United States)

    Flotte, T R; Laube, B L

    2001-09-01

    Theoretically, cystic fibrosis transmembrane conductance regulator (CFTR) gene replacement during the neonatal period can decrease morbidity and mortality from cystic fibrosis (CF). In vivo gene transfers have been accomplished in CF patients. Choice of vector, mode of delivery to airways, translocation of genetic information, and sufficient expression level of the normalized CFTR gene are issues that currently are being addressed in the field. The advantages and limitations of viral vectors are a function of the parent virus. Viral vectors used in this setting include adenovirus (Ad) and adeno-associated virus (AAV). Initial studies with Ad vectors resulted in a vector that was efficient for gene transfer with dose-limiting inflammatory effects due to the large amount of viral protein delivered. The next generation of Ad vectors, with more viral coding sequence deletions, has a longer duration of activity and elicits a lesser degree of cell-mediated immunity in mice. A more recent generation of Ad vectors has no viral genes remaining. Despite these changes, the problem of humoral immunity remains with Ad vectors. A variety of strategies such as vector systems requiring single, or widely spaced, administrations, pharmacologic immunosuppression at administration, creation of a stealth vector, modification of immunogenic epitopes, or tolerance induction are being considered to circumvent humoral immunity. AAV vectors have been studied in animal and human models. They do not appear to induce inflammatory changes over a wide range of doses. The level of CFTR messenger RNA expression is difficult to ascertain with AAV vectors since the small size of the vector relative to the CFTR gene leaves no space for vector-specific sequences on which to base assays to distinguish endogenous from vector-expressed messenger RNA. In general, AAV vectors appear to be safe and have superior duration profiles. Cationic liposomes are lipid-DNA complexes. These vectors generally have been

  8. USO DEL TAMOXIFENO PARA TRATAMIENTO DE LA FIBROSIS SISTÉMICA NEFROGÉNICA

    Directory of Open Access Journals (Sweden)

    Enz PA

    2009-01-01

    Full Text Available La fibrosis sistémica nefrogénica (FSN es una entidad infrecuente, que se desarrolla en pacientes insuficientes renales en diálisis, vinculándose su etiopatogenia con diversos factores tales como el uso de gadolinio intravenoso, el antecedente de cirugías vasculares, etc.El Tamoxifeno, es un modulador selectivo (inhibición competitiva de los receptores estrogénicos, que posee propiedades antifibróticas las cuales se emplean para el tratamiento de entidades tales como: fibrosis retroperitoneal, esclerosis peritoneal asociada a diálisis peritoneal, tumores desmoides y en algunos casos de esclerodermia.En el presente articulo presentamos la hipótesis original de que el tamoxifeno, por su propiedades fibrinolíticas, podría ser una terapia no inmunosupresora potencialmente útil para el tratamiento de la fibrosis sistémica nefrogénica, evitándose desde ya su uso en pacientes portadores de contraindicaciones para recibirlo.

  9. Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

    LENUS (Irish Health Repository)

    Robb, W B

    2010-03-01

    The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine\\'s effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy.

  10. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient......, this has important therapeutic implications. The pathological sequence in renal stone formers with dRTA is discussed....

  11. Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Department of Pathology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050200, Hebei (China); Zhao, Xin [Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei (China); Chang, Yanzhong [Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei (China); Zhang, Yuanyuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Xi [Department of Pharmacy, The Forth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei (China); Zhang, Xuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Liu, Zhenyi; Guo, Hui [Department of Medicinal Chemistry, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Wang, Na [Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Gao, Yonggang [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Zhang, Jianping, E-mail: zhangjianping14@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Li, E-mail: chuli0614@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei (China)

    2016-06-15

    Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and

  12. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  13. Renal diagnosis of chronic hemodialysis patients with urinary tract transitional cell carcinoma in Taiwan.

    Science.gov (United States)

    Chang, Chung-Hsin; Yang, Cheng-Ming; Yang, An-Hang

    2007-04-15

    Transitional cell carcinoma (TCC) is the most common malignancy in dialysis patients of Taiwan. The reason for such a high incidence of TCC is undetermined. The correlation between the underlying renal disease and the development of TCC was investigated. The authors retrospectively reviewed the clinical data and outcome of 1537 chronic hemodialysis (HD) patients from 1993 to 2002. The incidence of TCC was computed. The Cox regression method was used to analyze the role of potential risk factors. After a mean dialysis duration of 46.5 months, 26 (1.69%) patients with TCC were diagnosed. The standardized incidence ratio (SIR) of TCC was 48.2 as compared with the general population and the SIR of TCC seemed higher in women (65.1) and in the age group 50 to 54 years (173.6). Of them, most cases showed no definite etiology. All these cases showed bilateral contracted kidneys. Nonnephrotic proteinuria was found in all cases and trace glucosuria was found in 17 (65%). Painless gross hematuria was the cardinal symptom and distant metastasis was rare. Also, TCC in upper urinary tracts were common and found in 14 (54%) of patients. Age at the time of dialysis, female sex, compound analgesic use, and Chinese herb use had statistical significance as risk factors (P Taiwan, especially in female and middle-aged patients. The study indicated that chronic tubulointerstitial nephritis (CTIN) is the most likely underlying renal disease in HD patients with TCC, a high percentage of the CTIN related to the usage of Chinese herbs or compound analgesics may contribute to the development of TCC, whereas diabetes or chronic glomerulonephritis play only a minor role.

  14. Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with progressive renal disease.

    Directory of Open Access Journals (Sweden)

    Oliver Jung

    2010-08-01

    Full Text Available Epoxyeicotrienoic acids (EETs are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH and sEH inhibitors are considered treatment for chronic renal failure (CRF. We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg, the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.

  15. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D

    2013-08-01

    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  16. Imaging chronic renal disease and renal transplant in children

    International Nuclear Information System (INIS)

    Carmichael, Jim; Easty, Marina

    2010-01-01

    At Great Ormond Street Hospital we have the highest number of paediatric renal transplant patients in Europe, taking cases from across the United Kingdom and abroad. Our caseload includes many children with rare complicating medical problems and chronic renal failure related morbidity. This review aims to provide an overview of our experience of imaging children with chronic renal failure and transplants. (orig.)

  17. Male fertility in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, S H

    2011-04-05

    Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16\\/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.

  18. Cystic fibrosis: a clinical view.

    Science.gov (United States)

    Castellani, Carlo; Assael, Baroukh M

    2017-01-01

    Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

  19. Pneumothorax and idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Iwasawa, Tae; Ogura, Takashi; Takahashi, Hiroshi; Asakura, Akira; Gotoh, Toshiyuki; Yazawa, Takuya; Inoue, Tomio

    2010-01-01

    We evaluated the relation between the severity of idiopathic pulmonary fibrosis (IPF) and the incidence of pneumothorax on computed tomography (CT) images. In this retrospective study, we evaluated the presence of pneumothorax in 56 consecutive patients who died of IPF from the initial CT to death. We quantitatively analyzed a total of 207 CT images and measured the volume of the normal pattern (N-pattern) and each lesion pattern on the initial CT and their serial changes. The effects of pneumothorax and clinical and CT features on survival were evaluated using Cox regression analysis. Pneumothorax occurred in 17 of 56 patients. Comparison of the pneumothorax (+) and (-) groups showed the initial vital capacity (VC) was lower (P=0.005) and the follow-up period was shorter (P=0.03) in the former group. The decrease in the N-pattern volume in the pneumothorax (+) group was significantly faster than in the pneumothorax (-) group (P=0.013). Cox regression analyses identified a rapid decrease in N-pattern volume (P=0.008) and a rapid decrease in VC (P=0.002), but not pneumothorax, as significant predictors of poor survival. Pneumothorax in IPF patients is associated with lower VC and rapid deterioration of CT findings. The findings suggest that pneumothorax is a complication of advanced IPF. (author)

  20. Liver Disease in Cystic Fibrosis: an Update

    Science.gov (United States)

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-01-01

    Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

  1. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie

    2014-01-01

    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

  2. [Renal colic in pregnancy].

    Science.gov (United States)

    Negru, Irina; Pricop, C; Costăchescu, Gh

    2010-01-01

    Renal colic in pregnant women is a serious condition, mainly when is associated with fever. Our retro-prospective study analyzes 111 cases managed conservatively or with endourological procedures for renal colic--insertion of JJ stents and percutaneous nephrostomy. Clinical evolution determined the insertion of JJ stents in 60 cases and the failure of this procedure imposed percutaneous nephrostomy in 5 cases. In 56 cases urinary tract infection was associated and in 2 cases, despite all efforts, the patients deceased due to sever sepsis. The immediate drainage of the upper urinary tract for renal colic in pregnancy is the recommended treatment, especially when the pain is associated with fever. JJ stens were well tolerated, even when they were replaced after 3 months. Pregnant women with a history of UTI or stone disease should be carefully followed-up.

  3. Renal cell karcinoma trial

    International Nuclear Information System (INIS)

    Werf-Messing, B. van der; Heul, R.O. van der; Ledeboer, R.C.

    1981-01-01

    A total of 174 patients underwent simple nephrectomy in case of clinically operable kidney cancer without demonstrable metastases. Of these 85 received preoperative irradiation to the kidney and the regional lymph nodes (3000-4000 rad in 3-4 weeks). Prognosis was not influenced by preoperative irradiation. The preoperatively assessable prognostic criteria were sex and sedimentation rate: ESR >= 30 and being male worsened prognosis. The clinical T-categories of the UICC were not related to prognosis. Of the microscopic examination of the nephrectomy specimen, renal vein invasion and to a lesser extent a low degree of differentiation appeared to worsen prognosis. The prognostic influence of the P-categories was caused by a higher incidence of renal vein involvement in case of higher P-category. The most important prognostic factors - ESR, renal vein involvement, and sex - were not interrelated. Elective chemotherapy, radiation therapy, and hormone therapy could be considered in certain high-risk groups. (orig.)

  4. Scintigraphy of renal transplant

    International Nuclear Information System (INIS)

    Ramackers, J.M.; Marrast, A.C.; Touraine, J.L.; Peyrin, J.O.

    1995-01-01

    Scintigraphy is useful for monitoring perfusion and function of renal transplant, as well as for diagnosing miscellaneous surgical. This non-invasive imaging technique, which uses no deleterious products, is an attractive alternative for patients. This is especially true for those patients in early post-transplant course, with immunity depression and often impairment of renal function. Otherwise, multiple indices with a large range of inter-patient values has not favoured a methodological and interpretative consensus. Furthermore, the poor specificity of renogram patterns does not allow for discrimination of all etiologies with only one scintigraphy. Nevertheless, follow-up with iterative scintigraphy may be helpful due to the high intra-patient reproducibility and to the early appreciate change of parameters, according to clinical and histological renal post-transplant outcome. (authors). 43 refs., 8 figs