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Sample records for renal tubular tumors

  1. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  2. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  3. Renal tubular acidosis.

    Science.gov (United States)

    Rothstein, M; Obialo, C; Hruska, K A

    1990-12-01

    Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment

  4. 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

    (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...... metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available...

  5. Renal tubular acidosis type 4 in pregnancy.

    Science.gov (United States)

    Jakes, Adam Daniel; Baynes, Kevin; Nelson-Piercy, Catherine

    2016-03-17

    We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained. 2016 BMJ Publishing Group Ltd.

  6. Genetics Home Reference: renal tubular dysgenesis

    Science.gov (United States)

    ... groups? Genetic Changes Mutations in the ACE , AGT , AGTR1 , or REN gene can cause renal tubular dysgenesis . ... receptor type 1 (AT1 receptor; produced from the AGTR1 gene), stimulating chemical signaling. By binding to the ...

  7. Screening renal stone formers for distal renal tubular acidosis

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...

  8. Renal histology and immunopathology in distal renal tubular acidosis.

    Science.gov (United States)

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  9. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    Science.gov (United States)

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  10. Distal renal tubular acidosis with hereditary spherocytosis.

    Science.gov (United States)

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  11. Mechanisms in hyperkalemic renal tubular acidosis.

    Science.gov (United States)

    Karet, Fiona E

    2009-02-01

    The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia.

  12. The syndrome of renal tubular acidosis with nerve deafness.

    Science.gov (United States)

    Donckerwolcke, R A; Van Biervliet, J P; Koorevaar, G; Kuijten, R H; Van Stekelenburg, G J

    1976-01-01

    Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.

  13. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    Science.gov (United States)

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim

    2017-09-12

    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Luminal nucleotides are tonic inhibitors of renal tubular transport

    DEFF Research Database (Denmark)

    Leipziger, Jens Georg

    2011-01-01

    PURPOSE OF REVIEW: Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. RECENT FINDINGS: Purinergic receptors are expressed...... in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal...... tubular absorption via P2 receptors. The apical P2Y2 receptor plays a crucial role in this process. ATP is released continuously into the tubular lumen. The release is augmented in response to an increase of tubular flow and after stimulation of G-protein-coupled receptors. The primary cilium appears...

  15. Inherited renal tubular defects with hypokalemia

    Directory of Open Access Journals (Sweden)

    Muthukrishnan J

    2009-01-01

    Full Text Available Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter′s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman′s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  16. 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...

  17. Renal primitive neuroectodermal tumors.

    Science.gov (United States)

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  18. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all...... the elements necessary for agonist-mediated intercellular communication. ATP is released from epithelial cells, which activates P2 receptors in the apical and basolateral membrane and thereby modulates tubular transport. Termination of the signal is conducted via the breakdown of ATP to adenosine. Recent far......-reaching advances indicate that ATP is often used as a local transmitter for classical sensory transduction. This transmission apparently also applies to sensory functions in the kidney. Locally released ATP is involved in sensing of renal tubular flow or in detecting the distal tubular load of NaCl at the macula...

  19. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all ...

  20. The rebirth of interest in renal tubular function.

    Science.gov (United States)

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate.

  1. Renal pathophysiologic role of cortical tubular inclusion bodies.

    Science.gov (United States)

    Radi, Zaher A; Stewart, Zachary S; Grzemski, Felicity A; Bobrowski, Walter F

    2013-01-01

    Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination.  This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.

  2. Klinefelter's syndrome with renal tubular acidosis: impact on height.

    Science.gov (United States)

    Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

    2010-02-01

    A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature.

  3. sup 99m Tc renal tubular function agents: Current status

    Energy Technology Data Exchange (ETDEWEB)

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references.

  4. Renal neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Brian R Lane

    2009-01-01

    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  5. Renal Tumor Biopsy Technique

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xue-Song Li; Li-Qun Zhou

    2016-01-01

    Objective:To review hot issues and future direction of renal tumor biopsy (RTB) technique.Data Sources:The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015.Study Selection:We included all the relevant articles on RTB technique in English,with no limitation of study design.Results:Computed tomography and ultrasound were usually used for guiding RTB with respective advantages.Core biopsy is more preferred over fine needle aspiration because of superior accuracy.A minimum of two good-quality cores for a single renal tumor is generally accepted.The use of coaxial guide is recommended.For biopsy location,sampling different regions including central and peripheral biopsies are recommended.Conclusion:In spite of some limitations,RTB technique is relatively mature to help optimize the treatment of renal tumors.

  6. The glomerulo-tubular junction: a target in renal diseases.

    Science.gov (United States)

    Lindop, G B M; Gibson, I W; Downie, T T; Vass, D; Cohen, E P

    2002-05-01

    Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.

  7. 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

  8. Distal renal tubular acidosis with multiorgan autoimmunity: A case report

    NARCIS (Netherlands)

    M.J. Van Den Wildenberg (Maria J.); E.J. Hoorn (Ewout); N. Mohebbi (Nilufar); C.A. Wagner (Carsten); A.J.J. Woittiez; P.A.M. de Vries; P. Laverman (Peter)

    2015-01-01

    textabstractA 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered au

  9. Renal tubular leakage complicating microcephalic osteodysplastic primordial dwarfism.

    Science.gov (United States)

    Eason, J; Hall, C M; Trounce, J Q

    1995-01-01

    We describe a male infant with phenotypic and radiological features of microcephalic osteodysplastic primordial dwarfism type I/III. He showed severe osteoporosis and biochemical derangement owing to renal tubular leakage, which has not previously been reported in this condition. He died aged 5 months. Images PMID:7783178

  10. Distal renal tubular acidosis without renal impairment after use of tenofovir: a case report

    OpenAIRE

    2016-01-01

    Background Tenofovir, one of antiretroviral medication to treat human immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had never been reported. Case presentation A 20-year-old man with HIV infection developed nausea and vomiting without diarrhea after starting antiretroviral therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine test showed positive urine anio...

  11. Recent advances in renal tubular calcium reabsorption.

    NARCIS (Netherlands)

    Mensenkamp, A.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2006-01-01

    PURPOSE OF REVIEW: Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption. RECENT FINDINGS: The thiazide diuretics are known for their hypocalciuric effect. Recently, it has been demonstr

  12. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

    Science.gov (United States)

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-02-27

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

  13. Renal tubular function in children with beta-thalassemia minor.

    Science.gov (United States)

    Kalman, Süleyman; Atay, A Avni; Sakallioglu, Onur; Ozgürtaş, Taner; Gök, Faysal; Kurt, Ismail; Kürekçi, A Emin; Ozcan, Okan; Gökçay, Erdal

    2005-10-01

    beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

  14. Changes at the glomerulo-tubular junction in renal transplants.

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    Lee, S J; Howie, A J

    1988-12-01

    We studied by microscopy 377 biopsies, nephrectomies, and necropsy kidneys from 123 human renal transplants. We discovered two common abnormalities of the renal corpuscle, both affecting the glomerulo-tubular junction. Adhesion of the tip of the glomerular tuft to the origin of the tubule, as reported in various non-transplant glomerulopathies, was seen in 197 specimens (52 per cent). This change was common in material showing acute or chronic vascular rejection and glomerulopathy, and was almost universal in transplants that had been in place for over 1 year. Another change at the glomerulo-tubular junction, not previously highlighted, consisted of an infiltrate of lymphocytes or neutrophil polymorphs into the epithelium at the tubular origin. This change was seen in 145 specimens (38 per cent) and was associated with cellular rejection and ascending infection. These changes are of importance because they show two responses of the kidney to injury that involve the glomerulo-tubular junction and thus suggest that this part of the kidney has some specific properties that have been largely neglected up to now.

  15. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    Directory of Open Access Journals (Sweden)

    C. Ripoli

    2012-08-01

    Full Text Available Introduction: distal renal tubular acidosis (dRTA presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA.

  16. Hypokalemic periodic paralysis and distal renal tubular acidosis associated with renal morphological changes.

    Science.gov (United States)

    Gupta, Ratan; Saurabh, Kumar; Sharma, Shobha; Gupta, Riyanka

    2013-03-01

    We report an unusual case of 5-yrs-old girl presenting with recurrent episodic weakness with documented hypokalemia, polyuria and failure to thrive. The child was finally diagnosed as having distal renal tubular acidosis. Imaging studies revealed associated hypoechoic spaces in renal medulla. Long term treatment with alkali and maintenance of normokalemia lead to regression of these morphological changes.

  17. Everything you need to know about distal renal tubular acidosis in autoimmune disease

    NARCIS (Netherlands)

    T. Both (Tim); R. Zietse (Bob); E.J. Hoorn (Ewout); P.M. van Hagen (Martin); V.A.S.H. Dalm (Virgil); J.A.M. van Laar (Jan); P.L.A. van Daele (Paul)

    2014-01-01

    textabstractRenal acid-base homeostasis is a complex process, effectuated by bicarbonate reabsorption and acid secretion. Impairment of urinary acidification is called renal tubular acidosis (RTA). Distal renal tubular acidosis (dRTA) is the most common form of the RTA syndromes. Multiple pathophysi

  18. Malignant renal tumors in children

    Directory of Open Access Journals (Sweden)

    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  19. Teratoid Wilms′ tumor - A rare renal tumor

    Directory of Open Access Journals (Sweden)

    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  20. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

    Directory of Open Access Journals (Sweden)

    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  1. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

    Directory of Open Access Journals (Sweden)

    P Ravi

    2013-01-01

    Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.

  2. Type 4 renal tubular acidosis in a kidney transplant recipient

    Directory of Open Access Journals (Sweden)

    Manjunath Kulkarni

    2016-02-01

    Full Text Available We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim – sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  3. Type 4 renal tubular acidosis in a kidney transplant recipient.

    Science.gov (United States)

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  4. Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

    Directory of Open Access Journals (Sweden)

    R A Misgar

    2017-01-01

    Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  5. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  6. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  7. Differentiation between renal allograft rejection and acute tubular necrosis by renal scan

    Energy Technology Data Exchange (ETDEWEB)

    Delmonico, F.L.; McKusick, K.A.; Cosimi, A.B.; Russell, P.S.

    1977-04-01

    The usefulness of the renal scan in diagnosing technical complications in the transplant patient is well established. However, the ability of the renal scan to differentiate between acute rejection and acute tubular necrosis has remained uncertain. We have evaluated the effectiveness of the /sup 99m/Tc DTPA computer-derived time-activity curve of renal cortical perfusion, as well as data obtained from scintillation camera images, in making such diagnoses. Fifteen patients with a clinical diagnosis of either acute rejection or acute tubular necrosis, or both, were studied retrospectively. Technetium scan diagnoses did not agree with the clinical assessment in nine of the patients. Thus selection of a course of treatment should not be based on data obtained from the scan alone.

  8. Primary renal primitive neuroectodermal tumor.

    Science.gov (United States)

    Goel, V; Talwar, V; Dodagoudar, C; Singh, S; Sharma, A; Patnaik, N

    2015-01-01

    Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  9. Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    He, Ping; Li, Detian; Zhang, Beiru

    2014-08-01

    Ureteral obstruction leads to renal injury and progresses to irreversible renal fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence concerning whether losartan (an angiotensin II type I receptor antagonist) mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis following unilateral ureteral obstruction (UUO) in animal models. The aim of this study was to investigate the effect and mechanism of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or losartan. The controls underwent sham surgery. The renal tissues were collected 3, 5, 7 and 14 days after surgery for measurement of various indicators of renal fibrosis. UUO increased the expression levels of α‑smooth muscle actin and collagen I, and the extent of renal tubular fibrosis and apoptosis in a time‑dependent manner. Losartan treatment partially attenuated these responses. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3) and altered the expression levels of two apoptosis‑related proteins (Bax and Bcl2). Losartan treatment also partially attenuated these responses. The results indicated that losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appeared to be mediated by partial blockage of STAT3 phosphorylation.

  10. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

    Directory of Open Access Journals (Sweden)

    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  11. Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H

    1987-01-01

    Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive...... capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments....

  12. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  13. Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana.

    Science.gov (United States)

    Chadwick, David R; Sarfo, Fred S; Kirk, Elaine S M; Owusu, Dorcas; Bedu-Addo, George; Parris, Victoria; Owusu, Ann Lorraine; Phillips, Richard

    2015-12-01

    HIV infection is associated with increased risk of renal dysfunction, including tubular dysfunction (TD) related to antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is becoming available for ART in sub-Saharan Africa, although data on its long-term safety there is limited. We aimed to study the prevalence of HIV-associated renal dysfunction in Ghana and explore associations between proteinuria or TD and potential risk factors, including TDF use. A single-centre cross-sectional observational study of patients taking ART was undertaken. Creatinine clearance (CrCl) was calculated and proteinuria detected with dipsticks. Spot urinary albumin and protein:creatinine ratios (uACR/uPCR) were measured and further evidence of TD (defined as having two or more characteristic features) sought. Logistic regression analysis identified factors associated with proteinuria or TD. In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl proteinuria and TD was 7 %, 37 % and 15 %. Factors associated with proteinuria were baseline CD4-count [aOR 0.86/100 cell increment (95 % CI, 0.74-0.99)] and TDF use [aOR 2.74 (95 % CI, 1.38-5.43)]. The only factor associated with TD was TDF use [aOR 3.43 (95 % CI, 1.10-10.69)]. In a subset with uPCR measurements, uPCRs were significantly higher in patients taking TDF than those on other drugs (10.8 vs. 5.7 mg/mmol, p proteinuria and TD are common and associated with TDF use in Ghana. Further longitudinal studies to determine whether proteinuria, TD or TDF use are linked to progressive decline in renal function or other adverse outcomes are needed in Africa.

  14. Ossifying renal tumor of infancy.

    Science.gov (United States)

    Schelling, Johannes; Schröder, Annette; Stein, Raimund; Rösch, Wolfgang H

    2007-06-01

    A renal ossifying tumor of infancy is a rare event with few cases having been published, and the etiology has not yet been established. We report on two new cases of this unusual neoplasm. A 2-year-old boy presented with intermittent painless gross hematuria. After several diagnostic procedures, an open pyelolithotomy was performed and the histological diagnosis of renal tumor of infancy was finally made. The history of the second case is very similar. An 8-week-old infant presented with gross hematuria. As in the first case, an open pyelolithotomy was performed and a tumor entirely covered with blood clots was found in the renal pelvis and completely removed. A histological diagnosis of renal ossifying tumor of infancy was made. Using the literature available, the histological criteria and biological behavior are discussed, together with the diagnostic and therapeutic algorithm for this tumor. In infants with gross hematuria and a calcified (non-)invasive mass in the pelvi-calceal system, renal ossifying tumor should be considered in the differential diagnosis. MRI or CT scan offers a good diagnostic guide.

  15. Tubular kidney injury molecule-1 (KIM-1) in human renal disease

    NARCIS (Netherlands)

    van Timmeren, M. M.; van den Heuvel, M. C.; Bailly, V.; Bakker, S. J. L.; van Goor, H.; Stegeman, C. A.

    2007-01-01

    KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with ur

  16. 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.

  17. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  18. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation.

    Directory of Open Access Journals (Sweden)

    Li-Li Wen

    Full Text Available Perfluorinated chemicals (PFCs are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs. In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1 by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation.

  19. Contemporary treatment of renal tumors

    DEFF Research Database (Denmark)

    Nisen, Harry; Järvinen, Petrus; Fovaeus, Magnus

    2017-01-01

    questions on renal tumor management and surgical education was designed and sent to 91 institutions performing renal tumor surgery in 2015. The response rate was 68% (62 hospitals), including 28 academic, 25 central and nine district hospitals. Hospital volume was defined as low (LVH: ...% thermoablations. For RN and PN, the percentages of open, laparoscopic and robotic approaches were 47%, 40%, 13% and 47%, 20%, 33%, respectively. The mean complication rate (Clavien–Dindo 3–5) was 4.9%, and 30 day mortality (TDM) was 0.5%. The median length of hospital stay was 4 days. Training with a simulator...

  20. Prevalence of renal tubular dysfunction in beta thalassemia minor in shiraz

    Directory of Open Access Journals (Sweden)

    Ali Moradi Nakhodcheri

    2012-02-01

    Full Text Available  Background & objective: β-Thalassemia minor is an asymptomatic hereditary disease. The first study on the relation of renal tubular dysfunction and β-thalassemia minor was performed in 2002 but those studies seem inadequate.The main goal of this study is through evaluation of renal tubular function in 100 patients with thalassemia minor. Materials & Methods: 100 patients with β- thalassemia which confirmed by hemoglobin electrophoresis and CBC as well as RBC indices were studied.14 out of 100 cases exit because of Urinary Tract Infection, diabetes mellitus or hypertension.Complete chemistry profile was performed on serum and urine of all reminder 86 patients (46 female and 40 male. Patients classified into two groups: β-thalassemia minor with anemia and without anemia. Another control group include 50 healthy individuals also considered.Then data analyzed by proper statistical methods. Results: 20 out of 86 reminder cases e.g. 24% showed at least one index of renal tubular dysfunction.58% of patients was been anemic and 42% non anemic. The most prominent tubular dysfunction was seen in a 29 years old lady with glucosuria and without anemia. conclusion: β-Thalassemia minor is common in Iran specially in Fars province. This study revealed significant renal tubular dysfunction in patient with β-thalassemia minor. So it is necessary to check out thalassemic patients for renal function tests periodically. Key words: β-thalassemia, minor,renal tubular dysfunction

  1. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

    Science.gov (United States)

    Chen, Jun-Feng; Wu, Qi-Shun; Xie, Yu-Xian; Si, Bo-Lin; Yang, Ping-Ping; Wang, Wen-Yan; Hua, Qin; He, Qing

    2017-10-01

    Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria. © FASEB.

  2. Pathology of the idiopathic renal tubular proteinuria evaluated by the renal scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takeshi; Saotome, Yumiko; Fuse, Tomoko [Tokyo Fussa Hospital (Japan)] [and others

    1998-03-01

    In 10 patients matching to the temporal standards of the idiopathic renal tubular proteinuria disease, renal scintigrams using {sup 99m}Tc-dimercaptosuccinic acid (DMSA) and {sup 99m}Tc-mercaptoacetyl-glycylglycylglycine (MAG3) were performed. All patients were boys with age of 11.9 years and the median concentration of {beta}{sub 2}-macroglobulin in urea was 69,150 {mu}g/l. In the DMSA scintigram, there was no abnormalities of accumulation in the morphology, but %uptake of DMSA in all patients decreased, and that ranges from 2.8 to 10.9% per kidney, equivalent to 1/3 to 1/5 of the normal healthy controls. On the other hand, in the MAG3 scintigram, the vessel and the functional phases seemed to be normal except one case, but the excretion phase was delayed except one case. This disease had the impairment in the active transport on the vessel cavity side of the distal renal tubular cells, and will show in future symptoms other than the low molecular weight proteinuria. It is important to observe carefully the development of symptoms. (K.H.)

  3. Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

    Science.gov (United States)

    Wichapoon, Benjamas; Punsawad, Chuchard; Viriyavejakul, Parnpen

    2017-01-01

    In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). In malarial AKI, the process of apoptosis occurs in ATN. © 2016 Asian Pacific Society of Nephrology.

  4. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress.

    Science.gov (United States)

    Grahammer, Florian; Haenisch, Nora; Steinhardt, Frederic; Sandner, Lukas; Sander, Lukas; Roerden, Malte; Arnold, Frederic; Cordts, Tomke; Wanner, Nicola; Reichardt, Wilfried; Kerjaschki, Dontscho; Ruegg, Markus A; Hall, Michael N; Moulin, Pierre; Busch, Hauke; Boerries, Melanie; Walz, Gerd; Artunc, Ferruh; Huber, Tobias B

    2014-07-08

    Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTORC1 inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells, and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in countercurrent multiplication and urine concentration. Although mTORC2 partially compensated for the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice and caused pronounced apoptosis, diminished proliferation rates, and delayed recovery. These findings identify mTORC1 as an important regulator of tubular energy metabolism and as a crucial component of ischemic stress responses.

  5. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

    Directory of Open Access Journals (Sweden)

    Prabahar Murugesan

    2008-01-01

    Full Text Available Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phos-phorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diag-nosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.

  6. Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells.

    Science.gov (United States)

    Crambert, Susanne; Sjöberg, Agneta; Eklöf, Ann-Christine; Ibarra, Fernando; Holtbäck, Ulla

    2010-07-01

    Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.

  7. Tubulointerstitial Nephritis Complicated by Fanconi Syndrome and Renal Tubular Acidosis Associated with three autoimmune diseases

    OpenAIRE

    Io, Kumiko; Obata, Yoko; Nishino, Tomoya; Hirose, Misaki; Yamashita, Hiroshi; Uramatsu, Tadashi; Ichikawa, Tatsuki; Hayashi, Tomayoshi; Kawakami, Atsushi; Taguchi, Takashi; Kohno, Shigeru

    2013-01-01

    A 45-year-old woman experiencing back pain showed signs of metabolic acidosis and electrolyte imbalances. The results of blood and urine tests indicated Fanconi syndrome and renal tubular acidosis. An x-ray showed vertebral fractures, which were thought to responsible for the back pain. In addition, the patient had proteinuria and renal dysfunction; therefore, renal biopsy was performed, and tubulointerstitial nephritis (TIN) was diagnosed. While investigating TIN, primary biliary cirrhosis a...

  8. In Situ lactate dehydrogenase activiy-a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    , apoptosis and inflammation. Lactate dehydrogenase (LDH) activity has previously been suggested as a renal tubular injury marker, but has a major limitation in the sense that it can only be measured in terminal kidneys. By the use of a hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI) approach...... to monitor metabolic changes, we here investigate LDH activity and renal metabolism after IRI. This procedure gives a novel non-invasive method for investigation renal tissue injury in concern with IRI....

  9. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Karunarathne Suneth

    2012-07-01

    Full Text Available Abstract Background Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. Case presentation A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. Conclusion The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

  10. Intragraft Tubular Vimentin and CD44 Expression Correlate With Long-Term Renal Allograft Function and Interstitial Fibrosis and Tubular Atrophy

    NARCIS (Netherlands)

    J. Kers; Y.C. Xu-Dubois; E. Rondeau; N. Claessen; M.M. Idu; J.J.T.H. Roelofs; F.J. Bemelman; R.J.M. ten Berge; S. Florquin

    2010-01-01

    Background. Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker),

  11. Overall renal and tubular function during infusion of amino acids in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...... tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma...

  12. Overall renal and tubular function during infusion of amino acids in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...... tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma...

  13. Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.

    Science.gov (United States)

    Ramkumar, Nirupama; Stuart, Deborah; Mironova, Elena; Bugay, Vladislav; Wang, Shuping; Abraham, Nikita; Ichihara, Atsuhiro; Stockand, James D; Kohan, Donald E

    2016-07-01

    The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 mo of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+) excretion and investigated the signaling mechanisms by which PRR regulates Na(+) balance. No detectable differences in BP were observed between control and PRR KO mice fed normal- or low-Na(+) diets. However, compared with controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+) balance with normal- and low-Na(+) intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+) retention following angiotensin II (ANG II) infusion. Furthermore, PRR KO mice had significantly lower epithelial Na(+) channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT1, ERK1/2, or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+) wasting and reduces the hypertensive response to ANG II.

  14. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure.

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    Richard A Zager

    Full Text Available Studies of experimental acute kidney injury (AKI are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine, suffer from the need for semi-quantitative grading (renal histology, or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content. Lactate dehydrogenase (LDH release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min or to nephrotoxic (glycerol; maleate AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia, served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, -0.89 between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death.

  15. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of

  16. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  17. Tumor Seeding With Renal Cell Carcinoma After Renal Biopsy

    OpenAIRE

    M.F.B. Andersen; Norus, T.P.

    2016-01-01

    Tumor seeding following biopsy of renal cell carcinoma is extremely rare with an incidence of 1:10.000. In this paper two cases with multiple recurrent RRC metastasis in the biopsy tract following biopsy of renal tumor is presented and the current literature is shortly discussed.

  18. 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 tubulo-interstitia

  19. Biotransformation, transport and toxicity studies in rat renal proximal tubular cells.

    NARCIS (Netherlands)

    Haenen, H.E.M.G.

    1996-01-01

    SummaryRenal proximal tubular (RPT) cells can be exposed apically to glomerulary filtrated and basolaterally to non-filtrated nephrotoxic compounds. To excrete these compounds via the urine, RPT cells are equipped with transport systems able to transport nephrotoxicants from the basolateral to the a

  20. Gender Difference of Cadmium-induced Renal Tubular Dysfunction for Inhabitants in Toyama,Japan

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective The aim of the present study was to compare the gender differencefor cadmium-induced renal tubular dysfunction between the male and female inhabitants. MethodsUrinary β2-microglobulin was measured in 299 male (94%) and 342 female (92%) inhabitants aged54 - 72 years,and the development of renal tubular dysfunction for 11 years was studied in the 62married couples from them. Results A significantly higher cumulative incidence was found in bothmen and women in cudmium-polluted area,showing 68. 4% in men and 64.8% in women compared to15.3 % in men and 5.9 % in women in the reference areas. Relative risk of renal tubular dysfunctionin females (11.0) was higher than males (4.5). The ratios of urinary β2-nicroglobulin and glucosewere higher in women than those in men in both the cadmium-polluted areas and the reference areas.Conclusion Although almost identical incidences were detected between men and wonen, the changesin excretion of β2-microglobulin and glucose was greater in women than those in men. These findings sug-gest that renal tubular dysfunction might be more progressive in women than that in men.

  1. Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration.

    Science.gov (United States)

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina; Birn, Henrik; Verroust, Pierre J; Nevéus, Tryggve; Sundelin, Birgitta; Hertz, Jens Michael; Holmström, Gerd; Ericson, Katharina; Christensen, Erik I; Nielsen, Rikke

    2013-03-01

    The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients. Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples. In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli. This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

  2. Palliative embolization of renal tumors

    Directory of Open Access Journals (Sweden)

    Jaganjac Suad

    2015-01-01

    Full Text Available Background/Aim. Palliative embolization of renal tumors is the method of choice in the treatment of advanced inoperable renal cell carcinoma in patients with hematuria and pain. Patients with small tumors in the remaining solitary kidney who refuse surgery are suitable for this type of therapy as well as patients with centrally located inoperable tumors. The prerequisite for successful capillary embolization is the closure of the main arte-rial trunk with metal spirals. Methods. In the period from 2000 to 2010 we conducted 42 palliative embolizations. The average age of the patients was 75 years, including 26 men and 16 women. In 8 of the patients the intervention was repeated and in one with severe AV shunts embolization was performed 4 times. Embolization was performed with alcohol, Ivalon 150-250 μm and with metal coils. Results. No serious complications were observed during and after the intervention. Fourteen patient were still alive then and among the deceased patients the average survival time was 13.5 ± 10.8 months with the range of 1 to 56 months. The minimal survival time was 1 month with a maxi-mum survival time of 56 months. Conclusion. Our results are consistent with data in the literature. Survival in patients without metastases was longer than in those with metastases, as con-firmed by the 14 of the patients from the study. An additional therapeutic safety in the treatment of small cancers is provided with a combination therapy of embolization and radiofrequency thermoablation.

  3. A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; YANG Lin; WANG Ke-qiang; XU Shi-xiong; DAI Pei-dong

    2009-01-01

    Objective:To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods:A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic response (MR), tubuloglomerular feedback (TGF) and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results:The results predict the dynamics of renal autoregulation on its blood pressure and flow,and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion:The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.

  4. Protection of Renal Tubular Cells by Antioxidants: Current Knowledge and New Trends

    Directory of Open Access Journals (Sweden)

    Azar Baradaran

    2015-01-01

    Full Text Available Acute renal damage mainly develops following toxic or ischemic insults and is defined as acute. These damages have largely been attributed to oxidative stress. Recently much attention has been directed toward decreased renal tubular cell regeneration during tubular cell injury. Antioxidants have recently been the focus of researchers and scientists for prevention and treatment of various oxidative stress-related conditions, including renal toxicities. Although free radicals are known to contribute in kidney injury and abundant researches, particularly laboratory trials, have shown the beneficial effects of antioxidants against these complications, long term clinical trials do not uniformly confirm this matter,especially for single antioxidant consumption such as vitamin C. The aim of this paper is to discuss the possible explanation of this matter.

  5. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

    Science.gov (United States)

    Yılmaz, Hakkı; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Yıldırım, İ

    2013-07-01

    We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia.

  6. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells.

    Science.gov (United States)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury.

  7. Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells.

    Directory of Open Access Journals (Sweden)

    Damien Maggiorani

    Full Text Available Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2 were subjected to FSS (0.5 Pa for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1, Par polarity complex (Pard6, adherens junctions (E-Cadherin, β-Catenin and the primary cilium (α-acetylated Tubulin were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and β-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E-cadherin and β-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium.

  8. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

    Directory of Open Access Journals (Sweden)

    Hao Jia Wu

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF and TNFα-stimulating gene (TSG-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

  9. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril....... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  10. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

    Science.gov (United States)

    Wu, Hao Jia; Yiu, Wai Han; Li, Rui Xi; Wong, Dickson W L; Leung, Joseph C K; Chan, Loretta Y Y; Zhang, Yuelin; Lian, Qizhou; Lin, Miao; Tse, Hung Fat; Lai, Kar Neng; Tang, Sydney C W

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

  11. Reduction of metformin renal tubular secretion by cimetidine in man.

    OpenAIRE

    Somogyi, A.; Stockley, C; Keal, J; Rolan, P; Bochner, F

    1987-01-01

    To determine whether cimetidine altered the renal handling of metformin, seven subjects took 0.25 g metformin daily with and without cimetidine 0.4 g twice daily. Blood and urine samples were collected and assayed for metformin, cimetidine and creatinine by h.p.l.c. Cimetidine significantly increased the area under the plasma metformin concentration-time curve by an average of 50% and reduced its renal clearance over 24 h by 27% (P less than 0.008). There was no alteration in the total urinar...

  12. Renal tubular acidosis type IV as a complication of lupus nephritis.

    Science.gov (United States)

    Sánchez-Marcos, C; Hoffman, V; Prieto-González, S; Hernández-Rodríguez, J; Espinosa, G

    2016-03-01

    Renal tubular acidosis (RTA) is a rare complication of renal involvement of systemic lupus erythematosus (SLE). We describe a 24-year-old male with type IV lupus nephropathy as a presenting manifestation of SLE. He presented with improvement of renal function following induction therapy with three pulses of methylprednisolone and 500 mg biweekly pulses of cyclophosphamide. However, a week after the first pulse of cyclophosphamide, the patient presented with a significant increase in legs edema and severe hyperkalemia. Type IV RTA associated with hyporeninemic hypoaldosteronism was suspected in the presence of metabolic acidosis with a normal anion gap, severe hyperkalemia without worsening renal function, and urinary pH of 5. RTA was confirmed with a transtubular potassium concentration gradient of 2 and low levels of plasma aldosterone, renin, angiotensin II, and cortisol. Intravenous bicarbonate, high-dose furosemide, and fludrocortisone were administered with normalization of potassium levels and renal function.

  13. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    DEFF Research Database (Denmark)

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...

  14. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  15. HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.

    Science.gov (United States)

    Ross, Michael J; Fan, Cheng; Ross, Michael D; Chu, Te-Huatearina; Shi, Yueyue; Kaufman, Lewis; Zhang, Weijia; Klotman, Mary E; Klotman, Paul E

    2006-05-01

    HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-1 infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.

  16. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

    Science.gov (United States)

    Morizane, Ryuji; Monkawa, Toshiaki; Fujii, Shizuka; Yamaguchi, Shintaro; Homma, Koichiro; Matsuzaki, Yumi; Okano, Hideyuki; Itoh, Hiroshi

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  17. Renal Differentiation of Mesenchymal Stem Cells Seeded on Nanofibrous Scaffolds Improved by Human Renal Tubular Cell Lines-Conditioned Medium.

    Science.gov (United States)

    Ardeshirylajimi, Abdolreza; Vakilian, Saeid; Salehi, Mohammad; Mossahebi-Mohammadi, Majid

    Kidney injuries and renal dysfunctions are one of the most important clinical problems, and tissue engineering could be a valuable method for solving it. The objective of this study was to investigate the synergistic effect of renal cell line-conditioned medium and Polycaprolactone (PCL) nanofibers on renal differentiation of human mesenchymal stem cells (MSCs). In the current study, after stem cells isolation and characterization, PCL nanofibrous scaffold was fabricated using electrospinning methods and characterized morphologically, mechanically, and for biocompatibility. The renal differentiation of seeded MSCs on the surface of PCL nanofibers with and without human renal tubular cell lines-conditioned medium was investigated by evaluation of eight important renal-related genes expression by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. Fabricated nanofibrous scaffolds were good in all characterized items. Almost highest expression of all genes was detected in stem cells seeded on PCL under conditioned media in comparison with the stem cells seeded on PCL, tissue culture polystyrene (TCPS) under renal induction medium, and TCPS under conditioned medium. According to the results, PCL nanofibers in contribution with conditioned medium can provide the optimal conditions for renal differentiation of MSCs and could be a promising candidate for renal tissue engineering application.

  18. An experimental renal acidification defect in patients with hereditary fructose intolerance. I. Its resemblance to renal tubular acidosis.

    Science.gov (United States)

    Morris, R C

    1968-06-01

    In three unrelated patients with hereditary fructose intolerance (HFI), but in none of five normal subjects, the experimental administration of fructose invariably induced a reversible dysfunction of the renal tubule with biochemical and physiological characteristics of renal tubular acidosis. During a state of ammonium chloride-induced acidosis, (a) urinary pH was greater than six and the rate of excretion of net acid (titratable acid plus ammonium minus bicarbonate) was inappropriately low, (b) the glomerular filtration rate remained unchanged or decreased modestly, and (c) urinary excretion of titratable acid increased briskly with diuresis of infused phosphate, although urinary pH changed little. The tubular dysfunction, which also includes impaired tubular reabsorption of alpha amino nitrogen and phosphate, persisted throughout administration of fructose and disappeared afterward. The tubular dysfunction was not causally dependent on hypoglucosemia, ammonium chloride-induced acidosis or osmotic diuresis. Rather, it appeared causally related to the fructose-induced metabolic abnormality of patients with HFI. The causal enzymatic defect, the virtual absence of fructose-1-phosphate aldolase, occurs in the kidney as well as in the liver of patients with HFI.

  19. Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure.

    Science.gov (United States)

    Ohnishi, Hiroyuki; Mizuno, Shinya; Nakamura, Toshikazu

    2008-02-01

    During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.

  20. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.

  1. Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

    DEFF Research Database (Denmark)

    Osther, P J; Bollerslev, Jens; Hansen, A B

    1993-01-01

    Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had......-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA....

  2. Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury

    Institute of Scientific and Technical Information of China (English)

    冯娟

    2013-01-01

    Objective To explore the mechanism of protecting cells from hypoxia/reoxygenation(H/R) injury by constructing specific small interference RNA(siRNA) to inhibit NALP3 expression in rat renal tubular epithelial

  3. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H

    1986-01-01

    The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and sign.......56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics......./min) and fractional lithium clearance (from 0.31 +/- 0.03 to 0.44 +/- 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 +/- 0.03 to 0...

  4. [Mixed epithelial and stromal tumor growing with polypoid pattern in the renal pelvis].

    Science.gov (United States)

    Yamasaki, Toshinari; Yagihashi, Yuusuke; Iwamura, Hiroshi; Shirahase, Toshiaki; Hashimura, Takayuki; Katsura, Yoshitaka

    2004-01-01

    A 68-year-old woman was found incidentally to have right hydronephrosis and a renal pelvic mass by abdominal ultrasonography. Radiographic examinations revealed a heterogeneous renal pelvic tumor, and right nephroureterectomy was performed. The tumor was well circumscribed yellow-whitish solid mass with scattered cysts. Histologically, the tumor was composed of both mesenchymal and epithelial components. The mesenchymal elements consisted of fibroblasts and smooth muscle cells, and the epithelial elements of cystic and tubular structures lined by cuboidal epithelium. Atypia and mitoses were not identified. The patient was free of recurrence 42 months postoperatively. Mixed epithelial and stromal tumor of the kidney is a recently recognized neoplasm that occurs almost exclusively in perimenopausal woman. Similar tumors have been reported previously under various names, including adult mesoblastic nephroma and cystic hamartoma of the renal pelvis. Histogenesis of the tumor is still controversial.

  5. Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

    OpenAIRE

    Kwon, So-Youn; Bae, Ok-Nam; Noh, Ji-Yoon; Kim, Keunyoung; Kang, Seojin; Shin, Young-Jun; Lim, Kyung-Min; Chung, Jin-Ho

    2014-01-01

    Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described. Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity. Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induc...

  6. [Sjögren syndrome associated with renal tubular acidosis type I].

    Science.gov (United States)

    Górriz, L; Molino, R; Arjona, D; Estripeaut, D

    2000-01-01

    Primary Sjögren's Syndrome complicated with a renal tubular acidosis type 1 and hypocalcemic paralysis, as the principal clinical manifestation, is uncommon. Although the initial manifestations of the nephropathy are not well understood, it is believed that the invasion of mononuclear cells and the high level of circulating antibodies, play an important role in the pathogenesis of the disease. We present a patient with hypocalcemic paralysis as an initial manifestation of a latent Sjögren's disease. The glandular biopsy was normal, suggesting a mayor participation of an immunological humoral factor in the renal lesion.

  7. Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

    Directory of Open Access Journals (Sweden)

    Nobuhiko Satoh

    2015-01-01

    Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

  8. Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2016-09-01

    Full Text Available Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN. Endoplasmic reticulum (ER stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p. twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.

  9. Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report

    Directory of Open Access Journals (Sweden)

    Rakesh N. Bahadure

    2012-01-01

    Full Text Available Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis. Distal renal tubular acidosis (type I RTA is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic, pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year.

  10. Dental aspect of distal tubular renal acidosis with genu valgum secondary to rickets: a case report.

    Science.gov (United States)

    Bahadure, Rakesh N; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

    2012-01-01

    Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year.

  11. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

  12. [Itai-itai disease: cadmium-induced renal tubular osteomalacia].

    Science.gov (United States)

    Aoshima, Keiko

    2012-01-01

    Cadmium (Cd) is one of the most toxic elements to which humans could be exposed at work or in the environment. The outbreak of itai-itai disease, which is the most severe stage of chronic Cd poisoning, occurred in the Cd-polluted Jinzu River basin in Toyama. In this area, the river was contaminated by slag from a mine upstream; as a consequence, the soil in rice paddies was polluted with heavy metals including Cd through irrigation water from around 1910 to the 1960s. The government of Toyama prefecture carried out an extensive survey on Cd concentration in rice and soil of the paddy fields and declared that the upper layer of a total of 1500 ha of paddy fields should be replaced by nonpolluted soil. Then, an intervention program of soil replacement in the polluted paddy fields was continually carried out from 1980 to 2011. As a result, Cd concentration in rice markedly decreased. The kidney is the organ critically affected after long-term exposure to Cd. Proximal tubular dysfunction (RTD) has been found among the inhabitants of the Jinzu River basin. The very recent report by the Environmental Agency in Japan in 2009 has disclosed that b2-microglobulinuria with RTD is still found at a high prevalence among the inhabitants of the Jinzu River basin of both sexes. Twenty patients with itai-itai disease (1 male and 19 females), who attended our hospital and received medical examination during 2000 to 2008, had applied for recognition as itai-itai disease patients to the government of Toyama prefecture. In this paper, the recent epidemiological and clinical features of itai-itai disease are discussed on the basis of a review of the cases of these 19 female patients.

  13. Endothelial protein C receptor in renal tubular epithelial cells and ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... placenta, heart, liver and lung endothelial cell. However, there ... The effects of some reagents (high glucose, tumor necrosis factor–α and interleukin-1β) were measured by .... functional domains, including N terminal signal peptide ..... endothelial cell protein C receptor (EPCR) 23bp insert in patients with.

  14. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

    Science.gov (United States)

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

    2011-01-01

    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  15. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats.

    Science.gov (United States)

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD.

  16. Relationship between rickets and incomplete distal renal tubular acidosis in children

    Directory of Open Access Journals (Sweden)

    Oduwole Abiola O

    2010-08-01

    Full Text Available Abstract Background In the Sub Saharan Africa Rickets has now been established to be due primarily to calcium deficiency and sometimes in combination with vitamin D deficiency. The main thrust of management is calcium supplementation with or without vitamin D. An observation was made that some children with nutritional rickets do not respond to this management modality. The recently reported high prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA in adults with osteoporosis as brought to fore the possibility of this being a possible cause of calcium wastage and therefore the poor response in these group of children with rickets. Aim To determine the prevalence of idRTA amongst a cohort of subjects with rickets To show a relationship between rickets and incomplete distal renal acidosis To determine the response of children with rickets and idRTA to addition of Shohl's solution to therapy Methodology Two separate cohorts of children with rickets performed the ammonium chloride loading test to detect those with incomplete renal tubular acidosis. Following identification for idRTA, Shohl's solution was added to therapy of calcium and vitamin D supplementation and their response compared to those without idRTA on calcium and vitamin D supplementation solely. Results 50 children with rickets aged from two to six years of age and composed of 29 females and 21males were investigated. Incomplete renal tubular acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical and radiological parameters than those who hadn't. Rate of response on those with idRTA treated with Shohl's solution was at par with those without idRTA. Conclusion Incomplete idRTA exist amongst children with rickets and should be looked out for in severe rickets and older children. Treatment of idRTA will lead to optimal response and healing of rickets.

  17. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  18. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Damianovich, Maya; Ziv, Ilan; Aloya, Tali; Grimberg, Hagit; Levin, Galit; Reshef, Ayelet; Bentolila, Alfonso; Cohen, Avi; Shirvan, Anat [NeuroSurvival Technologies (NST) Ltd., Petah Tikva (Israel); Heyman, Samuel N.; Shina, Ahuva [Mt.Scopus and the Hebrew University Medical School, Department of Medicine, Hadassah Hospital, Jerusalem (Israel); Rosen, Seymour [Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Pathology, Boston, MA (United States); Kidron, Dvora [Meir Hospital, Department of Pathology, Kfar-Saba (Israel)

    2006-03-15

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  19. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  20. Hypokalemic periodic paralysis due to proximal renal tubular acidosis in a case with membranoproliferative glomerulonephritis.

    Science.gov (United States)

    Santra, Gouranga; De, Dibyendu; Sinha, Pradip Kumar

    2011-11-01

    Proximal renal tubular acidosis (pRTA) is a rare disorder. Hypokalemia may be associated with it; occasionally leading to features like hypokalemic periodic paralysis. Though pRTA is a tubulointerstitial kidney disease, glomerulonephritis may occasionally lead to pRTA by tubular damage through leaking proteins, cytokines or by inflammatory infiltrates. In our reported case a 27 year old male had recurrent episodes of hypokalemic quadriparesis. Investigations revealed features of pRTA including hypokalemia and non-anion-gap hyperchloremic metabolic acidosis. His urine pH dropped to 5 with NH4Cl loading test. Kidney biopsy showed membranoproliferative glomerulonephritis with tubulointerstitial damage. Hypokalemic periodic paralysis and pRTA are uncommon associations of membranoproliferative glomerulonephritis.

  1. Role of Stat3 Signaling in Control of EMT of Tubular Epithelial Cells During Renal Fibrosis

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    Jingsong Liu

    2017-08-01

    Full Text Available Background/Aims: Transforming growth factor β 1 (TGFβ1 plays a critical role in the epithelial-to-mesenchymal transition (EMT of renal tubular epithelial cells (TECs during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. Methods: Expression of TGFβ1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFβ1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. Results: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFβ1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. Conclusion: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.

  2. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways.

    Science.gov (United States)

    Thongnuanjan, Penjai; Soodvilai, Sirima; Chatsudthipong, Varanuj; Soodvilai, Sunhapas

    2016-01-01

    Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment.

  3. Renal tubular dysfunction in pediatric patients with beta-thalassemia major

    Directory of Open Access Journals (Sweden)

    Ali Ahmadzadeh

    2011-01-01

    Full Text Available To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca, protein, uric acid (UA, creatinine (Cr, urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN, fasting blood sugar, serum creatinine (SCr, electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16 years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR. The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L and 3.2 IU/L in the control group (P 0.21 (P = 0.006. Nine (6.4% thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2. Sixty-nine (49.3% out of the 140 patients and 45 (65.2% of the patients having UNAG had uricosuria also (UUA/UCr > 0.26. Ten (7% patients had microscopic hematuria and 10 (7% patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

  4. Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune hypothyroidism: an uncommon association.

    Science.gov (United States)

    Agarwal, Amit; Kumar, Pradeep; Gupta, Nomeeta

    2015-11-01

    A 14-year-old female came with the history of sudden onset weakness; during work up, she was found to have hyperchloremic metabolic acidosis with normal anion gap and normal renal function suggesting the possibility of renal tubular acidosis (RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti-Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium levels were low and she was treated with intravenous potassium chloride. After she recovered from acute hypokalemic paralysis, she was started on oral potassium citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone and thyroxine supplements. Over the next 6 months, she has significant reduction in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric population and its association with renal tubular acidosis is even rarer, we suggest considering Sjogren syndrome as a differential diagnosis during the RTA work-up is worth trying.

  5. Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway.

    Science.gov (United States)

    Su, Jinzi; Zou, Wenbo; Cai, Wenqin; Chen, Xiuping; Wang, Fangbing; Li, Shuizhu; Ma, Wenwen; Cao, Yangming

    2014-01-15

    Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.

  6. Effects of "in vivo" administration of baclofen on rat renal tubular function.

    Science.gov (United States)

    Donato, Verónica; Pisani, Gerardo Bruno; Trumper, Laura; Monasterolo, Liliana Alicia

    2013-09-05

    The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01-1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone.

  7. Effect of methoxychlor on Ca(2+) movement and viability in MDCK renal tubular cells.

    Science.gov (United States)

    Cheng, He-Hsiung; Lu, Yi-Chau; Lu, Ti; Cheng, Jin-Shiung; Mar, Guang-Yuan; Fang, Yi-Chien; Chai, Kuo-Liang; Jan, Chung-Ren

    2012-10-01

    The effect of the insecticide methoxychlor on the physiology of renal tubular cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) in MDCK renal tubular cells using the Ca(2+) -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca(2+) ](i) in a concentration-dependent manner. The signal was reduced by 80% by removing extracellular Ca(2+) . Methoxychlor-induced Ca(2+) entry was not affected by nifedipine and SK&F96365 but was inhibited by econazole and protein kinase C modulators. In Ca(2+) -free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) partly inhibited methoxychlor-induced [Ca(2+) ](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+) ](i) rise. Inhibition of phospholipase C with U73122 nearly abolished methoxychlor-induced [Ca(2+) ](i) rise. At 5-15 μM, methoxychlor slightly increased cell viability, whereas at 20 μM, it decreased viability. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that 10 μM methoxychlor inhibited apoptosis, while 20 μM methoxychlor enhanced apoptosis. Methoxychlor (10 and 20 μM) increased the production of reactive oxygen species. Together, in renal tubular cells, methoxychlor induced [Ca(2+) ](i) rise by inducing phospholipase C-dependent Ca(2+) release from multiple stores and Ca(2+) entry via protein kinase C- and econazole-sensitive channels. Methoxychlor slightly enhanced or inhibited cell viability in a concentration-dependent, Ca(2+) -independent manner. Methoxychlor induced cell death that may involve apoptosis via mitochondrial pathways.

  8. Calcium oxalate monohydrate crystals internalized into renal tubular cells are degraded and dissolved by endolysosomes.

    Science.gov (United States)

    Chaiyarit, Sakdithep; Singhto, Nilubon; Thongboonkerd, Visith

    2016-02-25

    Interaction between calcium oxalate crystals and renal tubular cells has been recognized as one of the key mechanisms for kidney stone formation. While crystal adhesion and internalization have been extensively investigated, subsequent phenomena (i.e. crystal degradation and dissolution) remained poorly understood. To explore these mechanisms, we used fluorescein isothiocyanate (FITC)-labelled calcium oxalate monohydrate (COM) crystals (1000 μg/ml of crystals/culture medium) to confirm crystal internalization into MDCK (Type II) renal tubular cells after exposure to the crystals for 1 h and to trace the internalized crystals. Crystal size, intracellular and extracellular fluorescence levels were measured using a spectrofluorometer for up to 48 h after crystal internalization. Moreover, markers for early endosome (Rab5), late endosome (Rab7) and lysosome (LAMP-2) were examined by laser-scanning confocal microscopy. Fluorescence imaging and flow cytometry confirmed that FITC-labelled COM crystals were internalized into MDCK cells (14.83 ± 0.85%). The data also revealed a reduction of crystal size in a time-dependent manner. In concordance, intracellular and extracellular fluorescence levels were decreased and increased, respectively, indicating crystal degradation/dissolution inside the cells and the degraded products were eliminated extracellularly. Moreover, Rab5 and Rab7 were both up-regulated and were also associated with the up-regulated LAMP-2 to form large endolysosomes in the COM-treated cells at 16-h after crystal internalization. We demonstrate herein, for the first time, that COM crystals could be degraded/dissolved by endolysosomes inside renal tubular cells. These findings will be helpful to better understand the crystal fate and protective mechanism against kidney stone formation.

  9. Renal Primitive Neuroectodermal Tumor: A Case Report.

    Science.gov (United States)

    Yang, Cheng; Xu, Hanjiang; Zhou, Jun; Hao, Zongyao; Wang, Jianzhong; Lin, Changmin; Zhang, Li; Zhu, Xia; Liang, Chaozhao

    2015-12-01

    Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor and typically arises from bone or soft tissue in adolescents and young adults. Renal PNET is extraordinarily rare and exhibits highly aggressive biological behavior with poor prognosis.We present here a new case of renal PNET in a 31-year-old female. The patients were referred to our hospital because of left flank pain with nausea and vomiting for 1 week. A computed tomography scan revealed a 14.7 × 12.7 cm well-defined, unevenly mass lesion with both solid and cystic components and the tumor was not enhanced uniformly.A preoperative diagnosis of cystic renal cell carcinoma and urinary tract infection was made. The patient undergone anti-inflammatory therapy followed by a left radical nephrectomy. Taken with morphological pattern and immunohistochemical markers, a diagnosis of renal PNET was made. Two cycles of combined chemotherapy were executed. At the 14-month follow-up, no evidence of metastasis or recurrence was indicated.This case reminds clinicians that for adolescents and young adults with a suspicious renal mass, a diagnosis of renal PNET should be always considered. An initial surgery followed by radiotherapy and chemotherapy is suggested for the therapeutic management.

  10. 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.

  11. Effects of uric acid on mitochondrial oxidative damage and apoptosis in human renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    张涛

    2014-01-01

    Objective To observe the effects of uric acid(UA)on mitochondrial oxidative damage and apoptosis in renal tubular epithelial cells(HK-2),and investigate the possible mechanism.Methods HK-2 cells were exposed to UA(480μmol/L,720μmol/L)for different time(0 h,24 h,48 h)in vitro.The mitochondrial ROS production was detected by Mito SOX staining.The mitochondrial membrane potential was measured by JC-1 staining.The expressions of prohibitin and AIF were examined by Western blotting and immunofluorescence cytochemistry.

  12. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    Science.gov (United States)

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

  13. Renal Tubular Acidosis after Jejunoileal Bypass for Morbid Obesity: role of secondary hyperparathyroidism

    DEFF Research Database (Denmark)

    Andersen, NN; Ladefoged, NN

    1991-01-01

    The effect of calcium infusion was studied in patients with renal tubular acidosis (RTA) and secondary hyperparathyroidism. Both developed after jejunoileal bypass operation (JIB) for morbid obesity. In three of four cases the acidification defect was abolished, probably due to a decrease of serum...... parathyroid hormone. As we found RTA in 9% (95% confidence limits 2-21%) of our patients, screening for acidosis is recommended in obesity patients after malabsorptive operations. RTA can be verified through an ammonium loading test. Before deciding on re-establishing bowel continuity due to RTA, we suggest...

  14. Renal tubular acidosis presenting as respiratory paralysis: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Kalita J

    2010-01-01

    Full Text Available Respiratory paralysis due to renal tubular acidosis (RTA is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L and hyperchloremic (110 meq/l acidosis (pH 7.1. She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

  15. [Renal cholesteatoma: keratin accumulation tumor].

    Science.gov (United States)

    González Castillo, P; Mora, M J; Mañas, A; Extramiana, J; Manzarbeitia, F; Pérez, M J; Paniagua, P; Pamplona, M

    1992-01-01

    Presentation of 6 cases of renal cholesteatoma in 4 male and 2 female patients ranging between 30 and 67 years of age. The most consistent clinical data was a history of relapsing nephritic colic of long-evolution. The average time to diagnose was 19 years. In 50% cases an association to malignant neoplastic pathology was found. The clinical diagnosis was based on the urography and the histopathological examination of the material passed with the urine. Renal exeresis was performed in 5 cases. One was treated in a conservative fashion. Also the etiology causes, diagnostic procedure and other therapeutic possibilities were reviewed.

  16. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption.

    Science.gov (United States)

    Birn, H; Fyfe, J C; Jacobsen, C; Mounier, F; Verroust, P J; Orskov, H; Willnow, T E; Moestrup, S K; Christensen, E I

    2000-05-01

    Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

  17. Distal renal tubular acidosis and quadriparaesis in Sjögren′s syndrome: A cunning congregate

    Directory of Open Access Journals (Sweden)

    Arundhati G Diwan

    2014-01-01

    Full Text Available Sjögren′s syndrome (SS is a chronic autoimmune disease, chiefly affecting the exocrine glandular function of salivary glands and lacrimal glands. Rarely, it involves the kidneys, central and peripheral nervous system, muscloskeletal apparatus and lungs. We report a rare constellation of SS with distal renal tubular acidosis and quadriparaesis in a young female. History of quadriparaesis was acute, with rapid progression. Supplementary treatment for severe hypokalemia was instituted at the earliest, lest the patient develop respiratory muscle weakness. Concomitantly, metabolic acidosis with alkaline urine was suspected and subsequently investigated. Eventually, this was attributed to impaired renal acidification of urine in the distal tubules. History of dryness of eyes and mouth since 6 months justified salivary gland biopsy. The results yielded a lymphocytic infiltrative pathology strongly favoring SS. The patient benefited from prompt potassium replacement therapy and had complete resolution over the next week. Supportive treatment for predictable manifestations was continued along with potassium supplements.

  18. Hereditary tubular transport disorders: implications for renal handling of Ca2+ and Mg2+

    DEFF Research Database (Denmark)

    Dimke, Henrik; Hoenderop, Joost G; Bindels, René J;

    2010-01-01

    The kidney plays an important role in maintaining the systemic Ca2+ and Mg2+ balance. Thus the renal reabsorptive capacity of these cations can be amended to adapt to disturbances in plasma Ca2+ and Mg2+ concentrations. The reabsorption of Ca2+ and Mg2+ is driven by transport of other electrolytes......, sometimes through selective channels and often supported by hormonal stimuli. It is, therefore, not surprising that monogenic disorders affecting such renal processes may impose a shift in, or even completely blunt, the reabsorptive capacity of these divalent cations within the kidney. Accordingly, in Dent......'s disease, a disorder with defective proximal tubular transport, hypercalciuria is frequently observed. Dysfunctional thick ascending limb transport in Bartter's syndrome, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, and diseases associated with Ca2+-sensing receptor defects, markedly...

  19. Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

    Science.gov (United States)

    Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

    2012-01-01

    Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

  20. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

    Science.gov (United States)

    Riveiro-Barciela, M; Campos-Varela, I; Tovar, J L; Vargas, V; Simón-Talero, M; Ventura-Cots, M; Crespo, M; Bilbao, I; Castells, L

    2011-12-01

    Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

  1. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.

    Science.gov (United States)

    Hansen, J M; Løkkegaard, H; Høy, C E; Fogh-Andersen, N; Olsen, N V; Strandgaard, S

    1995-01-01

    Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

  2. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

    Science.gov (United States)

    Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

    2017-01-01

    Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

  3. Role of TNF-associated cytokines in renal tubular cell apoptosis induced by hyperoxaluria.

    Science.gov (United States)

    Horuz, Rahim; Göktaş, Cemal; Çetinel, Cihangir A; Akça, Oktay; Aydın, Hasan; Ekici, Işın D; Albayrak, Selami; Sarıca, Kemal

    2013-06-01

    Crystal-cell interaction has been reported as one of the most crucial steps in urinary stone formation. Hyperoxaluria-induced apoptotic changes in renal tubular epithelial cells is the end-stage of this interaction. We aimed to evaluate the possible pathways responsible in the induction of apoptosis within the involved cells by assessing the receptoral expression of three different pathways. 16 male Spraque-Dowley rats were divided into two groups: Group 1 (n:8) received only distilled water; Group 2 (n:8) received 0.75 % ethylene glycol (EG) in their daily water to induce hyperoxaluria for 2 weeks. After 24 h urine collection, all animals were euthenized and right kidneys were removed and fixed for immunohistochemical evaluation. Oxalate and creatinine levels (in 24 h-urine) and FAS, tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor-2 expressions (in tissue) have been assessed. In addition to TNF (p = 0.0007) expression; both FAS (p = 0.0129 ) and FASL (p = 0.032) expressions significantly increased in animals treated with EG. The expressions of TRAIL (p = 0.49) and TRAIL-R2 (p = 0.34) receptors did not change statistically after hyperoxaluria induction. Although a positive correlation with cytokine expression density and 24 h-urinary oxalate expression (mg oxalate/mg creatinine) has been assessed with TNF (p = 0.04, r = 0.82), FAS (p = 0.05, r = 0.80), FAS-L (p = 0.04, r = 0.82); no correlation could be demonstrated between TRAIL and TRAIL R2 expressions. Our results indicate that apoptosis induced by oxalate is possibly mediated via TNF and FAS pathways. However, TRAIL and TRAIL-R2 seemed to have no function in the cascade. Correlation with urinary oxalate levels did further strengthen the findings.

  4. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    Science.gov (United States)

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

  5. The Effect of Connective Tissue Growth Factor on Human Renal Tubular Epithelial Cell Transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    张春; 朱忠华; 邓安国

    2004-01-01

    To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of α-smooth muscle actin (α-SMA) were assessed by indirect immuno-fluorescence, and the percentage of α-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of α-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of α-SMA were markedly stronger than that in negative controls. The percentages of α-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9 %, 65.5 % vs 2.4 %, P<0.01) . α-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).

  6. Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs.

    Science.gov (United States)

    Brands, Michael W; Bell, Tracy D; Rodriquez, Nancy A; Polavarapu, Praveen; Panteleyev, Dmitriy

    2009-02-01

    This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg.kg(-1).min(-1) iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging approximately 20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs.

  7. Primary renal carcinoid tumor: A radiologic review

    Directory of Open Access Journals (Sweden)

    Leslie Lamb, MD, Msc, Bsc

    2014-01-01

    Full Text Available Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney.

  8. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

    DEFF Research Database (Denmark)

    Bruun, N E; Ibsen, H; Skøtt, P

    1988-01-01

    1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155...... reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment...

  9. Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Jian Fei; Ying Chen; Bing Zhao; Zhi-Tao Yang; Lu Wang; Hui-Qiu Sheng

    2016-01-01

    Background:The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases,but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown.The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).Methods:A Sprague-Dawley rat HS model was established in vivo in this study.The expression level and location of DC-SIGN were observed in kidneys.Also,the degree of histological damage,the concentrations of tumor necrosis factor-α and interleukin-6 in the renal tissues,and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group),with or without VitC treatment before resuscitation,were evaluated.Results:HS induced DC-SIGN expression in rat tubular epithelial cells.The proinflammatory cytokine concentration,histological damage scores,and functional injury of kidneys had increased.All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.Conclusions:The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN,and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly.The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

  10. Systemic lupus erythematosus associated with type 4 renal tubular acidosis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Young Larry

    2011-03-01

    Full Text Available Abstract Introduction Type 4 renal tubular acidosis is an uncommon clinical manifestation of systemic lupus erythematosus and has been reported to portend a poor prognosis. To the best of our knowledge, this is the first case report which highlights the successful management of a patient with systemic lupus erythematosus complicated by type 4 renal tubular acidosis who did not do poorly. Case presentation A 44-year-old Hispanic woman developed a non-anion gap hyperkalemic metabolic acidosis consistent with type 4 renal tubular acidosis while being treated in the hospital for recently diagnosed systemic lupus erythematosus with multi-organ involvement. She responded well to treatment with corticosteroids, hydroxychloroquine and mycophenolate mofetil. Normal renal function was achieved prior to discharge and remained normal at the patient's one-month follow-up examination. Conclusion This case increases awareness of an uncommon association between systemic lupus erythematosus and type 4 renal tubular acidosis and suggests a positive impact of early diagnosis and appropriate immunosuppressive treatment on the patient's outcome.

  11. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.

    Science.gov (United States)

    Nagai, Junya; Takano, Mikihisa

    2014-08-15

    Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways.

  12. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients

    DEFF Research Database (Denmark)

    Hansen, J M; Løkkegaard, H; Høy, Carl-Erik

    1995-01-01

    volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR...... and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium...

  13. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates...... of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by......, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where...

  14. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates...... of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by......, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where...

  15. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

    Science.gov (United States)

    Flynn, F. V.; Lapsley, M.; Sansom, P. A.; Cohen, S. L.

    1992-01-01

    AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive

  16. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Science.gov (United States)

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  17. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  18. Renal tubular dysgenesis with hypocalvaria and ileocecal valve agenesis: an autopsy report

    Directory of Open Access Journals (Sweden)

    Ariel Barreto Nogueira

    2012-12-01

    Full Text Available Renal tubular dysgenesis (RTD is a rare, lethal, autosomal recessive disorder characterized by non-differentiation of the renal proximal convoluted tubules, resulting in oligohydramnios. It is usually diagnosed in the second trimester of pregnancy, following the oligohydramnios sequence, pulmonary hypoplasia and hypocalvaria. The prognosis is poor, and death usually occurs in utero or within the first few days of life. The pathogenesis of RTD is associated with the perinatal use of drugs, such as angiotensin- converting enzyme inhibitors, angiotensin II receptor antagonists, and anti- inflammatory drugs, as well as with fetal transfusion syndrome, genetic mutations in the pathway of the renin-angiotensin system pathway, cocaine snorting, or other pathological mechanisms that reduce renal blood flow. Here, we report the autopsy of a neonate born to consanguineous parents at 38 weeks of gestation, with RTD, decreased amniotic fluid, oligohydramnios sequence, hypocalvaria, pulmonary hypoplasia, and ileocecal valve agenesis. To our knowledge, the latter has never been reported associated with RTD.

  19. Effect of hepatitis B virus X gene on apoptosis and immune molecules of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    王轩

    2013-01-01

    Objective To investigate the effect of hepatitis B virus X(HBX)gene on apoptosis and immune moleculesof human proximal renal tubular epithelial cell line(HK-2).Methods The eukaryotic vector pcDNA3.1-myc-HBX containing HBX gene was transiently transfected into

  20. Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.

    Directory of Open Access Journals (Sweden)

    Calpurnia Jayakumar

    Full Text Available BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.

  1. Renal tubular acidosis type II associated with vitamin D deficiency presenting as chronic weakness.

    Science.gov (United States)

    Ali, Yaseen; Parekh, Amila; Baig, Mirza; Ali, Taseen; Rafiq, Tazeen

    2014-08-01

    Chronic vitamin D deficiency, though common in the elderly, is often under diagnosed and when progressing to renal tubular acidosis type II (RTA 2) can cause several simultaneous electrolyte imbalances that may present with weakness and pain as chief symptoms. We present such a case that after months of evaluation and symptomatic treatment did not lead to an effective establishment of the etiology causing chronic weakness and body pain in an elderly female patient. Eventually, after a careful review of the patient's history, repeat physical examinations, laboratory data evaluation, and diagnostic testing led to the establishment of the diagnosis of proximal RTA 2 associated with vitamin D deficiency, which caused the patient to develop several remarkable secondary electrolyte imbalances such as hypokalemia, hypocalcemia, hypophosphatemia, acidemia, hyperparathyroidism, with weakness and body pain.

  2. Long-term follow-up in distal renal tubular acidosis with sensorineural deafness.

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    Peces, R

    2000-11-01

    A 20-year-old man presented with failure to thrive and bilateral genu valgum. On the basis of growth failure, skeletal deformity, hyperchloremic metabolic acidosis with alkaline urine and hypokalemia, nephrocalcinosis, and hearing loss, a diagnosis of distal renal tubular acidosis (DRTA) with sensorineural deafness was made. The genu valgum was treated by corrective osteotomy. Skeletal deformity was corrected and impaired growth improved after sustained therapy of metabolic acidosis with alkali supplementation. During an 8-year follow-up period the patient's glomerular filtration rate remained stable, the nephrocalcinosis did not progress, and his height increased 10 cm. Although nephrolithiasis led to atrophy of the right kidney, at last follow-up, when the patient was 44 years old, his creatinine clearance was 50 ml/min per 1.73 m2 body surface.

  3. [Urolithiasis due to renal tubular acidosis associated with Sjögren's syndrome].

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    Umekawa, T; Esa, A; Uemura, T; Kohri, K; Kurita, T; Ishikawa, Y; Iguchi, M; Kataoka, K

    1990-03-01

    We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) associated with Sjögren's syndrome. Laboratory results about RTA in 4 patients with Sjögrenhs syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome. The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis. When we examine patients with bilateral and multiple urolithiasis, particularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exist in the background.

  4. Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning.

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    Sakai, Norihiro; Hirose, Yasuo; Sato, Nobuhiro; Kondo, Daisuke; Shimada, Yuko; Hori, Yasushi

    2016-01-01

    A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis.

  5. Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus.

    Science.gov (United States)

    Im, Eun Joo; Lee, Jung Min; Kim, Ji Hyun; Chang, Sang Ah; Moon, Sung Dae; Ahn, Yu Bae; Son, Hyun Shik; Cha, Bong Yun; Lee, Kwang Woo; Son, Ho Young

    2010-01-01

    A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

  6. Transient distal renal tubular acidosis following hump nosed viper bite: Two cases from Sri Lanka

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    Ranga M Weerakkody

    2016-01-01

    Full Text Available Hump-nosed viper (Hypnale hypnale; HNV is one of the six major snake species in Sri Lanka that cause envenomation. Nephrotoxicity, coagulopathy, and neurotoxicity are wellrecognized features of its envenomation. Type 4 renal tubular acidosis (RTA4 has only once been described previously in this condition, and we report two further cases. Two patients aged 53 and 51 presented following HNV bites with acute kidney injury and microangiopathic hemolytic anemia. Both underwent multiple cycles of hemodialysis until the polyuric phase was reached. Despite polyuria, both patients developed resistant hyperkalemia that needed further hemodialysis. The urinary pH, arterial pH, delta ratio, and transtubular potassium gradient confirmed RTA4. HNV venom has been shown to damage the proximal convoluted tubules in animal studies, but not the distal convoluted tubule, and hence the mechanism of our observation in these two patients is unclear. Unexplained hyperkalemia in recovery phase of HNV bite should raise suspicions of RTA4.

  7. Sjogren's syndrome with distal renal tubular acidosis presenting as hypokalaemic paralysis.

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    Vaidya, Gaurang; Ganeshpure, Swapnil

    2012-10-19

    A young lady with a history of repeated episodes of generalised weakness and fatigue presented to our hospital with similar symptoms and was found to have severe hypokalaemia. She had been previously diagnosed as hypokalaemic periodic paralysis but during this presentation she had also started complaining of the classic sicca-complex of Sjogren's syndrome, which was not present previously. On subsequent investigations she was found to have normal anion-gap metabolic acidosis with positive urine anion gap consistent with the diagnosis of distal renal tubular acidosis (RTA). It was thus concluded that the distal RTA secondary to Sjogren's syndrome was the cause of severe hypokalaemia in our patient. By presenting this case we aim to not only highlight one of the rare presentations of Sjogren's syndrome but also the favourable response of our patient to potassium replacement alone.

  8. Mandibular brown tumor in renal osteodystrophy

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    Park, Jin Woo; Choi, Bo Ram; Huh, Kyung Hoe; Yi, Won Jin; Choi, Soon Chul [Department of Oral and Maxillofacial Radiology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Gang, In Tae [Department of Oral and Maxillofacial Surgery, Kangnam Sacred Heart Hospital, Hallym Medical Center, Seoul (Korea, Republic of)

    2008-12-15

    Brown tumor is a histologically benign lesion that is a serious complication of renal osteodystrophy because it may result in severe deformity and discomfort. We report a case of brown tumor, which occurred in a 35-year-old woman with chronic renal failure, who had been treated with hemodialysis for 14 years. The lesion was found on the lingual side of the mandible. Standard panoramic radiograph showed generally decreased bone mineral density, loss of lamina dura, and thin cortical plates. Computed tomography (CT) revealed multilocular expansible lesions with heterogeneous attenuation in the anterior mandible, as well as generalized trabecular alteration with homogeneous sclerosis, and thinning or obliteration of cortical plates. Excision of the mandibular lesion and curettage of the affected bone were performed.

  9. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    OpenAIRE

    Mujeeburahiman Thottathil; Ashish Verma; Nischith D′souza; Altaf Khan

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too.

  10. The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells.

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    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H

    2011-06-24

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis.

  11. The Small GTPase Cdc42 Is Necessary for Primary Ciliogenesis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H.

    2011-01-01

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. PMID:21543338

  12. Survey on relation between Major Thalassemia and Desferiexamine with renal tubular damage.

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    H.M. Jafari, M.D.

    2007-01-01

    Full Text Available AbstractBackground and Purpose: Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major (TM patients in comparison with control group.Materials and Methods: This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test (t, chi square.Results: the Total of 84 (42 patients and, 42 controls patients were studied. The Mean age of the patients was years. Dose of Deferral was 70±19 mg/kg. The results showed no significant statistical differences in levels of microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups.Conclusion: In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with sever anemia, high dose desferal and Iron over load.

  13. Competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by probenecid

    Science.gov (United States)

    Landersdorfer, Cornelia B; Kirkpatrick, Carl M J; Kinzig, Martina; Bulitta, Jürgen B; Holzgrabe, Ulrike; Jaehde, Ulrich; Reiter, Andreas; Naber, Kurt G; Rodamer, Michael; Sörgel, Fritz

    2010-01-01

    AIMS Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532–41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography–tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without probenecid were modelled simultaneously with WinNonlin®. RESULTS Data are ratio of geometric means (90% confidence intervals). Addition of probenecid reduced the median renal clearance from 23.8 to 8.25 l h−1[65% reduction (59, 71), P ciprofloxacin and from 20.5 to 8.26 l h−1 (66% reduction (57, 73), P ciprofloxacin nonrenal clearance by 8% (1, 14) (P ciprofloxacin and M1 by probenecid. The affinity for the renal transporter was 4.4 times higher for ciprofloxacin and 3.6 times higher for M1 than for probenecid, based on the molar ratio. Probenecid did not affect volume of distribution of ciprofloxacin or M1, nonrenal clearance or intercompartmental clearance of ciprofloxacin. CONCLUSIONS Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected. PMID:20233180

  14. Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells

    Institute of Scientific and Technical Information of China (English)

    Cun-Liang Deng; Xin-Wen Song; Hai-Jun Liang; Chen Feng; Yun-Jian Sheng; Ming-Yong Wang

    2006-01-01

    AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN).METHODS: The levels of serum TGF-β1 were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative(20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer.RESULTS: The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01±5.85% and 17.58±8.35%, HBV DNA negative serum group 8.12±2.80% and 6.96 ± 2.76% than those in control group 4.25±0.65% and 2.33 ± 1.09%, respectively (P < 0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P < 0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-β1 in CHB group was 163.05 ± 91.35 μg/L, significantly higher as compared with 81.40 ± 40.75 μg/L in the control group (P < 0.01).CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-β1 may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.

  15. Prohibitin is associated with antioxidative protection in hypoxia/reoxygenation-induced renal tubular epithelial cell injury

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    Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Huang, Wei-Fang; Drummen, Gregor P. C.

    2013-11-01

    Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735 each P < 0.01), but positively correlated with superoxide dismutase, glutathione and mitochondrial membrane potential (r = 0.807, 0.815, 0.739; each P < 0.01). We postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

  16. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

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    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  17. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

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    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  18. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice.

    Science.gov (United States)

    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  19. Renal cell carcinoma with areas mimicking renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Grossmann, Petr; Hora, Milan; Sperga, Maris; Montiel, Delia Perez; Martinek, Petr; Gutierrez, Maria Evelyn Cortes; Bulimbasic, Stela; Michal, Michal; Branzovsky, Jindrich; Hes, Ondrej

    2013-07-01

    We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for α-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for α-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.

  20. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells

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    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis. PMID:27936102

  1. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.

    Science.gov (United States)

    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito; Kihara, Akio

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.

  2. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

    Science.gov (United States)

    Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

    2013-02-01

    The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

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

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    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.

  4. Connexin 30 deficiency impairs renal tubular ATP release and pressure natriuresis.

    Science.gov (United States)

    Sipos, Arnold; Vargas, Sarah L; Toma, Ildikó; Hanner, Fiona; Willecke, Klaus; Peti-Peterdi, János

    2009-08-01

    In the renal tubule, ATP is an important regulator of salt and water reabsorption, but the mechanism of ATP release is unknown. Several connexin (Cx) isoforms form mechanosensitive, ATP-permeable hemichannels. We localized Cx30 to the nonjunctional apical membrane of cells in the distal nephron and tested whether Cx30 participates in physiologically important release of ATP. We dissected, partially split open, and microperfused cortical collecting ducts from wild-type and Cx30-deficient mice in vitro. We used PC12 cells as ATP biosensors by loading them with Fluo-4/Fura Red to measure cytosolic calcium and positioning them in direct contact with the apical surface of either intercalated or principal cells. ATP biosensor responses, triggered by increased tubular flow or by bath hypotonicity, were approximately three-fold greater when positioned next to intercalated cells than next to principal cells. In addition, these responses did not occur in preparations from Cx30-deficient mice or with purinergic receptor blockade. After inducing step increases in mean arterial pressure by ligating the distal aorta followed by the mesenteric and celiac arteries, urine output increased 4.2-fold in wild-type mice compared with 2.6-fold in Cx30-deficient mice, and urinary Na(+) excretion increased 5.2-fold in wild-type mice compared with 2.8-fold in Cx30-deficient mice. Furthermore, Cx30-deficient mice developed endothelial sodium channel-dependent, salt-sensitive elevations in mean arterial pressure. Taken together, we suggest that mechanosensitive Cx30 hemichannels have an integral role in pressure natriuresis by releasing ATP into the tubular fluid, which inhibits salt and water reabsorption.

  5. [Microsurgical resection of lumbar intraspinal tumors through paraspinal approach using percutaneous tubular retractor system].

    Science.gov (United States)

    Chunmei, Chen; Gangfeng, Cai; Rui, Wang; Weiqiang, Zhang; Yan, Chen; Feng, Li; Chunhua, Wang; Fan, Wang; Zhijie, Chen; Songsheng, Shi; Weizhong, Yang

    2015-04-07

    To evaluate the clinical outcomes and operative techniques of microsurgical resection of lumbar intraspinal tumors through paraspinal approach by percutaneous tubular retractor system. A retrospective study was conducted to analyze 21 patients with lumbar intraspinal tumors between November 2011 and February 2014, including Schwannoma (n = 19) and meningioma (n = 2) without lumbar instability on preoperative images. The length of tumors was 0.6-2.0 cm. Tracheal intubation anesthesia was performed prior to microsurgery using percutaneous tubular retractor system through paraspinal approach. Operative duration, blood loss volume, postoperative wound pain duration and hospital stay were analyzed. Creatine phosphokinase (CPK-MM) level was recorded at 1 day preoperatively, 1 day, 3 days and 5 days postoperatively. The scores of Japanese Orthopedic Association (JOA) and visual analog scale (VAS) were analyzed at 1 day preoperatively, 1, 3, 5 days and 6 months postoperatively to evaluate the function status of spinal cord. Computed tomography ( CT) three-dimensional reconstruction of lumbar vertebrae was performed at 1 week postoperatively. Magnetic resonance imaging ( MRI) plain scan and enhanced scan of lumbar vertebrae were conducted preoperatively, 1 week and 6 months postoperatively. Complete removal of tumors was achieved in all patients without the injuries of spinal cord or nerve root. Postoperative scores of JOA and VAS improved versus preoperative ones (P spinal instability was identified by CT three-dimensional reconstruction. And no spinal deformity occurred during a follow-up period of 6-28 months. Microsurgical resection of lumbar intraspinal tumors using percutaneous tubular retractor system through paraspinal approach minimizes the injuries of paraspinal muscles, facet joint, spinous process and ligaments. This technique offers the advantages of mini-invasiveness, shorter hospital stay, rapid recovery and preserved postoperative spinal stability.

  6. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  7. Sequenciamento total do exoma como ferramenta de diagnóstico de acidose tubular renal distal

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    Paula Cristina Barros Pereira

    2015-12-01

    Full Text Available Resumo Objetivo A acidose tubular renal distal (ATRd é caracterizada por acidose metabólica devido à excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd com uso do sequenciamento total do exoma. Métodos Selecionamos duas famílias não relacionadas, quatro crianças com ATRd e seus pais, para fazer o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve perda auditiva severa. Fizemos o sequenciamento total do exoma em dois conjuntos de amostras e confirmamos os achados com o método de sequenciamento de Sanger. Resultados Duas mutações foram identificadas nos genes ATP6V0A4 e ATP6V1B1. Na família um, detectamos uma nova mutação no éxon 13 do gene ATP6V0A4 com uma alteração em um nucleotídeo único GAC → TAC (c.1232G>T que causou substituição de ácido aspártico por tirosina na posição 411. Na família dois, detectamos uma mutação recorrente do homozigoto com inserção de um par de bases (c.1149_1155insC no éxon 12 do gene ATP6V1B1. Conclusão Nossos resultados confirmam o valor do sequenciamento total do exoma para o estudo de nefropatias genéticas complexas e permitem a identificação de mutações novas e recorrentes. Adicionalmente, demonstramos claramente pela primeira vez a aplicação desse método molecular em doenças tubulares renais.

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

    Science.gov (United States)

    Xiao, Yun; Liu, Jishi; Peng, Yu; Xiong, Xuan; Huang, Ling; Yang, Huixiang; Zhang, Jian; Tao, Lijian

    2016-01-01

    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.

  9. Renal tumor and trauma: a pitfall for conversative management

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    Simone de Campos Vieira Abib

    2011-08-01

    Full Text Available PURPOSE: Conservative management has been largely used for renal trauma. Although this approach is safe and highly recommended, it can hide a pre-existing unknown condition, such as tumors or urinary malformations. A high index of suspicion is needed for early recognition of these conditions. We present four cases treated at the Pediatric Oncology Institute - Federal University of São Paulo, which have been initially treated conservatively for renal trauma. MATERIALS AND METHODS: We reviewed all 218 renal cases of renal tumors treated at our institution in a 22-year period, searching for associated trauma events. RESULTS: Four cases of renal tumors were initially treated conservatively for blunt renal trauma of low energy mechanism. Patients' ages ranged from 7 to 12 years old. Two patients had no previous symptoms, one patient had hematuria and another had an abdominal mass. Computerized Axial Tomography (CT of the abdomen revealed disparate magnitude of the renal bleeding to the low energy mechanism of trauma. All patients underwent surgical treatment. Kidney specimens showed Wilms tumor in three cases and renal carcinoma in one. CONCLUSIONS: The association between renal tumors and trauma should be suspected when renal trauma hemorrhage on abdominal CT scan does not match the low energy mechanism of blunt abdominal trauma. The key for a successful diagnosis of renal tumor or congenital malformations is the high index of suspicion for these conditions.

  10. Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter;

    2010-01-01

    rHuEPO elevates hemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. 16 healthy males were given rHuEPO...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO...... decreased plasma levels of renin and aldosterone (N = 8) by 21 - 33 % (P EPO values returned to baseline. On days 11 and 29 C(Li) increased (P

  11. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  12. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats

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    Maneksh Delinda

    2010-01-01

    Full Text Available Background and Purpose : A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA and respiratory failure. The mechanism of toxicity is unclear. Objectives : To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s of action. Materials and Methods : Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. Results : The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation , acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K + did not increase in human blood incubated with C. collinus extract. Conclusions and Implications : Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

  13. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Ladefoged, S D; Feldt-Rasmussen, B;

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  14. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

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    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  15. Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy.

    Science.gov (United States)

    Dauchy, Frédéric-Antoine; Lawson-Ayayi, Sylvie; de La Faille, Renaud; Bonnet, Fabrice; Rigothier, Claire; Mehsen, Nadia; Miremont-Salamé, Ghada; Cazanave, Charles; Greib, Carine; Dabis, Francois; Dupon, Michel

    2011-08-01

    Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

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

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    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.

  17. Ceramide-Induced Apoptosis in Renal Tubular Cells: A Role of Mitochondria and Sphingosine-1-Phoshate

    Science.gov (United States)

    Ueda, Norishi

    2015-01-01

    Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus, the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria play a key role for ceramide-induced apoptosis by altered mitochondrial outer membrane permeability (MOMP). Ceramide enhances oligomerization of pro-apoptotic Bcl-2 family proteins, ceramide channel, and reduces anti-apoptotic Bcl-2 proteins in the MOM. This process alters MOMP, resulting in generation of reactive oxygen species (ROS), cytochrome C release into the cytosol, caspase activation, and apoptosis. Ceramide regulates apoptosis through mitogen-activated protein kinases (MAPKs)-dependent and -independent pathways. Conversely, MAPKs alter ceramide generation by regulating the enzymes involving ceramide metabolism, affecting ceramide-induced apoptosis. Crosstalk between Bcl-2 family proteins, ROS, and many signaling pathways regulates ceramide-induced apoptosis. Growth factors rescue ceramide-induced apoptosis by regulating the enzymes involving ceramide metabolism, S1P, and signaling pathways including MAPKs. This article reviews evidence supporting a role of ceramide for apoptosis and discusses a role of mitochondria, including MOMP, Bcl-2 family proteins, ROS, and signaling pathways, and crosstalk between these factors in the regulation of ceramide-induced apoptosis of RTCs. A balancing role between ceramide and S1P and the strategy for preventing ceramide-induced apoptosis by growth factors are also discussed. PMID:25751724

  18. Renal tubular injury induced by ischemia promotes the formation of calcium oxalate crystals in rats with hyperoxaluria.

    Science.gov (United States)

    Cao, Yanwei; Liu, Wanpeng; Hui, Limei; Zhao, Jianjun; Yang, Xuecheng; Wang, Yonghua; Niu, Haitao

    2016-10-01

    Hyperoxaluria and cell injury are key factors in urolithiasis. Oxalate metabolism may be altered by renal dysfunction and therefore, impact the deposition of calcium oxalate (CaOx) crystals. We investigated the relationship of renal function, oxalate metabolism and CaOx crystal deposition in renal ischemia. One hundred male Sprague-Dawley rats were randomly divided into four groups. Hyperoxaluria model (Group A and B) was established by feeding rats with 0.75 % ethylene glycol (EG). The left renal pedicle was clamped for 30 min to establish renal ischemia Groups (B and C), while Groups A and D underwent sham operation. Then, serum and urine oxalate (Ox), creatinine (Cr) and urea nitrogen (UN) levels were evaluated by liquid chromatography mass spectrometry (LCMS) and ion mass spectrum (IMS) at days 0, 2, 4, 7, and 14. CaOx crystallization was assessed by transmission electron microscope (TEM). A temporal and significant increase of serum Cr and UN levels was observed in Groups B and C compared to values obtained for Groups A and D (P renal tissue. Our results indicated that renal tubular injury induced by renal ischemia might not affect Ox levels but could promote CaOx crystal retention under hyperoxaluria.

  19. Benign phyllodes tumor with tubular adenoma-like epithelial component in FNAC: A diagnostic pitfall

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    Kishori M Panda

    2016-01-01

    Full Text Available Benign phyllodes tumor (BPT is a biphasic neoplasm composed of bland stromal and epithelial elements. Cytologic diagnostic criteria of BPT, though documented in the literature, diagnostic pitfalls in fine-needle aspiration cytology (FNAC may occur due to sampling error, high cellularity, ductal hyperplasia, paucity of stromal component, and occasional dissociation of epithelial cells. Here, we describe a case of BPT diagnosed by histology in a 19-year-old female, where FNAC features were inconclusive due to paucity of stromal component, predominance of tubular adenoma-like epithelial component, and due to the presence of other overlapping features with fibroadenoma.

  20. Benign phyllodes tumor with tubular adenoma-like epithelial component in FNAC: A diagnostic pitfall

    Science.gov (United States)

    Panda, Kishori M

    2016-01-01

    Benign phyllodes tumor (BPT) is a biphasic neoplasm composed of bland stromal and epithelial elements. Cytologic diagnostic criteria of BPT, though documented in the literature, diagnostic pitfalls in fine-needle aspiration cytology (FNAC) may occur due to sampling error, high cellularity, ductal hyperplasia, paucity of stromal component, and occasional dissociation of epithelial cells. Here, we describe a case of BPT diagnosed by histology in a 19-year-old female, where FNAC features were inconclusive due to paucity of stromal component, predominance of tubular adenoma-like epithelial component, and due to the presence of other overlapping features with fibroadenoma. PMID:28028339

  1. Utilidad de la recolección de orina de dos horas para el diagnóstico del tipo de acidosis tubular renal

    OpenAIRE

    Margarita Irene Rocha-Gómez; Samuel Zaltzman-Girshëvich; Silvestre García-de la Puente

    2015-01-01

    La acidosis tubular renal se caracteriza por acidosis metabólica hiperclorémica. El diagnóstico del tipo de acidosis tubular renal se realiza mediante la medición del transporte tubular máximo de bicarbonato y de la capacidad de acidificación urinaria; sin embargo, estas pruebas son invasivas y requieren determinaciones especializadas. Objetivo: comparar la utilidad de la recolección urinaria de dos horas, una prueba relativamente simple y al alcance de muchos laboratorios, con la medició...

  2. Immunoprofiles of Adult Renal Epithelial Tumors: Immunohistochemistry Is Still Essential for Diagnosis of Renal Tumors (A Comprehensive Update

    Directory of Open Access Journals (Sweden)

    Ayhan Ozcan

    2015-09-01

    Full Text Available Renal cell carcinoma (RCC is the third most common cancer of the genitourinary tract and accounts for approximately 2-3% of all cancer deaths. The recent classification of renal tumors, The International Society of Urological Pathology (ISUP Vancouver Classification of Renal Neoplasia, has been proposed new distinct epithelial tumors and provisional new entities. Although most renal tumors are morphologically diagnosed, they need to use a panel of immunomarkers due to their overlapping morphologic features in some cases such as benign mimickers and newly emerged tumor types. Overlapping morphologic features are especially complicated in small biopsies and in distinguishing metastatic RCCs from other tumors. Immunohistochemistry is still more useful in renal tumors than non-renal tumors. A wide panel has been performed in the differential diagnosis of renal tumors. If immunohistochemical results are conflict or unconvincing, a diagnosis of unclassified RCC is appropriate. For accurate diagnosis of RCC, it should be careful in performing immunohistochemistry on needle biopsy due to variable expressions of immunomarkers originated from heterogeneity in RCCs. Morphology is still gold standard, but immunohistochemistry should be kept in mind as a useful and supportive diagnostic tool upon morphological features of renal tumors as always. [J Interdiscipl Histopathol 2015; 3(3.000: 81-101

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

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    Huei-Fen Jheng

    2015-10-01

    Full Text Available 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.

  4. Hypercalcaemia of malignancy: evidence for a nonparathyroid humoral agent with an effect on renal tubular handling of calcium.

    Science.gov (United States)

    Ralston, S H; Fogelman, I; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1984-02-01

    The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

  5. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    Science.gov (United States)

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

  6. Cell-specific delivery of a transforming growth factor-beta type I receptor kinase inhibitor to proximal tubular cells for the treatment of renal fibrosis

    NARCIS (Netherlands)

    Prakash, Jai; de Borst, Martin H.; van Loenen - Weemaes, Annemiek M.; Lacombe, Marie; Opdam, Frank; van Goor, Harry; Meijer, Dirk K. F.; Moolenaar, Frits; Poelstra, Klaas; Kok, Robbert J.

    2008-01-01

    Purpose. Activation of tubular epithelial cells by transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally accumulating conjugate of a TGF-beta type-I receptor kinase inhibitor (TKI) and evaluated its

  7. Effect of felodipine on renal haemodynamics and tubular sodium handling after single-dose cyclosporin infusion in renal transplant recipients treated with azathioprine and prednisolone.

    Science.gov (United States)

    Madsen, J K; Kornerup, H J; Pedersen, E B

    1995-11-01

    A total of 25 renal transplant recipients, treated solely with prednisolone and azathioprine, were investigated in a randomized, double-blind, placebo-controlled, cross-over study. The effect of a single oral dose of felodipine 5 mg or placebo on: glomerular filtration rate (GFR); renal plasma flow (RPF); renal vascular resistance (RVR); renal tubular sodium and water handling, measured by the lithium clearance technique; plasma levels of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF) and arginine vasopressin (AVP); blood pressure (BP), and heart rate (HR) was studied before, during, and after an intravenous infusion of cyclosporin (CyA). Three consecutive clearance periods were performed, each lasting 1 h. During the second period, CyA (0.75 mg kg-1 body weight) was infused. Before infusion of CyA, felodipine caused a significant rise (6.7%) in RPF and lowered RVR, but did not change GFR significantly. The rise in RPF was abolished by infusion of CyA. After infusion, both GFR (7.8%) and RPF (9.4%) were significantly higher and RVR lower after felodipine than after placebo. Proximal tubular output and total sodium excretion were higher on the felodipine day before and after, but not during CyA infusion. In all three periods felodipine reduced both systolic and diastolic BP. In conclusion, a single dose of felodipine increases RPF and decreases blood pressure in renal transplant recipients not treated with CyA. Although some of these changes are abolished by an acute intravenous infusion of CyA, the effects of felodipine are present again also during the 1st hour after the infusion and thereby indicate at least in part some renal protective effect of felodipine. It is suggested that a higher dose of felodipine might also have been preventive against CyA renal side-effects during the acute infusion.

  8. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

    Directory of Open Access Journals (Sweden)

    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  9. Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Stefanović Nikola Z.

    2015-10-01

    Full Text Available Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP 3A5 (6986A>G and ABCB1 (3435C>T polymorphisms on tacrolimus (TAC dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.

  10. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Ingrid Stroo

    Full Text Available Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2, the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  11. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Science.gov (United States)

    Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J D; Butter, Loes M; Florquin, Sandrine; Leemans, Jaklien C

    2015-01-01

    Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R) injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2), the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  12. 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.

  13. Carcinoid tumor with bilateral renal involvement in a child.

    Science.gov (United States)

    Warrier, Raj P; Varma, Aditi Vian; Chauhan, Aman; Ward, Ken; Craver, Randal

    2011-12-01

    Carcinoid tumors are uncommon in children. Kidneys are rarely involved as they do not possess neuro-endocrine cells. Work up of painless hematuria after abdominal trauma in a 10-year-old boy revealed primary carcinoid tumors with metastasis to both kidneys. We were unable to find any previous reports of renal involvement by carcinoid tumor in children.

  14. Long-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation.

    Science.gov (United States)

    Hsu, Yung-Ho; Cheng, Chung-Yi; Chen, Yen-Cheng; Chen, Tso-Hsiao; Sue, Yuh-Mou; Tsai, Wei-Lun; Chen, Cheng-Hsien

    2012-08-15

    Adipokine leptin reportedly acts on the kidney in pathophysiological states. However, the influence of leptin on renal tubular epithelial cells is still unclear. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. This study aims to investigate the influence of long-term leptin treatment on gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) and mice. We monitored apoptosis and molecular mechanisms using annexin V/ propidium iodide staining and small interfering RNA transfection. In NRK-52E cells, leptin reduced gentamicin-induced apoptosis at 24h, but significantly increased apoptosis at 48 h. Long-term treatment of leptin decreased Bcl-x(L) expression and increased caspase activity in gentamicin-treated NRK-52E cells. Leptin also increased the expression of cyclooxygenase-2 (COX-2) and its product, prostaglandin E(2) (PGE(2)), in a dose-dependent manner. The COX-2 inhibitor, NS398 (N-[2-(Cyclohexyloxy)-4- nitrophenyl]methanesulfonamide), blocked PGE(2) augmentation and the pro-apoptotic effects of leptin. The addition of PGE(2) recovered the pro-apoptotic effect of leptin in NS398-treated NRK-52E cells. In a mouse animal model, a 10 day leptin treatment significantly increased gentamicin-induced apoptotic cells in proximal tubules. NS398 treatment inhibited this in vivo pro-apoptotic effect of leptin. Results reveal that long-term elevation of leptin induces COX-2-mediated PGE(2) augmentation in renal tubular cells, and then increases these cells' susceptibility to gentamicin-induced apoptosis.

  15. Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney

    DEFF Research Database (Denmark)

    Abildgaard, U; Amtorp, O; Holstein-Rathlou, N H;

    1988-01-01

    unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 micrograms kg-1 min-1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue...

  16. Insufici??ncia renal aguda em pacientes com doen??a glomerular: aspectos histol??gicos e papel da necrose tubular aguda

    OpenAIRE

    Tavares, Maria Brand??o

    2011-01-01

    A insufici??ncia renal aguda ?? comum em pacientes com s??ndrome nefr??tica, podendo requerer terapia de substitui????o renal e ser irrevers??vel. A insufici??ncia renal aguda nesses pacientes pode ser precipitada por processos infecciosos, hipovolemia, drogas nefrot??xicas; entretanto na maioria dos casos a etiologia n??o ?? identificada e a insufici??ncia renal aguda ?? considerada idiop??tica. A necrose tubular aguda foi associada ?? insufici??ncia renal aguda em adultos com les??o m??nima...

  17. Primary renal primitive neuroectodermal tumor: A rare presentation

    Directory of Open Access Journals (Sweden)

    V Goel

    2015-01-01

    Full Text Available Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of primary renal PNET have been reported to date. Most literature about rPNET is isolated case reports. We report a case of rPNET in a 39-year-old male with a pre-operative diagnosis of renal cell carcinoma with renal vein thrombosis. The patient underwent radical nephrectomy with thrombolectomy, and histopathological examination revealed a highly aggressive tumor composed of monotonous sheets of round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this tumor, prompt diagnosis and imparting effective chemotherapy regimen to the patient is required, and it is important to differentiate PNET from other small round-cell tumors because of different therapeutic approach.

  18. Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells.

    Science.gov (United States)

    Castellano, Giuseppe; Cafiero, Cesira; Divella, Chiara; Sallustio, Fabio; Gigante, Margherita; Pontrelli, Paola; De Palma, Giuseppe; Rossini, Michele; Grandaliano, Giuseppe; Gesualdo, Loreto

    2015-03-22

    Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the gene expression profile of renal tubular epithelial cells, stimulated with interferon-alpha. We validated microarray results through real-time polymerase chain reaction, flow cytometry on renal tubular epithelial cells, and through immunohistochemical analysis and confocal microscopy on renal biopsies. Type I interferons signature was characterized by MXA-specific staining in renal tubular epithelial cells; in addition, in situ hybridization showed that renal tubular epithelial cells were the major producers of interferon-alpha, indicating a potential autocrine effect. Whole-genome expression profile showed interferon-alpha induced up-regulation of genes involved in innate immunity, protein ubiquitination and switching to immunoproteasome. In accordance with the in vitro data, class IV lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. Our data indicate that type I interferons might have a pathogenic role in lupus nephritis characterized by an autocrine effect of interferon-alpha on renal tubular epithelial cells. Therefore we hypothesize that inhibition of type I interferons might represent a therapeutic target to prevent tubulo-interstitial damage in patients with lupus nephritis.

  19. Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor.

    OpenAIRE

    Phillips, A.O.; Steadman, R.; Topley, N; Williams, J. D.

    1995-01-01

    Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in...

  20. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hamidreza Haghighatkhah

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

  1. Gonadal vein tumor thrombosis due to renal cell carcinoma.

    Science.gov (United States)

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei

    2015-01-01

    Renal cell carcinoma (RCC) had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC.

  2. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B;

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  3. Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor-beta receptors.

    Science.gov (United States)

    Chiang, Tai-An; Yang, Yu-Lin; Yang, Ya-Ying; Hu, Min-Hsiu; Wu, Pei-Fen; Liu, Shu-Fen; Huang, Ruay-Ming; Liao, Tung-Nan; Hung, Chien-Ya; Hung, Tsung-Jen; Lee, Tao-Chen

    2010-03-01

    Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor-beta receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)-beta1, as mannitol (27.5 mM) significantly enhanced the TGF-beta1-induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF-beta RII at 336 residues in a time (0-24 h) and dose (5.5-38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF-beta RI in a dose- and time-course dependent manner. These observations may be closely related to decreased catabolism of TGF-beta RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF-beta RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half-life and inhibited the protein level of TGF-beta RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF-beta receptors by retarding proteasomal degradation of TGF-beta RI. This study clarifies the mechanism underlying hyperosmotic-induced renal fibrosis in renal distal tubule cells. (c) 2010 Wiley-Liss, Inc.

  4. Comparison of Ultrasound Corticomedullary Strain with Doppler Parameters in Assessment of Renal Allograft Interstitial Fibrosis/Tubular Atrophy.

    Science.gov (United States)

    Gao, Jing; Rubin, Jonathan M; Weitzel, William; Lee, Jun; Dadhania, Darshana; Kapur, Sandip; Min, Robert

    2015-10-01

    To compare the capability of ultrasound strain and Doppler parameters in the assessment of renal allograft interstitial fibrosis/tubular atrophy (IF/TA), we prospectively measured ultrasound corticomedullary strain (strain) and intra-renal artery Doppler end-diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI) in 45 renal transplant recipients before their kidney biopsies. We used 2-D speckle tracking to estimate strain, the deformation ratio of renal cortex to medulla produced by external compression using the ultrasound transducer. We also measured Doppler EDV, PSV and RI at the renal allograft inter-lobar artery. Using the Banff scoring system for renal allograft IF/TA, 45 patients were divided into the following groups: group 1 with ≤5% (n = 12) cortical IF/TA; group 2 with 6%-25% (n = 12); group 3 with 26%-50% (n = 11); and group 4 with >50% (n = 10). We performed receiver operating characteristic curve analysis to test the accuracy of these ultrasound parameters and duration of transplantation in determining >26% cortical IF/TA. In our results, strain was statistically significant in all paired groups (all p 26%, including 26%-50% and >50%) and low-grade (≤25%, including 0.05). The areas under the receiver operating characteristic curve for strain, EDV, PSV, RI and duration of transplantation in determining >26% cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively. Our results suggest that corticomedullary strain seems to be superior to Doppler parameters and duration of transplantation in assessment of renal allograft cortical IF/TA.

  5. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Affect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien;

    status: 1.2 (95%CI 1.0;1.3). Mean tumor size: 27 mm (95%CI 26;29). Mean follow-up time: 24 months (95%CI 20;27). A total of 16 patients (13%) were previously diagnosed with renal cancer and the majority of these patients had previously undergone nephrectomy. PADUA-score was found to be low or moderate......Background: Renal cryoablation is a valid treatment option for localized pT1a renal tumors and has been the modality of choice at Aarhus University Hospital since 2005. Anatomical tumor classification systems such as PADUA and RENAL scores were initially introduced as tools to evaluate complication...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between...

  6. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Effect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien;

    status: 1.2 (95%CI 1.0;1.3). Mean tumor size: 27 mm (95%CI 26;29). Mean follow-up time: 24 months (95%CI 20;27). A total of 16 patients (13%) were previously diagnosed with renal cancer and the majority of these patients had previously undergone nephrectomy. PADUA-score was found to be low or moderate......Background: Renal cryoablation is a valid treatment option for localized pT1a renal tumors and has been the modality of choice at Aarhus University Hospital since 2005. Anatomical tumor classification systems such as PADUA and RENAL scores were initially introduced as tools to evaluate complication...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between...

  7. Cell-specific delivery of a transforming growth factor-beta type I receptor kinase inhibitor to proximal tubular cells for the treatment of renal fibrosis.

    Science.gov (United States)

    Prakash, Jai; de Borst, Martin H; van Loenen-Weemaes, Annemiek M; Lacombe, Marie; Opdam, Frank; van Goor, Harry; Meijer, Dirk K F; Moolenaar, Frits; Poelstra, Klaas; Kok, Robbert J

    2008-10-01

    Activation of tubular epithelial cells by transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally accumulating conjugate of a TGF-beta type-I receptor kinase inhibitor (TKI) and evaluated its efficacy in vitro and in vivo. TKI was conjugated to the protein Lysozyme (LZM) via a platinum-based linker. TKI-LZM was evaluated in human tubular cells (HK-2) for its anti-fibrotic activity. Plasma, kidney and urine drug levels after a single intravenous dose of TKI-LZM in rats were determined by HPLC or immunodetection. Anti-fibrotic effects of TKI-LZM were examined in the unilateral ureteral obstruction (UUO) model. TKI-LZM conjugate was successfully synthesized at an 1:1 drug/carrier ratio, and inhibited TGF-beta1-induced procollagen-1alpha1 gene expression in HK-2 cells. In vivo, TKI-LZM accumulated rapidly in tubular cells and provided a local depot for 3 days. Interestingly, a single dose of TKI-LZM inhibited the activation of tubular cells and fibroblasts in UUO rats and reduced renal inflammation. In contrast, free TKI at an equimolar (low) dosage exhibited little effects. Inhibition of TGF-beta signaling by local drug delivery is a promising antifibrotic strategy, and demonstrated the important role of tubular activation in renal fibrosis.

  8. Disparate effects of roscovitine on renal tubular epithelial cell apoptosis and senescence: implications for autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Park, Jin-Young; Park, See-Hyoung; Weiss, Robert H

    2009-01-01

    Control of apoptosis in autosomal dominant polycystic kidney disease (ADPKD) and in at least some cancers is likely regulated by the endogenous cyclin kinase inhibitor p21, levels of this protein being decreased in ADPKD and increased in many malignancies. The cyclin kinase inhibitor roscovitine has shown efficacy in treatment of murine PKD. We asked how a single agent can be efficacious in both PKD and cancer. Renal tubular epithelial cells were incubated at diverse roscovitine concentrations; apoptosis and senescence were measured. Subsequently, levels of pro- and antiapoptotic proteins were evaluated. Renal tubular epithelial cells exposed to 'low' concentrations of roscovitine showed minimal apoptosis in association with markedly increased levels of the antiapoptotic protein p21, and these cells became senescent. Conversely, cells exposed to 'high' levels of roscovitine became apoptotic. The mechanism of antiapoptosis and senescence with 'low'-dose roscovitine involves augmentation of the antiapoptotic proteins. Data in this study provide a mechanistic explanation of how roscovitine is effective in PKD, and suggest that further study of this agent should focus on assessment of dose response. Furthermore, our discovery of senescence induced by a PKD effective drug suggests a new area of therapeutic investigation in this disease. (c) 2008 S. Karger AG, Basel.

  9. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

    Science.gov (United States)

    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy.

  10. Alpha-enolase on apical surface of renal tubular epithelial cells serves as a calcium oxalate crystal receptor

    Science.gov (United States)

    Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2016-10-01

    To search for a strategy to prevent kidney stone formation/recurrence, this study addressed the role of α-enolase on apical membrane of renal tubular cells in mediating calcium oxalate monohydrate (COM) crystal adhesion. Its presence on apical membrane and in COM crystal-bound fraction was confirmed by Western blotting and immunofluorescence staining. Pretreating MDCK cells with anti-α-enolase antibody, not isotype-controlled IgG, dramatically reduced cell-crystal adhesion. Immunofluorescence staining also confirmed the direct binding of purified α-enolase to COM crystals at {121} > {100} > {010} crystal faces. Coating COM crystals with urinary proteins diminished the crystal binding capacity to cells and purified α-enolase. Moreover, α-enolase selectively bound to COM, not other crystals. Chemico-protein interactions analysis revealed that α-enolase interacted directly with Ca2+ and Mg2+. Incubating the cells with Mg2+ prior to cell-crystal adhesion assay significantly reduced crystal binding on the cell surface, whereas preincubation with EDTA, a divalent cation chelator, completely abolished Mg2+ effect, indicating that COM and Mg2+ competitively bind to α-enolase. Taken together, we successfully confirmed the role of α-enolase as a COM crystal receptor to mediate COM crystal adhesion at apical membrane of renal tubular cells. It may also serve as a target for stone prevention by blocking cell-crystal adhesion and stone nidus formation.

  11. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  12. TWEAK Activates the Non-Canonical NFκB Pathway in Murine Renal Tubular Cells: Modulation of CCL21

    Science.gov (United States)

    Sanz, Ana B.; Sanchez-Niño, Maria D.; Izquierdo, Maria C.; Jakubowski, Aniela; Justo, Pilar; Blanco-Colio, Luis M.; Ruiz-Ortega, Marta; Selgas, Rafael; Egido, Jesús; Ortiz, Alberto

    2010-01-01

    TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFκB activation suggestive of engagement of the non-canonical NFκB pathway. We now explore TWEAK-induced activation of NFκB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFα activated different DNA-binding NFκB complexes. TWEAK-induced sustained NFκB activation was associated with NFκB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFα used as control), induced a delayed increase in CCL21a mRNA (3.5±1.22-fold over control) and CCL21 protein (2.5±0.8-fold over control), which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFκB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFα. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h). In vivo, TWEAK induced nuclear NFκB2 and RelB translocation and CCL21a mRNA (1.5±0.3-fold over control) and CCL21 protein (1.6±0.5-fold over control) expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2±0.9 vs 1.3±0.6-fold over healthy control) or deficiency of TWEAK (2±0.9 vs 0.8±0.6-fold over healthy control). Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1±1.4 vs 1.8±1-fold over healthy control). Our results thus identify TWEAK as a regulator of non-canonical NFκB activation and CCL21 expression in tubular cells thus promoting

  13. Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

    2013-11-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

  14. Influence of urinary sodium excretion on the clinical assessment of renal tubular calcium reabsorption in hypercalcaemic man.

    Science.gov (United States)

    Ralston, S H; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1986-06-01

    The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.

  15. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Wetzels, J.F.M.; Joles, J.A.; Christensen, E.I.; Verroust, P.J.; Li, D.; Oliver, N.; Xu, L.; Kok, R.J.; Goldschmeding, R.

    2010-01-01

    Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal ex

  16. Renal tubular epithelial-mesenchymal transition in kidney fibrosis%肾小管上皮间充质转化与肾脏纤维化

    Institute of Scientific and Technical Information of China (English)

    王来亮; 罗群

    2014-01-01

    Epithelial-mesenchymal transition ( EMT) , a process by which differentiated epithelial cells under-go a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury.However, the degree to which renal tubular epithelial EMT contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent.Renal tubular EMT is an adap-tive response of epithelial cells to a hostile or changing microenvironment and is regulated by many factors.Several intrace-llular signal transduction pathways such as transforming growth factor-β( TGF-β)/Smad and Wnt/β-catenin signaling are essential in controlling the process of renal tubular epithelial EMT which are potential targets of antifibrotic therapy present-ly.This review highlights the current understanding of renal tubular epithelial EMT and its underlying mechanisms to stimu-late further discussion on its role in the pathogenesis of renal interstitial fibrosis.

  17. RENAL TUBULAR SENSITIVITY TO ATRIAL-NATRIURETIC-FACTOR IN ESSENTIAL-HYPERTENSION

    NARCIS (Netherlands)

    JANSSEN, WMT; DEZEEUW, D; VANDERHEM, GK; DEJONG, PE

    1994-01-01

    Objective: To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. Design: Nine healthy volunteers and six patients with essential hypertension were studied on four test

  18. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine; Rossing, Kasper; Hess, Georg

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding p...

  19. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    Science.gov (United States)

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  20. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Nicolás M Kouyoumdzian

    Full Text Available The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP on organic cation transporters (OCTs expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T, ANP, dopamine (DA, D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects.

  1. Cell cycle regulatory factors in juxta-tumoral renal parenchyma.

    Science.gov (United States)

    Petruşcă, Daniela Nicoleta; Petrescu, Amelia; Vrabie, Camelia; Niculescu, L; Jinga, V; Diaconu, Carmen; Braşoveanu, Lorelei

    2005-01-01

    The aim of this study was to evaluate regulatory cell cycle factors in juxta-tumoral renal parenchyma in order to obtain information regarding early primary changes occurred in normal renal cells. Specimens of juxta-tumoral renal parenchyma were harvested from the tumoral kidney in 10 patients with no history of treatment before surgery. The expression of p53, Bcl-2, Rb and PCNA was studied by immunohistochemical methods in paraffin-embedded tissues. The apoptotic status was evaluated by flow-cytometry analysis following propidium iodide incorporation. The p53 protein expression was recognized in most of the cases (80%) with different intensities. High intensity apoptotic process detected in juxta-tumoral parenchyma seemed to be p53 dependent and well correlated with the low Bcl-2 expression. 70% of cases were Rb positive. In this type of tissue Rb has only an anti-proliferative and anti-tumoral role. PCNA was present in half of the cases being low expressed due to the tissue regenerating mechanism. Our data suggest that the high intensity of programmed cell death in this type of tissue is supported by the status of cell regulatory factors that control this process. Previous studies have demonstrated that healthy renal tissue has neither apoptosis nor mitotic activity. Juxta-tumoral renal tissue is also displaying normal morphology and DNA content (diploidy) but the microenvironmental status induced by the tumor presence prompts cells to choose death rather than malignant transformation. Further studies are necessary to emphasize if these results have a clinical relevance for the outcome of therapeutical approaches in renal carcinomas.

  2. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Directory of Open Access Journals (Sweden)

    K J Kelly

    Full Text Available Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  3. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  4. In situ lactate dehydrogenase activity - a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    2016-01-01

    and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen (BUN) or renal histology. However, there is currently a lack of precise methods to directly assess renal injury state non-invasively. Hyperpolarized 13C-pyruvate magnetic resonance...

  5. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient’s Perceptions of Over-the-Counter Medications and Their Adverse Effects

    Directory of Open Access Journals (Sweden)

    Mark D. Salter

    2013-01-01

    Full Text Available We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient’s perception of over-the-counter (OTC medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them.

  6. Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis

    NARCIS (Netherlands)

    D. Mul (Dick); F.K. Grote (Floor); J.R. Goudriaan; S.M.P.F. de Muinck Keizer-Schrama (Sabine); J.M. Wit (Jan); W. Oostdijk (Wilma)

    2010-01-01

    textabstractBackground: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. Objective: To investigate the clinical, growth and laboratory parameters in children

  7. Lysosomal Changes in Renal Proximal Tubular Epithelial Cells of Male Sprague Dawley Rats Following Decalin Exposure

    Science.gov (United States)

    1990-01-01

    decalin-treated animal. Note large, pale, rcd-staining lysosome (-). An exfoliated epithelial cell can iu- seen in the tubular lumen containing large...photomicrograph contains an exfoliated epithelial cell (-) with enlarged, intact lysosomes. The tubule on the left half of the photomicrograph contains an...metabolism of proteins. In: Cytology , GH Bourne and JF Danielli (eds). Academ- The Kidney: Physiology and Pathophysiology, DW ic Press, NY, pp. 251-300. - ~- i :- d .L n .- 2

  8. Renal primitive neuroectodermal tumor: does age at diagnosis impact outcomes?

    Directory of Open Access Journals (Sweden)

    Mahkameh Zare

    2012-01-01

    Full Text Available Primitive n euroectodermal tumor (PNET of the kidney is a rare and highly malignant neoplasm. The median age for renal PNET is 27 years but it can be seen also in a wide age range between 3 and 78 years. We performed a Medline search for the term renal PNET and identified 79 cases up till December of 2010. We report here a new case of renal PNET and a literature review for published data for evaluation of clinicopathological prognostic factors, with an emphasis on prognosis in two groups of adults and children-adolescents: 18 years of age or under and over 18 years.

  9. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.

    Science.gov (United States)

    Ahad, Amjid; Ahsan, Haseeb; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2015-10-05

    Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.

  10. Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

    Science.gov (United States)

    Altun, Demet; Kurekci, Ahmet Emin; Gursel, Orhan; Hacıhamdioglu, Duygu Ovunc; Kurt, Ismail; Aydın, Ahmet; Ozcan, Okan

    2014-10-01

    We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.

  11. Power doppler sonography in early renal transplantation: Does it differentiate acute graft rejection from acute tubular necrosis?

    Directory of Open Access Journals (Sweden)

    Haytham M Shebel

    2014-01-01

    Full Text Available To evaluate the role of power Doppler in the identification and differentiation bet-ween acute renal transplant rejection and acute tubular necrosis (ATN, we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sono-graphy. Assessment of cortical perfusion (CP by power Doppler was subjective, using our grading score system: P0 (normal CP; homogenous cortical blush extending to the capsule, P1 (reduced CP; cortical vascular cut-off at interlobular level, P2 (markedly reduced CP; scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr, and resistive index (RI. For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01 as well as between CP grading and RI (P <0.05. CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.

  12. Extracellular vesicles released from mesenchymal stromal cells modulate miRNA in renal tubular cells and inhibit ATP depletion injury.

    Science.gov (United States)

    Lindoso, Rafael S; Collino, Federica; Bruno, Stefania; Araujo, Dayana S; Sant'Anna, Julliana F; Tetta, Ciro; Provero, Paolo; Quesenberry, Peter J; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Camussi, Giovanni

    2014-08-01

    The mechanisms involved in renal repair by mesenchymal stromal cells (MSCs) are not entirely elucidated. The paracrine secretion of bioactive molecules has been implicated in the protective effects. Besides soluble mediators, MSCs have been shown to release extracellular vesicles (EVs), involved in renal repair process for different injury models. EVs have been shown to mediate communication between cells through the transference of several molecules, like protein, bioactive lipids, mRNA, and microRNAs (miRNAs). The miRNAs are noncoding RNAs that posttranscriptionally modulate gene expression and are involved in the regulation of several cellular processes, including those related to repair. The aim of the present study was to investigate the role of MSC-EVs in the modulation of miRNAs inside renal proximal tubular epithelial cells (PTECs) in an in vitro model of ischemia-reperfusion injury induced by ATP depletion. In this model we evaluated whether changes in miRNA expression were dependent on direct miRNA transfer or on transcription induction by MSC-EVs. The obtained results showed an enhanced incorporation of MSC-EVs in injured PTECs with protection from cell death. This biological effect was associated with EV-mediated miRNA transfer and with transcriptional modulation of miRNAs expressed by injured PTECs. Prediction of miRNA targets showed that miRNAs modulated in PTECs are involved in process of renal recovery with downregulation of coding-mRNAs associated with apoptosis, cytoskeleton reorganization, and hypoxia, such as CASP3 and 7, SHC1 and SMAD4. In conclusion, these results indicate that MSC-EVs may transfer and modulate the expression of several miRNAs involved in the repair and recovery process in PTECs.

  13. Genetics Home Reference: SLC4A1-associated distal renal tubular acidosis

    Science.gov (United States)

    ... a shortage of red blood cells ( anemia ). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), ... breakdown of these abnormal red blood cells may lead to hemolytic anemia. Some people have nonhereditary forms of distal renal ...

  14. Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Kanstrup, I L

    1993-01-01

    , heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P

  15. Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

    Science.gov (United States)

    Nielsen, A H; Knudsen, F; Danielsen, H; Pedersen, E B; Fjeldborg, P; Madsen, M; Brøchner-Mortensen, J; Kornerup, H J

    1987-02-01

    In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

  16. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P .... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  17. Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Fogh-Andersen, N; Strandgaard, S

    1996-01-01

    1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo.......3-31.0)% (P sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P

  18. Activation of SUR2B/Kir6.1-type KATP channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage

    Institute of Scientific and Technical Information of China (English)

    Ying ZHAO; Hai WANG

    2012-01-01

    Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure.Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (KATP) in the endothelium.It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium,glomerular mesangium,and the endothelium and the smooth muscle of blood vessels.Herein,we hypothesized that activating renal KATP channels with iptakalim might have directly neroprotective effects.In this study,glomerular endothelial,mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h.0.25 μl/ml OA could cause cellular damage of glomerular endothelium and mesangium,while 1.25μl/ml OA could lead to the injury of three types of renal cells.It was observed that pretreatment with iptakalim at concentrations of 0.1,1,10 or 100 μmol/L prevented cellular damage of glomerular endothelium and tubular epithelium,whereas iptakalim from 1 to 100 μmol/L prevented the injury of mesangial cells.Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner,significantly antagonized by glibenclamide,a KATP blocker.Iptakalim played a protective role in the main cell types of kidney,which was consistent with natakalim,a highly selective SUR2B/Kir6.1 channel opener.Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels,suggesting a new strategy for renal injury by its endothelial and renal cell protection.

  19. Renal mixed epithelial and stromal tumor: case report

    Directory of Open Access Journals (Sweden)

    Karla Lais Pêgas

    2015-02-01

    Full Text Available Mixed epithelial and stromal tumor (MEST represents a recently described biphasic kidney neoplasm, which predominantly affects perimenopausal females. The authors report the case of a young male patient with a MEST exhibiting positivity for estrogen and progesterone receptors. Computed tomography/magnetic resonance imaging (CT/MRI showed an expansive lesion affecting the right kidney. Grossly, a solid-cystic tumor was identified, which measured 5.7 × 3.5 × 2.4 cm. On microscopic examination, a biphasic tumor constituted by stromal and epithelial elements, without significant atypias, was identified. The stromal element was composed of spindle cells revealing positive immunoexpression for actin, desmin, vimentin, and estrogen receptors. The epithelial component exhibited a predominantly tubular pattern showing positive immunoreaction for cytokeratins. The diagnosis of MEST was then established.

  20. Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

    Directory of Open Access Journals (Sweden)

    Rink Nikki

    2012-01-01

    Full Text Available Hereditary distal renal tubular acidosis (dRTA is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1 expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.

  1. L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

    Directory of Open Access Journals (Sweden)

    Shujue Li

    2016-08-01

    Full Text Available Background/Aims: The interactions between calcium oxalate monohydrate (COM crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Methods: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. Results: Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1 shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. Conclusions: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.

  2. LEFT RENAL TUMOR: A RARE CADAVERIC FINDINGS

    Directory of Open Access Journals (Sweden)

    Siva Prasad

    2015-08-01

    Full Text Available A benign tumour is a non - cancerous growth that does not spread (metastasize to other parts of the body and is not usually life - threatening. Many researchers believe that most of the following types of kidney tumours are benign. However, others feel that some of these tumours have the potential to develop into renal cell carcinoma. There are no diagnostic tests that can confirm if a benign tumour has the potential to become cancerous. Benign tumours are sometimes found along with renal cell carcinoma when a removed kidney is examined by a pathologist. For these reasons, benign kidney tumours are treated like malignant tumours. In this case we have observed a male cadaver with a large tumour in the left kidney during our routine dissections of undergraduates .

  3. Pentavalent antimonial nephrotoxicity in the rat Disfunção tubular renal em ratos tratados com antimoniais pentavalentes

    Directory of Open Access Journals (Sweden)

    Joel Paulo R. Veiga

    1990-08-01

    Full Text Available Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia or Pentostam (Sodium Stibogluconate, Wellcome. In dose of 30 mg of Sb v (Glucantime or Pentostam by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day showed the functional and the histopathological alterations of the acute tubular necrosis.Estudou-se a função renal de ratos tratados com Glucantime (Antimoniato de Meglumine, Rhodia e Pentostam (Estibogluconato de Sódio, Wellcome na dose de 30 mg de Sb v por 100 g de peso por dia, durante 30 dias. Observou-se um distúrio na concentração urinária, que foi reversível 7 dias após cessada a administração das drogas. O estudo histopatológico do rim, por meio da microscopia óptica, não evidenciou alterações significativas. Por outro lado, ratos tratados com altas doses dos antimoniais (200 mg de Sb v por 100 g de peso por dia mostraram alterações funcionais e histopatológicas renais compatíveis com necrose tubular aguda.

  4. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.

    Directory of Open Access Journals (Sweden)

    Shiyo Muratsu-Ikeda

    Full Text Available BACKGROUND: Oxidative stress and endoplasmic reticulum (ER stress play a crucial role in tubular damage in both acute kidney injury (AKI and chronic kidney disease (CKD. While the pathophysiological contribution of microRNAs (miRNA to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. METHODS: We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2 gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. CONCLUSIONS: miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules.

  5. Serum level of proximal renal tubular epithelial cell-binding immunoglobulin G in patients with lupus nephritis.

    Science.gov (United States)

    Yap, D Y H; Yung, S; Zhang, Q; Tang, C; Chan, T M

    2016-01-01

    In vitro data showed that immunoglobulin G (IgG) from lupus nephritis (LN) patients could bind to proximal renal tubular epithelial cells (PTEC), but the clinical relevance of such binding remained unclear. Binding of IgG and subclasses to PTEC was measured by cellular ELISA (expressed as OD index) in 189 serial serum samples from 23 Class III/IV ± V LN patients who had repeated renal flares (48 during renal flares, 141 during low level disease activity (LLDA)), and compared with 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals. Total IgG PTEC-binding index was 0.34 ± 0.16, 0.29 ± 0.16, 0.62 ± 0.27 and 0.83 ± 0.38 in healthy controls, NLGD, LN patients during LLDA, and LN patients during nephritic flare, respectively (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). PTEC-binding index for IgG1 was 0.09 ± 0.05, 0.16 ± 0.12, 0.44 ± 0.34 and 0.71 ± 0.46 for the corresponding groups (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). Sixteen of 48 episodes (33.3%) of nephritic flare showed persistent PTEC-binding IgG seropositivity for more than 9.4 ± 3.1 months, despite clinical response to immunosuppressive treatment. Total IgG and IgG1 PTEC-binding correlated with anti-dsDNA level (r = 0.34 and 0.52, respectively, p < 0.001 for both), and inversely with C3 level (r = -0.26 and -0.50, respectively, p = 0.002 and<0.001). Sensitivity/specificity of PTEC-binding index in detecting renal flares was 45.8%/80.1% for total IgG (ROC AUC 0.630, p = 0.007) and 87.5%/35.5% for IgG1 (ROC AUC 0.615, p = 0.018). IgG1 PTEC-binding index correlated with tubulo-interstitial inflammation score in renal biopsy from corresponding patients. Our data suggested that total IgG and IgG1 PTEC-binding index in serum of LN patients correlate with serological activity, and in combination could predict renal flares. The correlation between IgG1

  6. Radiological features of progressive tumoral calcinosis in chronic renal failure.

    LENUS (Irish Health Repository)

    Hodnett, P

    2012-02-03

    We present the case of a young adult patient with chronic renal failure who developed painful subcutaneous nodules after failed renal transplant and recommencing dialysis. These nodules were juxta-articular in location and initially located over both shoulders. Radiological evaluation suggested tumoral calcinosis. The patient was placed on a strict dialysis and dietary regimen but was suboptimally compliant with same. The patient developed progressive disease with an increase in size and number of juxta-articular calcified soft-tissue masses. However, 6 months following a second renal transplant clinical and radiological follow up demonstrated marked resolution both in symptomatology and radiographic findings. We present the plain radiographic, CT and MRI findings which demonstrate the typical radiological features of tumoral calcinosis. We correlate these findings with clinical course and histological findings following surgical excision of one of these masses.

  7. An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis.

    Science.gov (United States)

    Morris, R C

    1968-07-01

    In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO(3) (-)) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO(3) (-)) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO(3) (-) of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H(+) secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO(3) (-) (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid.A reduced H(+) secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO(3) (-) was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal.

  8. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    Science.gov (United States)

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  9. Effects of Escherichia Coli Subtilase Cytotoxin and Shiga Toxin 2 on Primary Cultures of Human Renal Tubular Epithelial Cells

    Science.gov (United States)

    Márquez, Laura B.; Velázquez, Natalia; Repetto, Horacio A.; Paton, Adrienne W.; Paton, James C.; Ibarra, Cristina; Silberstein, Claudia

    2014-01-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2. PMID:24466317

  10. Resveratrol ameliorates hyperglycemia-induced renal tubular oxidative stress damage via modulating the SIRT1/FOXO3a pathway.

    Science.gov (United States)

    Wang, Xueling; Meng, Linghang; Zhao, Long; Wang, Zengfu; Liu, Haiying; Liu, Gang; Guan, Guangju

    2017-04-01

    Oxidative stress plays an important role in the development and progression of diabetic nephropathy (DN). We aimed to investigate if resveratrol (RSV) could ameliorate hyperglycemia-induced oxidative stress in renal tubules via modulating the SIRT1/FOXO3a pathway. The effects of RSV on diabetes rats were assessed by periodic acid-Schiff, Masson staining, immunohistochemistry, and western blot analyses. Additionally, oxidative indicators (such as catalase, superoxide dismutase, reactive oxygen species, and malondialdehyde), the deacetylase activity of SIRT1 and protein expressions of SIRT1, FOXO3a, and acetylated-FOXO3a were measured. These indicators were similarly evaluated in an in vitro study. Furthermore, the silencing of SIRT1 was used to confirm its role in the resistance to oxidative stress and the relationship between SIRT1 and FOXO3a in vitro. After 16weeks of RSV treatment, the renal function and glomerulosclerosis of rats with DN was dramatically ameliorated. RSV treatment increased SIRT1 deacetylase activity, subsequently decreasing the expression of acetylated-FOXO3a and inhibiting the oxidative stress caused by hyperglycemia both in vivo and in vitro. The silencing of SIRT1 in HK-2 cells aggravated the high glucose-induced oxidative stress and overexpression of acetylated-FOXO3a; RSV treatment failed to protect against these effects. RSV modulates the SIRT1/FOXO3a pathway by increasing SIRT1 deacetylase activity, subsequently ameliorating hyperglycemia-induced renal tubular oxidative stress damage. This mechanism provides the basis for a new approach to developing an effective DN treatment, which is of great clinical significance for reducing the morbidity and mortality associated with DN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on primary cultures of human renal tubular epithelial cells.

    Directory of Open Access Journals (Sweden)

    Laura B Márquez

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC cause post-diarrhea Hemolytic Uremic Syndrome (HUS, which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC and compare its effects with those produced by Shiga toxin type 2 (Stx2, in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.

  12. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney ston

  13. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney ston

  14. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, M; Harmsen, MC; Koerts, JA; Petersen, AH; van Luyn, MJA; Navis, G; Popa, ER

    2005-01-01

    Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned

  15. Effect of Diuretics on Renal Tubular Transport of Calcium and Magnesium

    DEFF Research Database (Denmark)

    Alexander, R Todd; Dimke, Henrik

    2017-01-01

    of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na+) transport, but also indirectly affect renal Ca2+ and Mg2+ handling, i.e. by establishing a prerequisite electrochemical gradient...

  16. 肾小管损伤治疗的研究进展%Progress of the treatment on renal tubular injury

    Institute of Scientific and Technical Information of China (English)

    林金爱

    2013-01-01

    A variety of kidney diseases have different degree of renal tubular injury,it even occur before the kidney damage.Since renal tubular injury still lack of effective therapy,it usually recovered by renal tubular epithelial cell itself.But the self-recover process is too long.If it is unable to spend this period,renal damage may not be reversible.So effective therapy is an emergency problem to be solved in clinical.%临床上多种肾脏疾病均有不同程度的肾小管损伤,甚至在肾脏受损前已出现肾小管病变.至今肾小管损伤尚缺乏有效的治疗手段,通常等待肾小管上皮细胞的自身恢复,这一过程较漫长,若无法渡过这一时期,肾损伤可能无法逆转.因此,寻求有效的治疗手段是临床急待解决的问题.

  17. Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

    Directory of Open Access Journals (Sweden)

    Menegon L.F.

    1998-01-01

    Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

  18. Renal Cell Carcinoma Mimicking Adrenal Tumor

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Moslemi

    2010-01-01

    Full Text Available There are a variety of causes of adrenal pseudotumors on computerized tomography (CT scan, including upper-pole renal mass, gastric diverticulum, prominent splenic lobulation, pancreatic mass, hepatic mass, and periadrenal varices. We present a case of a large subhepatic mass that discrimination of its origin from neighborhood organs was difficult preoperatively. Our patient was a 58 years old man, that three months after an unsuccessful operation in another center for a pseudoadrenal mass underwent a very difficult subcapsular tumorectomy in our center.

  19. Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

    Science.gov (United States)

    Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2016-03-01

    Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix.

  20. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

    Science.gov (United States)

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer

    2003-02-01

    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  1. Renal inflammatory myofibroblastic tumor - a new case report.

    Science.gov (United States)

    Petrescu, Amelia; Berdan, Gabriela; Hulea, Ionela; Gaitanidis, Raluca; Ambert, V; Jinga, V; Popescu, M; Andrei, F; Niculescu, L

    2007-01-01

    Renal inflammatory pseudotumor is uncommon, benign tumor that has been classified into separate group but there is a risk that this lesion could be misdiagnosed. The aim of this work is to report a new case of 57-years-old man presented in our hospital with hematuria, minimal grade fever and right flank pain. Magnetic resonance imaging (MRI) and sonography revealed a tumor of the right mediorenal parenchyma, 2.5 cm in diameter. The patient underwent right nephroureterectomy under the diagnosis of renal cell carcinoma. Macroscopically examination carried out on the removed kidney showed a 2/2/1.5 cm yellowish, gelatinous, well circumscribed, mediorenal and pericaliceal mass. Fragments of the tumor were fixed in 10% formaldehyde, included in paraffin, and the sections were stained with HE, VG and immunohistochemically with vimentin (VIM), MNF116, SyN, smooth muscle actin (ACT), desmin, CD68, S100, HMB45, and CD117. The histological examination revealed a compact spindle cell proliferation, a hypocellular fibrous area in an edematous myxoid background infiltrated by small lymphocytes, histiocytes, some plasma cells and small bone area. The spindle cells were diffuse positive for VIM, ACT, CD68 and negative for desmin, MNF116, SyN, S100, HMB45, and CD117. The pathologic diagnosis was renal inflammatory pseudotumor, raising the problem of differential diagnosis, as the clinical and imagistic aspects are similar to those of a renal carcinoma and the problem in establishing a preoperative correct diagnosis.

  2. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3

    OpenAIRE

    Fenton, Robert A.; Poulsen, Søren B.; de la Mora Chavez, Samantha; Soleimani, Manoocher; Busslinger, Meinrad; Dominguez Rieg, Jessica A.; Rieg, Timo

    2015-01-01

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation, resul...

  3. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

    Directory of Open Access Journals (Sweden)

    Kohan Donald E

    2002-08-01

    Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

  4. A rare renal pelvis tumor: Mucinous cystadenocarcinoma

    Directory of Open Access Journals (Sweden)

    Gül Türkcü

    2015-03-01

    Full Text Available Urothelial carcinomas are the most common neoplasms in the renal pelvis. However mucinous cystadenocarcinomas (MCA are very rare in this localization. Although some theories are attributed on the patogenesis of MCA, its exact etiology is not known. Herein, we present histopathological characteristic of a case with MCA. Multiple cystic lesions and millimetric calculi with ectasia of the left kidney were detected by abdominal ultrasound and magnetic resonance imaging. Left simple nephrectomy was performed because of a pre-diagnosis of atrophic pyonephrotic kidney. The sections of the nephrectomized kidney revealed, multilocular mucinous cysts and histopathological appearance of MCA. We aimed to present this rare case mimicking atrophic cystic kidney with clinical, radiological findings, and histopathological characteristics in the lights of literature.J Clin Exp Invest 2015; 6(1: 78-80

  5. Pathology of spontaneous tubular proteinuria evaluated by renal scintigraphy {sup 99m}-Tc-dimercaptosuccinic acid (DMSA). Second report. Evaluation of urinary excretion and urinary bladder uptake images

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takeshi; Hosaki, Tomoko; Shimizu, Mariko [Fussa Hospital, Tokyo (Japan)] [and others

    2000-03-01

    The significance of DMSA uptake in the urinary bladder and %uptake in renal scintigrams with {sup 99m}Tc-DMSA in spontaneous tubular proteinuria was reassessed. The subjects were 10 patients in whom DMSA uptake in the urinary bladder could be clearly evaluated among 15 cases that were tentatively diagnosed as having spontaneous tubular proteinuria and in which renal scintigraphy was performed with DMSA. All of the patients were male children and their mean age was 9 years 11 months. No morphological abnormalities in the kidneys could be detected in any of the cases, and %uptake of DMSA was very low. Urinary excretion and uptake of the nuclide in the urinary bladder was significantly increased. In view of the pharmacokinetics of DMSA, the patients' disease appeared to be complicated by failure of the proximal tubule epithelial cells to resorb low-molecular-weight proteins, and the failure of active transport on the vascular lumen side of the cells. As a result, urinary excretion was increased and marked uptake in the urinary bladder was induced. Accordingly, when %uptake of DMSA cannot be measured, it is necessary to determine the extent of uptake in the urinary bladder. When images showing abnormal uptake are obtained, the possibility of diseases associated with functional failure at the proximal tubular level, such as spontaneous tubular proteinuria, is quite high. (K.H.)

  6. Hypokalemia-Induced Rhabdomyolysis as a result of Distal Renal Tubular Acidosis in a Pregnant Woman: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Manasawee Srisuttayasathien

    2015-01-01

    Full Text Available Rhabdomyolysis in pregnancy is a rare occurrence. The manifestation of distal renal tubular acidosis (RTA for the first time during adulthood is uncommon. According to a review of the literature, pregnancy may predispose individuals to rhabdomyolysis due to hypokalemia. A reduction in interstitial potassium ions could decrease muscular blood flow and lead to muscle injury. This report describes the case of a pregnant woman with rhabdomyolysis induced by hypokalemia resulting from distal RTA. The patient subsequently delivered a healthy newborn.

  7. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility...... at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion...

  8. Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Francisco O'Valle

    Full Text Available UNLABELLED: Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD transplantation. Ischemia-reperfusion (IR injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1 activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls and in murine Parp-1 knockout model of IR injury. RESULTS: PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603, time to effective diuresis (r = 0.770, serum creatinine levels at biopsy (r = 0.649, and degree of ATN (r = 0.810 (p = 0.001, Pearson test. In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

  9. Influence of consumption of cadmium-polluted rice or Jinzu River water on occurrence of renal tubular dysfunction and/or Itai-itai disease.

    Science.gov (United States)

    Kobayashi, Etsuko; Suwazono, Yasushi; Dochi, Mirei; Honda, Ryumon; Kido, Teruhiko

    2009-03-01

    The aim of this study was to clarify whether consumption of cadmium (Cd)-polluted rice or Jinzu River water exerted any influence on the occurrence of renal tubular dysfunction and/or Itai-itai disease. From the participants of health examinations conducted in 1967 and 1968, 3,078 subjects who had resided for >30 years in the present hamlet and were aged >50 years were selected as the target population and were divided according to their residence in 55 hamlets. In a multiple regression analysis, the regression coefficients between rice-Cd concentration and prevalence of abnormal urinary findings (proteinuria, glucosuria, or proteinuria with glucosuria) or patients with Itai-itai disease were statistically significant between both sexes. The correlation between the prevalence of users of Jinzu River water and the occurrence of glucosuria in men as well as abnormal urinary findings in women was not statistically significant. We surmise that eating Cd-polluted rice and drinking and/or cooking with Jinzu River water influenced the occurrence of Itai-itai disease. The occurrence of renal tubular dysfunction is likely to have also been influenced by both factors, with eating Cd-polluted rice having a greater impact on the occurrence of renal tubular dysfunction as compared to drinking and/or cooking with Jinzu River water.

  10. Cobalt Chloride Induces Expression and Function of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Renal Proximal Tubular Epithelial Cell Line HK-2.

    Science.gov (United States)

    Nishihashi, Katsuki; Kawashima, Kei; Nomura, Takami; Urakami-Takebayashi, Yumiko; Miyazaki, Makoto; Takano, Mikihisa; Nagai, Junya

    2017-01-01

    The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2. Cobalt chloride treatment significantly increased the mRNA expression of not only glucose transporter 1 (GLUT1), a typical HIF-1 target gene mRNA, but also ABCG2 mRNA in HK-2 cells. The BCRP inhibitor Ko143-sensitive accumulation of BCRP substrates such as Hoechst33342 and mitoxantrone was significantly enhanced by cobalt chloride treatment. In addition, treatment with cobalt chloride significantly increased the Ko143-sensitive accumulation of fluorescein isothiocyanate-labeled methotrexate in HK-2 cells. Furthermore, cobalt chloride treatment attenuated the cytotoxicity induced by mitoxantrone and methotrexate, which might be, at least in part, due to the increase in BCRP-mediated transport activity via HIF-1 activation. These findings indicate that HIF-1 activation protects renal proximal tubular cells against BCRP substrate-induced cytotoxicity by enhancing the expression and function of BCRP in renal proximal tubular cells.

  11. A single nucleotide polymorphism in kidney anion exchanger 1 gene is associated with incomplete type 1 renal tubular acidosis

    Science.gov (United States)

    Takeuchi, Takumi; Hattori-Kato, Mami; Okuno, Yumiko; Kanatani, Atsushi; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    Various conditions including distal renal tubular acidosis (dRTA) can induce stone formation in the kidney. dRTA is characterized by an impairment of urine acidification in the distal nephron. dRTA is caused by variations in genes functioning in intercalated cells including SLC4A1/AE1/Band3 transcribing two kinds of mRNAs encoding the Cl−/HCO3− exchanger in erythrocytes and that expressed in α-intercalated cells (kAE1). With the acid-loading test, 25% of urolithiasis patients were diagnosed with incomplete dRTA. In erythroid intron 3 containing the promoter region of kAE1, rs999716 SNP showed a significantly higher minor allele A frequency in incomplete dRTA compared with non-dRTA patients. The promoter regions of the kAE1 gene with the minor allele A at rs999716 downstream of the TATA box showed reduced promoter activities compared that with the major allele G. Patients with the A allele at rs999716 may express less kAE1 mRNA and protein in the intercalated cells, developing incomplete dRTA. PMID:27767102

  12. Epinephrine Evokes Renalase Secretion via a-Adrenoceptor/NF-κB Pathways in Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2014-08-01

    Full Text Available Background/Aims: Renalase is a recently discovered, kidney-specific monoamine oxidase that metabolizes circulating catecholamines. These findings present new insights into hypertension and chronic kidney diseases. Previous data demonstrated that renalase was mainly secreted from proximal tubules which could be evoked by catecholamines. The purpose of this study is to investigate whether renalase expression is induced by epinephrine via a-adrenoceptor/NFκB pathways. Methods: HK2 cells were utilized to explore renalase expression in response to epinephrine in vitro. Phentolamine, an a-adrenoceptor antagonist, and Tosyl Phenylalanyl Chloromethyl Ketone (TPCK were used to block a-adrenoceptor and to knock down the transcription factor NFκB, respectively. Renalase expression was analyzed using Western blot and quantitative PCR. Results: Both protein and mRNA levels of renalase in HK2 cells increased in response to epinephrine (PConclusion: Epinephrine evokes renalase secretion via a-adrenoceptor/NF-κB pathways in renal proximal tubular epithelial cells.

  13. Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.

    Science.gov (United States)

    Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

    2002-04-25

    Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.

  14. Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Stain with Antibodies for Bovine Papillomavirus Type 1 L1 Protein

    Directory of Open Access Journals (Sweden)

    Elizabeth McInnes

    2015-06-01

    Full Text Available The kidneys from six immunodeficient mice examined by Cerberus Sciences and the Animal Resources Centre, displayed karyomegaly with pale eosinophilic, intranuclear inclusions upon histopathological examination. Electron microscopy performed on kidney tissue from 5/6 mice demonstrated margination of the chromatin in large nuclei. Laboratory tests were used to detect nucleic acid of papillomaviruses, polyomaviruses, circoviruses and anelloviruses (4/6 mice, a specific PCR was used to detect murine polyomavirus (1/6, and a panel of serological tests was used to detect seroconversion to major murine pathogens (1/6. All molecular and serological tests were negative. Immunohistochemistry using polyclonal anti-bovine papillomavirus type 1 (BPV-1 L1 antibody, Camvir monoclonal anti-papillomavirus antibody (directed against the seven amino acids GFGAMDF found in human papillomavirus (HPV 16 L1 protein, a commercially available mixture of two monoclonal antibodies, anti-BPV-1 L1/1H8 + Camvir antibodies, and a monoclonal anti-Hsc70 antibody revealed specific, positive staining of murine renal tubular epithelial intranuclear inclusions in 6/6 mice using the anti-BPV-1 L1 containing antibodies only. Methyl pyronin green, PAS and Feulgen histochemical reactions revealed that the intranuclear inclusions did not consist of RNA, DNA or carbohydrate. An immunohistochemical method now exists that can be used to confirm and evaluate suspected cases of murine inclusion body nephropathy.

  15. 'Endotoxin tolerance': TNF-alpha hyper-reactivity and tubular cytoresistance in a renal cholesterol loading state.

    Science.gov (United States)

    Zager, R A; Johnson, A C M; Lund, S

    2007-03-01

    The term 'endotoxin tolerance' defines a state in which prior endotoxin (lipopolysaccharide (LPS)) exposure induces resistance to subsequent LPS attack. However, its characteristics within kidney have not been well defined. Hence, this study tested the impact of LPS 'preconditioning' (LPS-PC; 18 or 72 h earlier) on: (i) selected renal inflammatory mediators (tumor necrosis factor (TNF)-alpha, interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), Toll-like receptor 4 (TLR4); protein or mRNA); (ii) cholesterol homeostasis (a stress reactant); and (iii) isolated proximal tubule (PT) vulnerability to hypoxia or membrane cholesterol (cholesterol oxidase/esterase) attack. Two hours post LPS injection, LPS-PC mice manifested reduced plasma TNF-alpha levels, consistent with systemic LPS tolerance. However, in kidney, paradoxical TNF-alpha hyper-reactivity (protein/mRNA) to LPS existed, despite normal TLR4 protein levels. PT TNF-alpha levels paralleled renal cortical results, implying that PTs were involved. LPS-PC also induced: (i) renal cortical iNOS, IL-10 (but not MCP-1) mRNA hyper-reactivity; (ii), PT cholesterol loading, and (iii) cytoresistance to hypoxia and plasma membrane cholesterol attack. A link between cholesterol homeostasis and cell LPS responsiveness was suggested by observations that cholesterol reductions in HK-2 cells (methylcyclodextrin), or reductions in HK-2 membrane fluidity (A2C), blunted LPS-mediated TNF-alpha/MCP-1 mRNA increases. In sum: (i) systemic LPS tolerance can be associated with renal hyper-responsiveness of selected components within the LPS signaling cascade (e.g., TNF-alpha, iNOS, IL-10); (ii) PT cytoresistance against hypoxic/membrane injury coexists; and (iii) LPS-induced renal/PT cholesterol accumulation may mechanistically contribute to each of these results.

  16. Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

    Institute of Scientific and Technical Information of China (English)

    张春; 孟宪芳; 朱忠华; 杨晓; 邓安国

    2004-01-01

    Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.

  17. Renal Function Recovery after Nephrectomy or Nephron-Sparing Surgery in Children with Unilateral Renal Tumor.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Cozzi, Francesco

    2017-02-01

    Introduction Children with unilateral renal tumor (URT) and preoperative renal dysfunction (PRD) may benefit from nephron-sparing surgery (NSS). To test this hypothesis, we studied the outcome of baseline renal function after nephrectomy or NSS among children with URT. Materials and Methods Retrospective records review of children with URT who underwent nephrectomy (25 children) or NSS (11 children) at our institution. We analyzed the estimated glomerular filtration rate (eGFR) changes over time among patients, stratified by both preoperative renal function (with or without PRD) and surgical extent (NSS vs. nephrectomy). The primary end point was evaluation of compensatory recovery of preoperative eGFR after surgery. Only children older than 2 years at surgery were included in the study. Renal dysfunction was defined as an eGFR  100 mL/min/1.73 m(2), respectively, achieved or maintained two-kidney eGFR values (T-KEV) (p = 0.01). After NSS, four adolescent patients with PRD and seven without PRD achieved or maintained T-KEV. Conclusion The majority of children with URT and low baseline eGFR present with an impaired renal function recovery after nephrectomy and may benefit from NSS. Collaborative studies are needed to support present findings. Georg Thieme Verlag KG Stuttgart · New York.

  18. Core biopsies of renal tumors: A study on diagnostic accuracy, interobserver, and intraobserver variability

    DEFF Research Database (Denmark)

    Kummerlin, I.; Kate, F. ten; Smedts, F.;

    2008-01-01

    Objective: The diagnostic accuracy of in-bench core biopsies (CBs) from renal masses, and the interobserver and intraobserver variability in pathological subtyping of renal tumors were assessed. Methods: We performed two CBs in 62 consecutive renal masses suspected for renal cell carcinoma (RCC...

  19. 肾小管上皮细胞损伤的研究进展%Progress in research of renal tubular epithelial cell injury

    Institute of Scientific and Technical Information of China (English)

    彭单单

    2013-01-01

    肾小管上皮细胞(RTEC)是肾小管间质的主要细胞,具有旺盛的代谢活性和潜在的增殖能力,并能分泌多种细胞因子.RTEC损伤,不仅是引起急性肾衰竭的直接原因,而且是导致慢性肾衰竭、贫血、肾性骨病等不可逆的终末期肾病的主要原因和共同病理过程.防治RTEC损伤对于减缓或逆转肾间质纤维化进展具有重要意义.%Renal tubular epithelial cell (RTEC) is the major cell type in renal tubulointerstitium. It has strong metabolic activity and proliferative potency. It secretes a variety of cytokines. RTEC injury is not only the direct cause of acute renal failure, but also the main reason of renal interstitial fibrosis (RIF) and the common pathological process of irreversible end-stage renal diseases such as chronic renal failure, anemia and renal osteodystrophy. Prevention and treatment of RTEC injury is of great significance in slowing down and reversing the progress of RIF.

  20. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3.

    Science.gov (United States)

    Fenton, Robert A; Poulsen, Søren B; de la Mora Chavez, Samantha; Soleimani, Manoocher; Busslinger, Meinrad; Dominguez Rieg, Jessica A; Rieg, Timo

    2015-06-15

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na(+)/H(+) exchanger isoform 3 (NHE3) localization and phosphorylation, resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2, and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605, or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na(+)/bicarbonate cotransporter NBCe1, pretreatment with DIDS inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis.

  1. Effect of low-osmolar contrast medium iopromide and iso-osmolar iodixanol on DNA fragmentation in renal tubular cell culture.

    Science.gov (United States)

    Ludwig, Ulla; Connemann, Julia; Keller, Frieder

    2013-12-01

    Intravascular administration of iodinated contrast media continues to be a common cause of hospital-acquired acute kidney injury. Accumulating evidence suggests that radiocontrast agent-induced nephrotoxicity is associated with increased oxidative stress, which leads to renal tissue damage with DNA fragmentation. We therefore tested whether an iso-osmolar contrast medium (iodixanol) causes less oxidative DNA damage to renal tubular cells than a low-osmolar contrast medium (iopromide). HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10 min-2 h) with increasing concentrations (20-120 mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis). Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2 h with 120 mg/ml iodine for iopromide (32 ± 27 tail moments) and iodixanol (46 ± 41 tail moments); both were significantly different from the control value with 3.15 ± 1.6 tail moments (Student's t test; p DNA fragmentation than iopromide (ANOVA for 1 h p = 0.039 and 2 h p = 0.025, respectively). We were able to demonstrate for the first time that an iso-osmolar contrast medium induced even greater oxidative stress and DNA damage than a low-osmolar agent in HK-2 cells. This could provide an explanation for the nephrotoxicity that also is observed with iodixanol in clinical practice.

  2. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

    Science.gov (United States)

    Rinaldo, Christine Hanssen; Gosert, Rainer; Bernhoff, Eva; Finstad, Solrun; Hirsch, Hans H

    2010-11-01

    Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC(90)) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC(90)s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells in vitro.

  3. Diagnostic problems in the subtyping of renal tumors encountered by five pathologists

    DEFF Research Database (Denmark)

    Kümmerlin, Intan; ten Kate, Fiebo; Smedts, Frank

    2009-01-01

    The diagnostic problems in the subtyping of renal tumors were evaluated by a panel of five pathologists studying a set of selected tumors. Five pathologists independently assessed a single hematoxylin-and-eosin (HE)-stained slide from 28 selected renal tumors. After this independent assessment...

  4. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  5. 黏液样小管状及梭形细胞肾癌的CT诊断%CT diagnosis of mucinous tubular and spindle cell renal carcinoma

    Institute of Scientific and Technical Information of China (English)

    王秀玲; 张宗军; 夏秋媛; 陆珍风; 季学满

    2016-01-01

    Objective:To discuss the CT manifestations of mucinous tubular and spindle cell renal carcinoma (MTSRCC)and to improve the understanding of this tumor.Methods:The CT features of 8 patients with surgery and pa-thology proven MTSRCC were retrospectively analyzed.Non-enhanced and triphasic enhanced CT scanning were performed in all of the 8 patients.The size,location,density in plain CT and the enhanced pattern and degree of the tumor,as well as the adjacent involvement,retroperitoneal lymph node and distant metastasis were analyzed.Results:All of the 8 patients with MTSRCC presented as single,well-defined,oval or round mass with the mean maximum diameter as 4.53cm (1.8 ~7.6cm).Iso-attenuation or slightly hyper-attenuation of the tumor was revealed on plain CT in 7 cases,and hypo-attenuation in 1 case.Association with nephrolithiasis in 1 case.No intra-tumoral hemorrhage or calcification was identified.Tumor showed as gradually mild enhancement after contrast administration,homogeneous enhancement was showed in 6 patients and heterogeneous enhancement in 2 patients.The enhancement degree was apparently less than that of normal renal cortex. The mean CT value of the tumor in these 8 patients increased at cortico-medullary phase and delayed phase was 26.2HU and 33.6HU respectively.The ratio of tumor and renal cortex in cortico-medullary phase and delayed phase was 21.54%and 33.28% respectively.Conclusion:MTSRCC is a rarely seen renal neoplasm with low degree malignancy,which predomi-nantly presents in adult women.The CT features include well-defined,mass,necrosis and calcification are seldom,could be associated with nephrolithiasis,iso-attenuated on plain CT and with progressively mild enhancement.%目的:探讨黏液样小管状及梭形细胞肾癌(MTSRCC)的 CT 表现,提高对该病的认识。方法:回顾性分析8例经手术病理证实的 MTSRCC 的 CT 表现,8例均行 MSCT 平扫及三期增强扫描。分析病灶大小、位置、形态、平

  6. Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method

    DEFF Research Database (Denmark)

    Abildgaard, U; Holstein-Rathlou, N H; Leyssac, P P

    1986-01-01

    The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium...... reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional...... lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during...

  7. Clear cell renal cell tumors: Not all that is "clear" is cancer.

    Science.gov (United States)

    Williamson, Sean R; Cheng, Liang

    2016-07-01

    Continued improvement of our understanding of the clinical, histologic, and genetic features of renal cell tumors has progressively evolved renal tumor classification, revealing an expanding array of distinct tumor types with different implications for prognosis, patient counseling, and treatment. Although clear cell renal cell carcinoma is unequivocally the most common adult renal tumor, there is growing evidence that some "clear cell" renal neoplasms, such as exemplified by multilocular cystic clear cell renal neoplasm of low malignant potential (formerly multilocular cystic renal cell carcinoma), do not have the same potential for insidious progression and metastasis, warranting reclassification as low malignant potential tumors or benign neoplasms. Still other novel tumor types such as clear cell papillary renal cell carcinoma have been more recently recognized, which similarly have shown a conspicuous absence of aggressive behavior to date, suggesting that these too may be recategorized as noncancerous or may be premalignant neoplasms. This importance for prognosis is increasingly significant in the modern era, in which renal masses are increasingly found incidentally by imaging techniques at a small tumor size, raising consideration for less aggressive management options guided by renal mass biopsy diagnosis, including imaging surveillance, tumor ablation, or partial nephrectomy.

  8. Chronic kidney disease in children with unilateral renal tumor.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Schiavetti, Amalia; Cozzi, Francesco

    2012-05-01

    In patients who have undergone nephrectomy lower stage chronic kidney disease may develop, which is an independent risk factor for cardiovascular disease and overall mortality. We investigated whether the prevalence of lower stage chronic kidney disease is related to the amount of renal parenchyma excised in children with unilateral renal tumor. A total of 15 patients treated with nephrectomy and 10 treated with nephron sparing surgery were enrolled at a single academic center. The Kidney Disease Outcomes Quality Initiative guidelines were used to classify patients by chronic kidney disease stage based on estimated glomerular filtration rate values. The Modification of Diet in Renal Disease study equation and Schwartz equation were used in patients older and younger than 17 years, respectively. At a mean followup of more than 12 years 8 patients who had undergone nephrectomy and 1 treated with bilateral nephron sparing surgery presented with stage II chronic kidney disease (estimated glomerular filtration rate 60 to 89 ml/min/1.73 m(2)). Sequential measurements from diagnosis to 12 to 17 years postoperatively showed that stage II chronic kidney disease in patients who had undergone nephrectomy manifested as a negligible postoperative increase in mean ± SD estimated glomerular filtration rate (75.7 ± 25.5 vs 79.4 ± 3.9 ml/min/1.73 m(2), p = 0.6). Five of the 8 patients presented with stage II chronic kidney disease even before nephrectomy. The other 7 patients who had undergone nephrectomy and those treated with nephron sparing surgery presented with a significant postoperative increase in mean ± SD estimated glomerular filtration rate (81.1 ± 24 vs 102.3 ± 3 ml/min/1.73 m(2), p = 0.02, and 88.7 ± 2 vs 107.4 ± 14 ml/min/1.73 m(2), p = 0.005, respectively). A subset of children with unilateral renal tumor presents before and/or after nephrectomy, and not after nephron sparing surgery, with stage II chronic kidney disease, probably due to a reduced renal

  9. Lin28 sustains early renal progenitors and induces Wilms tumor.

    Science.gov (United States)

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S; Zhu, Hao; Perez-Atayde, Antonio R; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q

    2014-05-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis.

  10. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Science.gov (United States)

    de Borst, Martin H; Nauta, Ferdau L; Vogt, Liffert; Laverman, Gozewijn D; Gansevoort, Ron T; Navis, Gerjan

    2012-01-01

    Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs) may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal) side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12) with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP)), patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID). Healthy subjects (n = 10) screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, pglomerulo- and tubulo-protective effects as observed outweigh the possible side-effects of NSAID treatment on the long term.

  11. Study on Effect of Baoyuan Qiangshen (保元强肾) Capsule No. Ⅱ on Tubular Interstitial Injury in Chronic Renal Failure Patients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the protective effect of Baoyuan Qiangshen Capsule No. Ⅱ (BYQS) and its mechanism in treating chronic renal failure (CRF). Methods: Sixty CRF patients were divided into 2 groups randomly, the treated group used BYQS combined with Lotensin and the control group administered with essential amino acid combined with Lotensin. Changes of renal functions and tubular labelled proteins were observed. Results: The markedly effective rate and total effective rate of the treated group were 63.3% and 93.3% respectively, and those of the control group were 30.0% and 56.7% respectively, the effect of the treated group was obviously better than that of the control group (P<0.01). In the treated group after medication, blood urea nitrogen, serum creatinine and clearance rate of creatinine were improved significantly (P<0.01), while Tamm-Horfau protein increased significantly (P<0.01). Conclusion: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF.

  12. Effects of supplemental recombinant bovine somatotropin and mist-fan cooling on the renal tubular handling of sodium in different stages of lactation in crossbred Holstein cattle.

    Science.gov (United States)

    Boonsanit, Dolrudee; Chanpongsang, Somchai; Chaiyabutr, Narongsak

    2012-08-01

    The effect of supplementary administration of recombinant bovine somatotrophin (rbST) on the renal tubular handling of sodium in crossbred 87.5% Holstein cattle housed in normal shade (NS) or mist-fan cooled (MF) barns was evaluated. The cows were injected with 500 mg rbST at three different stages of lactation. The MF barn housed cows showed a slightly decreased ambient temperature and temperature humidity index, but an increased relative humidity. Rectal temperature and respiration rates were significantly lower in cooled cows. The rbST treated cows, housed in NS or MF barns, showed markedly increased milk yields, total body water, extracellular fluid and plasma volume levels, along with a reduced rate of urine flow and urinary excretion of sodium, potassium and chloride ions and osmolar clearance, in all three stages of lactation. Renal tubular sodium and water reabsorption were increased after rbST administration without any alteration in the renal hemodynamics. Lithium clearance data suggested that the site of response is in the proximal nephron segment, which may be mediated via increases in the plasma levels of aldosterone and IGF-1, but not vasopressin, during rbST administration.

  13. Distal renal tubular acidosis in Filipino children, caused by mutations of the anion-exchanger SLC4A1 (AE1, Band 3) gene.

    Science.gov (United States)

    Anacleto, Francisco E; Bruce, Lesley J; Clayton, Peter; Hegde, Shivram; Resontoc, Lourdes P; Wrong, Oliver

    2010-01-01

    To describe the clinical features and genetic basis of distal renal tubular acidosis (dRTA) in Filipino children. Clinical description and gene analysis of affected members of 7 families. In all affected children, the disease was associated with mutations of the SLC4A1 gene that codes for the bicarbonate/chloride anion-exchanger 1 (AE1, band 3) protein situated in the red cell membrane and the alpha-intercalated (proton-secreting) cell of the renal collecting duct. In 2 families, affected children were homozygous for a substitution of aspartic acid for glycine in residue 701 of the AE1 protein (G701D); in the other 5 families, affected children were compound heterozygotes of this mutation with the AE1 mutation (Delta400-408) that causes Southeast Asian ovalocytosis (SAO). All affected children had morphological red cell changes that closely resembled SAO, including the children who were homozygous for G701D and did not have the SAO mutation. Homozygous G701D thus produces morphological red cell changes that are not readily distinguishable from SAO. The parents of all 7 families were originally domiciled in the islands of the Visayas group in the central part of the Philippine archipelago. Recessive renal tubular acidosis in Filipinos is usually caused by SLC4A1 mutations, commonly G701D. 2010 S. Karger AG, Basel.

  14. Insulin-like growth factor-1 enhances epidermal growth factor receptor activation and renal tubular cell regeneration in postischemic acute renal failure.

    Science.gov (United States)

    Lin, J J; Cybulsky, A V; Goodyer, P R; Fine, R N; Kaskel, F J

    1995-06-01

    Growth factors such as insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and hepatocyte growth factor have been shown to accelerate the recovery from postischemic acute renal failure (ARF) with a concomitant increase in DNA synthesis. Interactions between growth factors have been demonstrated in a number of in vitro studies. This study examined the effect of exogenous IGF-1 on the DNA synthesis and EGF receptor (EGF-R) activation in postischemic rat kidneys. Thirty minutes after the relief of 30-minute total occlusion of the left renal artery in anesthetized 225 to 300 gm Sprague-Dawley rats, either IGF-1 (75 micrograms/kg) or normal saline solution (NS, 0.2 ml) was given by intravenous bolus, followed by twice daily subcutaneous injections of IGF-1 (50 micrograms/kg) or 0.2 ml NS for 4 days, respectively, in IGF-1-Tx) and NS treated (NS-Tx) groups (n = 8 each). On the day after the completion of treatment, inulin clearance (ml/kg/min) of the postischemic kidneys in the IGF-1-Tx group was significantly higher (p < 0.01) than inulin clearance of kidneys in the NS-Tx group. This was associated with improved kidney morphology. IGF-1 treatment also enhanced the labeling index of 5-bromo-2'-deoxyuridine (percent of stained tubule cells), a marker for active DNA synthesis, in the outer medulla of postischemic kidneys at 1 day and 2 days after the injury. EGF-R tyrosine phosphorylation (which reflects receptor activation) increased in postischemic kidneys in both NS-Tx (n = 5) and IGF-1-Tx (n = 3) groups 1 day after the injury as compared with nonischemic contralateral kidneys. In the IGF-1-Tx group there was also increased iodine 125-labeled EGF binding and EGF-R protein. Our results demonstrate a beneficial effect of IGF-1 on postischemic ARF. Furthermore, they suggest that EGF-R activation is involved in tubular regeneration and that IGF-1 may enhance EGF-R activation by increasing EGF-R expression.

  15. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  16. Parathyroid hormone-mitogen-activated protein kinase axis exerts fibrogenic effect of connective tissue growth factor on human renal proximal tubular cells

    Institute of Scientific and Technical Information of China (English)

    GUO Yun-shan; YUAN Wei-jie; ZHANG Ai-ping; DING Yao-hai; WANG Yan-xia

    2010-01-01

    Background Enhanced and prolonged expression of connective tissue growth factor (CTGF) is associated with kidney fibrosis. Parathyroid hormone (PTH) is involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa in renal failure. PTH activated mitogen-activated protein kinase (MAPK) signaling pathway is present in renal tubular cells. The aim of this study was to identify the mechanism how the signal is transduced to result in extracellular signal-regulated protein kinase (ERK) activation, leading to upregulation of CTGF.Methods The levels of CTGF mRNA and protein in human kidney proximal tubular cells (HK-2) treated with PTH in the presence or absence of the MAPK inhibitor PD98059 were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and immunoblotting assay. The activation of the CTGF promoter in HK-2 cells was determined by the dual-luciferase assay. The effects of the protein kinase A (PKA) activator 8-Br-cAMP and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) on MAPK phosphorylation, and the effects of the PKA inhibitor H89 and PKC inhibitor calphostin C on MAPK phosphorylation and CTGF expression were detected by immunoblotting assay.Results PD98059 inhibited the PTH stimulated expression of CTGF, which strongly suggested that the MAPK signaling pathway plays an important role in the PTH-induced CTGF upregulation in renal tubular cells. A PKA activator as well as PKC activators induced MAPK phosphorylation, and both PKA and PKC inhibitors antagonized PTH-induced MAPK phosphorylation and CTGF expression.Conclusion CTGF expression is upregulated by PTH through a PKC/PKA-ERK-dependent pathway.

  17. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Directory of Open Access Journals (Sweden)

    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  18. Histopathological evaluation of surgically treated adult renal tumors: Report from a tertiary care center in India

    Directory of Open Access Journals (Sweden)

    B Datta

    2016-01-01

    Full Text Available Background: This retrospective study was performed in a tertiary care center from India analyzing the histopathological reports and the clinical data of the adult patients admitted in this institute with a diagnosis of renal tumors and had undergone nephrectomy for the disease. Objective: The objective of this study is to determine the relative frequencies of different renal tumors in adults (above the age of 16 years and to analyze the histopathological characters of the tumors. Materials and Methods: In this retrospective study, we have analyzed the histopathology reports along with the demographic and clinical data of the adult patients who had undergone nephrectomy for renal tumors in our institute from January 2005 to December 2011. Results: A total 113 adult patients underwent tumor nephrectomy during the last 7 years in our institute. Mean age of the patients was 54.5 years (range 16-69 years. Male:Female ratio was 1.9:1. Out of 131 cases of adult renal tumors, 91.6% cases were malignant and 8.45 cases were benign tumors. Among the malignant tumors, renal cell carcinoma was the most common type. There were 2 cases of renal primitive neuroectodermal tumors and one case of renal myofibroblastoma in our series. Conclusion: The spectrum of adult renal tumors in this series is consistent with the other series of cases reported by different authors. Only few cases of the renal tumors were diagnosed incidentally among our patients which is just opposite to the rate of renal tumors diagnosed incidentally in the developed countries. Myofibroblastoma, a benign kidney tumor diagnosed in our series is probably the first reported case in the world.

  19. SIRT1 activator ameliorates the renal tubular injury induced by hyperglycemia in vivo and in vitro via inhibiting apoptosis.

    Science.gov (United States)

    Wang, Xue-Ling; Wu, Li-Yan; Zhao, Long; Sun, Li-Na; Liu, Hai-Ying; Liu, Gang; Guan, Guang-Ju

    2016-10-01

    . These findings indicated that the increased expression of SIRT1, mediated by RSV, is a possible mechanism by which RSV prevents renal tubular injury in diabetic nephropathy (DN). So RSV has great clinical significance and could provide the basis for the new way to effective treatment to contain the morbidity and mortality associated with DN. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Kohei [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Fujiki, Katsunori; Shirahige, Katsuhiko [Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo (Japan); Gomez-Sanchez, Celso E. [Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS (United States); Endocrinology, University of Mississippi Medical Center, MS (United States); Fujita, Toshiro [Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Nangaku, Masaomi [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Nagase, Miki, E-mail: mnagase-tky@umin.ac.jp [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Department of Anatomy and Life Structure, School of Medicine Juntendo University, Tokyo (Japan)

    2014-02-28

    Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10{sup −7} M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10{sup −7} M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10{sup −9} M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

  1. MUTATIONS IN THE VHL GENE FRIOM POTASSIUM BROMATE-INDUCED RAT CLEAR CELL RENAL TUMORS

    Science.gov (United States)

    Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. ...

  2. Renal Tubular Acidosis

    Science.gov (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  3. Renal Tubular Acidosis

    Science.gov (United States)

    ... Looking for Health Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development ( ... may involve stopping use of the drug or changing the dosage. If an underlying disease or other ...

  4. Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.

    Science.gov (United States)

    Al-Qusairi, Lama; Basquin, Denis; Roy, Ankita; Stifanelli, Matteo; Rajaram, Renuga Devi; Debonneville, Anne; Nita, Izabela; Maillard, Marc; Loffing, Johannes; Subramanya, Arohan R; Staub, Olivier

    2016-08-01

    The stimulation of postprandial K(+) clearance involves aldosterone-independent and -dependent mechanisms. In this context, serum- and glucocorticoid-induced kinase (SGK)1, a ubiquitously expressed kinase, is one of the primary aldosterone-induced proteins in the aldosterone-sensitive distal nephron. Germline inactivation of SGK1 suggests that this kinase is fundamental for K(+) excretion under conditions of K(+) load, but the specific role of renal SGK1 remains elusive. To avoid compensatory mechanisms that may occur during nephrogenesis, we used inducible, nephron-specific Sgk1(Pax8/LC1) mice to assess the role of renal tubular SGK1 in K(+) regulation. Under a standard diet, these animals exhibited normal K(+) handling. When challenged by a high-K(+) diet, they developed severe hyperkalemia accompanied by a defect in K(+) excretion. Molecular analysis revealed reduced neural precursor cell expressed developmentally downregulated protein (NEDD)4-2 phosphorylation and total expression. γ-Epithelial Na(+) channel (ENaC) expression and α/γENaC proteolytic processing were also decreased in mutant mice. Moreover, with no lysine kinase (WNK)1, which displayed in control mice punctuate staining in the distal convoluted tubule and diffuse distribution in the connecting tubule/cortical colleting duct, was diffused in the distal convoluted tubule and less expressed in the connecting tubule/collecting duct of Sgk(Pax8/LC1) mice. Moreover, Ste20-related proline/alanine-rich kinase phosphorylation, and Na(+)-Cl(-) cotransporter phosphorylation/apical localization were reduced in mutant mice. Consistent with the altered WNK1 expression, increased renal outer medullary K(+) channel apical localization was observed. In conclusion, our data suggest that renal tubular SGK1 is important in the regulation of K(+) excretion via the control of NEDD4-2, WNK1, and ENaC.

  5. Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

    Science.gov (United States)

    Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

    2015-07-01

    The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine.

  6. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  7. Composite renal cell carcinoma with clear cell renal cell carcinomatous and carcinoid tumoral elements: a first case report.

    Science.gov (United States)

    Bressenot, A; Delaunay, C; Gauchotte, G; Oliver, A; Boudrant, G; Montagne, K

    2010-02-01

    Renal endocrine tumours are extremely rare, and carcinoid tumoral elements in renal cell carcinoma have never been reported. This is the first report of a composite renal cell carcinoma containing a clear cell renal cell carcinoma associated with carcinoid tumoral elements, in a patient with synchronous metastatic disease. In the absence of specific radiological and clinical manifestations, typical morphological features as well as an immunostaining profile of neuroendocrine differentiation were identified by microscopy. Secondary nodal and liver localisations were characterised by carcinoid elements only. Despite antiangiogenic therapy, liver metastasis progressed, suggesting that adjuvant therapy cannot be based on the presence of the clear cell renal cell carcinoma component. In this context, extensive tissue sampling is recommended to reveal the endocrine component that is the most aggressive element of such a composite carcinoma.

  8. 肌酐代谢产物对肾小管上皮细胞凋亡的影响%Effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    胡白瑛

    2013-01-01

    目的 研究肌酐产物是否能促进肾小管上皮细胞凋亡.方法 原代培养人肾小管上皮细胞,将肌酐产物与肾小管上皮细胞共同培养,对肾小管上皮细胞进行形态学观察;抽提DNA进行琼脂糖电泳观察有无梯形条带.结果 肾小管上皮细胞在肌酐产物作用下逐渐变小、变圆、固缩,最后漂浮死亡,但胞膜始终完整;肌酐产物导致肾小管上皮细胞凋亡,琼脂糖凝胶中有DNA梯形条带,加入谷胱甘肽(GSH)未见DNA梯形条带.结论 肌酐产物促进肾小管上皮细胞凋亡,GSH可阻断之.%Objective To study the effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells. Methods Renal tubular epithelia were cultured in vitro. The metabolites of creatinine and renal tubular epithelial cells were incubated together. The morphological change of renal tubular epithelial cells was observed. Gel electrophoresis of DNA extracted from that to observe bands of apoptotsis. Results Affected by metabolites of creatinine, renal tubular epithelial cells showed characters of apoptosis (smaller, round, pyknosis and death), but the cell membrane was always integral. Agarose gel electrophoresis revealed the appearance of DNA ladder, which disappeared with the addition of GSH. Conclusion The metabolites of creatinine can induce the apoptosis of renal tubular epithelial cells, which could be reversed by GSH.

  9. Cellular adaptive response of distal renal tubular cells to high-oxalate environment highlights surface alpha-enolase as the enhancer of calcium oxalate monohydrate crystal adhesion.

    Science.gov (United States)

    Kanlaya, Rattiyaporn; Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2013-03-27

    Hyperoxaluria is one of etiologic factors of calcium oxalate kidney stone disease. However, response of renal tubular cells to high-oxalate environment remained largely unknown. We applied a gel-based proteomics approach to characterize changes in cellular proteome of MDCK cells induced by 10mM sodium oxalate. A total of 14 proteins were detected as differentially expressed proteins. The oxalate-induced up-regulation of alpha-enolase in whole cell lysate was confirmed by 2-D Western blot analysis. Interaction network analysis revealed that cellular adaptive response under high-oxalate condition involved stress response, energy production, metabolism and transcriptional regulation. Down-regulation of RhoA, which was predicted to be associated with the identified proteins, was confirmed by immunoblotting. In addition, the up-regulation of alpha-enolase on apical surface of renal tubular epithelial cells was also confirmed by immunoblotting of the isolated apical membranes and immunofluorescence study. Interestingly, blockage of alpha-enolase expressed on the cell surface by antibody neutralization significantly reduced the number of calcium oxalate monohydrate (COM) crystals adhered on the cells. These results strongly suggest that surface alpha-enolase plays an important role as the enhancer of COM crystal binding. The increase of alpha-enolase expressed on the cell surface may aggravate kidney stone formation in patients with hyperoxaluria. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells.

    Science.gov (United States)

    Wang, Tao; He, Qian; Xiao, Liang; Wang, Qianqian; Zhang, Bo; Wang, Beilei; Liu, Guoyan; Zheng, Jiemin; Yu, Bentong; Zhang, Liming

    2013-11-01

    Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E cells. The results showed that TE caused cell morphological change and decreased cell viability through induction of apoptosis and necrosis in NRK-52E cells. Meanwhile, ROS overproduction and mitochondrial membrane potential decrease were found before the cell death occurred. It was concluded that TE could induce cytotoxicity, especially apoptosis and necrosis, in NRK-52E cells, and mitochondrial dysfunction and ROS overproduction might play important roles in the process of cell injury and death.

  11. Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury.

    Science.gov (United States)

    Jang, Hee-Seong; Han, Sang Jun; Kim, Jee In; Lee, Sanggyu; Lipschutz, Joshua H; Park, Kwon Moo

    2013-12-01

    Extracellular signal-regulated kinase (ERK) signals play important roles in cell death and survival. However, the role of ERK in the repair process after injury remains to be defined in the kidney. Here, we investigated the role of ERK in proliferation and differentiation of tubular epithelial cells, and proliferation of interstitial cells following ischemia/reperfusion (I/R) injury in the mouse kidney. Mice were subjected to 30min of renal ischemia. Some mice were administered with U0126, a specific upstream inhibitor of ERK, daily during the recovery phase, beginning at 1day after ischemia until sacrifice. I/R caused severe tubular cell damage and functional loss in the kidney. Nine days after ischemia, the kidney was restored functionally with a partial restoration of damaged tubules and expansion of fibrotic lesions. ERK was activated by I/R and the activated ERK was sustained for 9days. U0126 inhibited the proliferation, basolateral relocalization of Na,K-ATPase and lengthening of primary cilia in tubular epithelial cells, whereas it enhanced the proliferation of interstitial cells and accumulation of extracellular matrix. Furthermore, U0126 elevated the expression of cell cycle arrest-related proteins, p21 and phospholylated-chk2 in the post-ischemic kidney. U0126 mitigated the post-I/R increase of Sec10 which is a crucial component of exocyst complex and an important factor in ciliogenesis and tubulogenesis. U0126 also enhanced the expression of fibrosis-related proteins, TGF-β1 and phosphorylated NF-κB after ischemia. Our findings demonstrate that activation of ERK is required for both the restoration of damaged tubular epithelial cells and the inhibition of fibrosis progression following injury.

  12. Ossifying renal tumor of infancy: findings at ultrasound, CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hwan; Choi, Young Hun; Kim, Woo Sun; Cheon, Jung-Eun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, The Institute of Radiation Medicine, Seoul (Korea, Republic of); Moon, Kyung Chul [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of)

    2014-05-15

    A 4-month-old boy presented with persistent gross hematuria. At ultrasonography, a 3.5-cm echogenic mass with posterior shadowing and tumor vascularity was detected within the right renal pelvis. Precontrast CT showed a slightly hyperattenuating mass in the renal pelvis. At MRI the mass was heterogeneously hypointense on T2-weighted images and isointense on T1-weighted images. Contrast-enhanced CT and MRI both revealed peripheral enhancement of the mass. A histological diagnosis of ossifying renal tumor of infancy was made after open pyelostomy and tumor enucleation. We suggest that ossifying renal tumor of infancy should be considered when a mass with posterior acoustic shadowing and tumor vascularity on US, hyperattenuation on precontrast CT and hypointensity on T2-weighted MRI is seen within the renal pelvis of an infant with hematuria. (orig.)

  13. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer

    OpenAIRE

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-01-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormal...

  14. Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model.

    Science.gov (United States)

    Shrestha, Swojani; Somji, Seema; Sens, Donald A; Slusser-Nore, Andrea; Patel, Divyen H; Savage, Evan; Garrett, Scott H

    2017-09-15

    The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd(+2)), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features. Recently a new proximal tubule cell line was developed, the RPTEC/TERT1, and the goal of this study was to determine if this cell line could serve as a model to study nephrotoxicity. Global gene expression analysis of this cell line in comparison to the HK-2 and HPT cells showed that the RPTEC/TERT1 cells had gene expression patterns similar to HPT cells when compared to the HK-2 cells. The HPT and the RPTEC/TERT1 cell line had an increased population of stem/progenitor cells co-expressing CD24 and CD133 when compared to the HK-2 cells. The level of expression of cadherins, claudins and occludin molecules was also similar between the RPTEC/TERT1 and the HPT cells. Acute exposure to Cd(+2) resulted in necrosis of the RPTEC/TERT1 cells when compared to the HK-2 cells which died by apoptosis. Thus, the RPTEC/TERT1 cells are similar to HPT cells and can serve as a good model system to study mechanisms involved in toxicant induced renal damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping

    DEFF Research Database (Denmark)

    Juul, Troels; Palm, Fredrik; Nielsen, Per Mose;

    2016-01-01

    ) C MR is suitable for cells isolated from kidney tissue, without prior cell culture. METHODS: Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system...

  16. Identification of Tubular Heparan Sulfate as a Docking Platform for the Alternative Complement Component Properdin in Proteinuric Renal Disease

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Hakvoort, Jelleke J.; Navis, Gerjan J.; van Goor, Harry; Daha, Mohamed R.; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2011-01-01

    Properdin binds to proximal tubular epithelial cells (PTEC) and activates the complement system via the alternative pathway in vitro. Cellular ligands for properdin in the kidney have not yet been identified. Because properdin interacts with solid-phase heparin, we investigated whether heparan sulfa

  17. Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

    Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

  18. Bilateral synchronous occurrence of three different histological types of renal tumor: a case report

    Directory of Open Access Journals (Sweden)

    Radopoulos Demetrios

    2009-04-01

    Full Text Available Abstract Introduction Renal cell carcinomas account for 85% of all renal neoplasms. With the introduction of modern imaging modalities, there has been an increased diagnosis of renal tumors. Recent studies have shown that partial nephrectomy can be as safe as radical nephrectomy for smaller renal tumors. Renal cell carcinomas are usually unilateral, however, they can be bilateral in 2% to 4% of sporadic cases and considerably more common in familial cases. Case presentation In this case report, we describe an unusual case of two bilateral synchronous chromophobe renal cell carcinomas accompanied by an oncocytoma and an angiomyolipoma, that were all treated by open partial nephrectomy. Conclusions To the best of our knowledge, this is the first case report on the synchronous occurrence of bilateral chromophobe renal cell carcinomas associated with an oncocytoma and an angiomyolipoma.

  19. Intracellular delivery of the p38 mitogen-activated protein kinase inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in renal tubular cells : A novel strategy to treat renal fibrosis

    NARCIS (Netherlands)

    Prakash, Jai; Sandovici, Maria; Saluja, Vinay; Lacombe, Marie; Schaapveld, Roel Q. J.; de Borst, Martin H.; van Goor, Harry; Henning, Robert H.; Proost, Johannes H.; Moolenaar, Frits; Keri, Gyorgy; Meijer, Dirk K. F.; Poelstra, Klaas; Kok, Robbert J.

    2006-01-01

    During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the t

  20. Intracellular delivery of the p38 mitogen-activated protein kinase inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in renal tubular cells : A novel strategy to treat renal fibrosis

    NARCIS (Netherlands)

    Prakash, Jai; Sandovici, Maria; Saluja, Vinay; Lacombe, Marie; Schaapveld, Roel Q. J.; de Borst, Martin H.; van Goor, Harry; Henning, Robert H.; Proost, Johannes H.; Moolenaar, Frits; Keri, Gyorgy; Meijer, Dirk K. F.; Poelstra, Klaas; Kok, Robbert J.

    2006-01-01

    During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the

  1. Modification of Antitumor Immunity and Tumor Microenvironment by Resveratrol in Mouse Renal Tumor Model.

    Science.gov (United States)

    Chen, Liang; Yang, Sixing; Liao, Wenbiao; Xiong, Yunhe

    2015-06-01

    Renal cell carcinoma (RCC) microenvironment plays critical roles in antitumor immune response. Resveratrol exhibits a direct antitumor effect in various tumor models. However, the immunomodulatory effect of resveratrol on RCC microenvironment is unknown. In this study, we found that administration of low dose of resveratrol inhibits Renca tumor growth and its inhibition effect depends on CD8(+) T cells. Moreover, the proportion of regulatory T cells is decreased, while the proportion of myeloid-derived suppressor cells does not alter after resveratrol treatment. More importantly, massive amount of activated CD8(+) T cells accumulates in tumor microenvironment in the resveratrol-treated group and shows increased cytotoxicity, as indicated by a higher expression of Fas ligand. We also found that resveratrol switches the expression of T-helper (Th) 2 cytokines such as interleukin (IL)-6 and IL-10 to Th 1 cytokines with dominance of interferon (IFN)-γ, which increases the expression of Fas in Renca cells. Furthermore, we found resveratrol down-regulates angiogenesis along with decreased level of vascular endothelial growth factor in tumor microenvironment. Our results strongly suggest that resveratrol might be used for RCC immunotherapy through modulating tumor microenvironment.

  2. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

    Directory of Open Access Journals (Sweden)

    Rodriguez Macías EL

    2013-09-01

    Full Text Available Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen obstruction. Other mechanisms involved in renal injury are microangiopathy and pro-inflammatory mediators. We conclude that the nephrotoxicity caused by cisplatin can induce renal failure in which tubular structural damage predominates.

  3. Renal cell carcinoma with vena caval tumor thrombus extending into the right atrium

    Institute of Scientific and Technical Information of China (English)

    JIANG Hai; ZHANG Zhi-gen; CHEN Zhao-dian; SHI Shi-fang; CAI Song-liang; WANG Shuo

    2006-01-01

    @@ The incidence of the inferior vena cava (IVC)tumor thrombus is reported to be 4%-10% in patients with renal cell carcinoma (RCC). Tumor thrombus may extend through to the right atrium.Management of patients with level Ⅲ/Ⅳ tumor thrombus is usually difficult. We report two cases of level Ⅳ thrombus in our hospital in 2002 and 2004.

  4. Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients.

    Science.gov (United States)

    Kuthi, Levente; Jenei, Alex; Hajdu, Adrienn; Németh, István; Varga, Zoltán; Bajory, Zoltán; Pajor, László; Iványi, Béla

    2017-07-01

    The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a two-tiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the four-tiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.

  5. Leiomyosarcoma presenting as a spontaneously ruptured renal tumor-case report

    Directory of Open Access Journals (Sweden)

    Ather M

    2002-11-01

    Full Text Available Abstract Background Ruptured renal neoplasms can be a catastrophic clinical presentation. Angiomyolipoma is the commonest renal tumor which presents in this fashion. Renal sarcomas are rare renal neoplasms. Renal leiomyosarcomas are the most common histological subtype of renal sarcomas, accounting for approximately 50–60% of the reported cases. These tumors are usually peripherally located and appear to arise from either the renal capsule or smooth muscle tissue in the renal pelvic wall. Case presentation A 70 years old male, with hypertension and ischemic disease, developed acute left flank pain. The general physician evaluated this using ultrasound, which showed a solid left renal mass. Two weeks later, he presented in the emergency room in a state of shock with a palpable flank mass. CT scan of the abdomen showed a large heterogeneous mass lesion in the left perinephric space with minimal post contrast enhancement. Per-operatively, large retroperitoneal hematoma was found within Gerota's fascia along with spleen plastered to the upper limit of hematoma. Nephrectomy and splenectomy were performed. Postoperative course was uneventful and patient was discharged on the 10th post-operative day. Histopathological evaluation of the specimen showed high-grade leiomyosarcoma Conclusions Spontaneous rupture of renal neoplasm is a rare clinical presentation. Angiomyolipoma is the commonest cause of spontaneous rupture of the kidney. Presentation of a leimyosarcoma as a ruptured renal neoplasm has not been previously reported in the English literature.

  6. Massive hematuria due to a congenital renal arteriovenous malformation mimicking a renal pelvis tumor: a case report

    Directory of Open Access Journals (Sweden)

    Sountoulides P

    2008-05-01

    Full Text Available Abstract Introduction Congenital renal arteriovenous malformations (AVMs are very rare benign lesions. They are more common in women and rarely manifest in elderly people. In some cases they present with massive hematuria. Contemporary treatment consists of transcatheter selective arterial embolization which leads to resolution of the hematuria whilst preserving renal parenchyma. Case presentation A 72-year-old man, who was heavy smoker, presented with massive hematuria and flank pain. CT scan revealed a filling defect caused by a soft tissue mass in the renal pelvis, which initially led to the suspicion of a transitional cell carcinoma (TCC of the upper tract, in view of the patient's age and smoking habits. However a subsequent retrograde study could not depict any filling defect in the renal pelvis. Selective right renal arteriography confirmed the presence of a renal AVM by demonstrating abnormal arterial communication with a vein with early visualization of the venous system. At the same time successful selective transcatheter embolization of the lesion was performed. Conclusion This case highlights the importance of careful diagnostic work-up in the evaluation of upper tract hematuria. In the case presented, a congenital renal AVM proved to be the cause of massive upper tract hematuria and flank pain in spite of the initial evidence indicating the likely diagnosis of a renal pelvis tumor.

  7. Toxicological Significance of Renal Bcrp: Another Potential Transporter in the Elimination of Mercuric Ions from Proximal Tubular Cells

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.; Joshee, Lucy

    2015-01-01

    Secretion of inorganic mercury (Hg2+) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg2+ was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg2+. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg2+-induced nephropathy, Sprague-Dawley and Bcrp knockout (bcrp−/−) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol • kg−1), a moderately nephrotoxic (1.5 μmol • kg−1) or a significantly nephrotoxic (2.0 μmol • kg−1) dose of HgCl2. In general, the accumulation of Hg2+ was greater in organs of bcrp−/− rats than in Sprague-Dawley rats, suggesting that Bcrp may play a role in the export of Hg2+ from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp−/− rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. PMID:25868844

  8. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

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    Bridges, Christy C., E-mail: bridges_cc@mercer.edu; Zalups, Rudolfs K.; Joshee, Lucy

    2015-06-01

    Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

  9. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

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    Kristoffer Svensson

    Full Text Available The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.

  10. Laparoscopic partial nephrectomy for T1a renal tumors is safe and feasible

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; GAO Zhen-li; LIN Chun-hua; WU Ji-tao; WANG Lin; WANG Jian-ming; SUN De-kang; WANG Ke; YU Qing-xia

    2011-01-01

    Background Some patients with exophytic renal masses less than 4 cm and suboptimal renal function, or a solitary kidney and bilateral renal tumors are considered for laparoscopic partial nephrectomy (LPN), which is feasible for early-stage renal tumors, although it is still considered technically difficult and time consuming. Shortening the time of the operation and renal warm ischemia are required urgently. In this study, we report our initial experiences of LPN,especially with some improved surgical techniques. Methods Between July 2005 and October 2009, 74 patients with T1a renal tumor were treated by LPN, 39 using transperitoneal approach and 35 using retroperitoneal approach. In all cases, the tumor was removed with a margin of 0.5 cm. We compared glomerular filtration rate (GFR) preoperatively and postoperatively, and renal warm ischemia time between traditional ligature and Hem-o-lok methods. Results All operations were completed successfully, and there was no conversion to open surgery. Mean operation time was 76 minutes (range, 68-120), mean time of renal warm ischemia was 23 minutes (range, 15-32), and mean blood loss was 65 ml (range, 40-300). No hemorrhage or urine leak was observed in two cases with the collecting system sewn. Thirteen cases used Hem-o-lok to clamp the suture instead of traditional ligature, and mean time of renal warm ischemia was (16.5±2.3) minutes (range, 12-18). Mean postoperative hospital stay was 6.3 days (range, 5-12).Sixty-seven cases had renal clear cell carcinoma, six papillary renal cell carcinoma, and one renal collecting duct carcinoma. All the tumor margin specimens were negative. The mean follow-up was 30.6 months (range, 3-51), and no recurrence or metastasis was observed. Conclusions LPN for pT1 stage renal tumor was safe and feasible. Hem-o-lok instead of traditional ligature to clamp the suture when sewing the renal wound could shorten the warm ischemia time.

  11. Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice

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    Xin-Xin Pang

    2016-07-01

    Full Text Available Background/Aims: Urotensin II (UII and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN. The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress and Epithelial-mesenchymal transition (EMT in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1, fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

  12. [Tumor of upper urinary tract in renal polycystic disease].

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    Rabii, Redouane; el Mejjad, Amine; Fekak, Hamid; Querfani, Baderdine; Joual, Abdenbi; el Mrini, Mohamed

    2003-09-01

    Upper urinary tract tumours are exceptional in the context of renal polycystic disease. The authors report the case of Mrs B. F., 56 years old, who presented with left loin pain associated with haematuria. Clinical examination was normal and ultrasound examination revealed bilateral renal polycystic disease with a mass in the left renal sinus. CT urography showed a tumour arising from the renal pelvis suggestive of an upper urinary tract tumour. The laboratory assessment revealed normal renal function and normal urine cytology. Treatment consisted of radical nephroureterectomy with resection of a bladder cuff. Histological examination revealed a urothelial tumour of the renal pelvis with negative surgical margins. In the light of this case, the authors discuss the diagnostic difficulties and specificities, the treatment and the outcome of this unusual clinical association.

  13. Left adrenal tumor extending into the renal vein: surgical management with ipsilateral kidney preservation.

    Science.gov (United States)

    Doerfler, Arnaud; Vaudreuil, Lionel; Le Gal, Sophie; Lebreton, Gil; Tillou, Xavier

    2015-08-04

    If single adrenal metastasis surgery is well admitted, no recommendation exists about the management of a renal vein tumor thrombus, even though the actual consensual attitude consists in a nephrectomy associated to an adrenalectomy. We report, here, the case of a 74-year-old man with a suspected adrenal metastasis of a lung carcinoma associated with a left adrenal and renal vein tumor thrombus treated by adrenalectomy and renal vein thrombectomy and ipsilateral kidney sparing. The postoperative computed tomography scan showed no thrombus in the left renal vein. Doppler ultrasound performed 1 month after adrenalectomy proved a good left renal vein flux. At 36 months of follow-up, the patient is alive without signs of recurrence. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2015.

  14. Proximal tubular dysfunction is associated with chronic allograft nephropathy and decreased long-term renal-graft survival

    NARCIS (Netherlands)

    Camara, N.O.S.; Silva, M.S.; Nishida, S.; Pereira, A.B.; Pacheco-Silva, A.

    2004-01-01

    Background: Chronic allograft nephropathy is the major cause of graft loss after the first year of transplantation. Although many conditions are associated with its development, there is no method that can anticipate its risk in patients with good renal function. Methods: We prospectively studied 92

  15. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells.

    Science.gov (United States)

    Liang, Jie; Chen, Fuxue; Gu, Fu; Liu, Xin; Li, Feng; Du, Dongshu

    2017-04-01

    The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca(2+) intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca(2+) intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca(2+) concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

  16. [Conservative surgical treatment of renal carcinoma. Personal experience with 29 surgical excisions of tumors].

    Science.gov (United States)

    Villani, U; Pastorello, M

    1991-03-01

    From 1980 to 1988, elective conservative surgery (tumorectomy by enucleo-resection) was performed for renal cell carcinoma at stage I in 29 patients. An accurate preoperative renal investigation was carried out to identify the exact extension of the tumor and to study all the parenchimal situation, through IVP, ultrasound, CT scanning and, particularly, conventional selective angiography. The operative technique employed was: lymphadenectomy, peri-pararenal fat extirpation, in situ tumor enucleation by circular incision of the renal capsule and blunt dissection of the renal parenchyma with 2 cm safety margin to the tumor; multiple biopsies in the "bed" of resection for histopathologic peroperative evaluation; careful examination of the pseudocapsule and surrounding renal tissue; hemostasis. Follow-up was 10-113 months (mean 40,34 months). 2 of 29 patients died for progression of disease (at 52nd and 16yh month from surgery, 2/29 died for non-neoplastic reasons; 25/29 pts are living without local recurrences or distant metastases. In the same period (1980-1988), radical nephrectomy was performed for renal tumors at stage I in 34 patients. In an average observation period of 49,67 months, 2/34 patients died for progression of disease; 3/34 pts died for non-neoplastic reasons. 1/34 patient is living with pulmonar metastases and 28/34 are living without evidence of cancer. From this study we have got the conclusion that elective renal-sparing excision of the tumor (with macro-micro examination of the abscission surfaces) should be considered as a curative treatment in the case of low stage single tumors smaller than 7 cm, peripherally located in renal cortex, with unbroken pseudocapsule.

  17. Histopathological characterization of renal tubular and interstitial changes in 5/6 nephrectomized marmoset monkeys (Callithrix jacchus).

    Science.gov (United States)

    Suzuki, Yui; Yamaguchi, Itaru; Myojo, Kensuke; Kimoto, Naoya; Imaizumi, Minami; Takada, Chie; Sanada, Hiroko; Takaba, Katsumi; Yamate, Jyoji

    2015-01-01

    Common marmosets (Callithrix jacchus) have become a useful animal model, particularly for development of biopharmaceuticals. While various renal failure models have been established in rodents, there is currently no acceptable model in marmosets. We analyzed the damaged renal tubules and tubulointerstitial changes (inflammation and fibrosis) of 5/6 nephrectomized (Nx) common marmosets by histopathological/immunohistochemical methods, and compared these findings to those in 5/6 Nx SD rats. In Nx marmosets and rats sacrificed at 5 and 13 weeks after Nx, variously dilated and atrophied renal tubules were seen in the cortex in common; however, the epithelial proliferating activity was much less in Nx marmosets. Furthermore, the degrees of inflammation and fibrosis seen in the affected cortex were more severe and massive in Nx marmosets with time-dependent increase. Interestingly, inflammation in Nx marmosets, of which degree was less in Nx rats, consisted of a large number of CD3-positive T cells and CD20-positive B cells (occasionally forming follicles), and a few CD68-positive macrophages. Based on these findings, lymphocytes might contribute to the progressive renal lesions in Nx marmosets. Fibrotic areas in Nx marmosets comprised myofibroblasts expressing vimentin and α-smooth muscle actin (α-SMA), whereas along with vimentin and α-SMA expressions, desmin was expressed in myofibroblasts in Nx rats. This study shows that there are some differences in renal lesions induced by Nx between marmosets and rats, which would provide useful, base-line information for pharmacology and toxicology studies using Nx marmosets.

  18. Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.

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    Prabhat Bastola

    Full Text Available Von Hippel-Lindau tumor suppressor (VHL is lost in the majority of clear cell renal cell carcinomas (ccRCC. Folliculin (FLCN is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD, a disorder characterized by renal cancer of multiple histological types including clear cell carcinoma, cutaneous fibrofolliculoma, and pneumothorax. Here we explored whether there is connection between VHL and FLCN in clear cell renal carcinoma cell lines and tumors. We demonstrate that VHL regulates expression of FLCN at the mRNA and protein levels in RCC cell lines, and that FLCN protein expression is decreased in human ccRCC tumors with VHL loss, as compared with matched normal kidney tissue. Knockdown of FLCN results in increased formation of tumors by RCC cells with wild-type VHL in orthotopic xenografts in nude mice, an indication that FLCN plays a role in the tumor-suppressing activity of VHL. Interestingly, FLCN, similarly to VHL, is necessary for the activity of LC3C-mediated autophagic program that we have previously characterized as contributing to the tumor suppressing activity of VHL. The results show the existence of functional crosstalk between two major tumor suppressors in renal cancer, VHL and FLCN, converging on regulation of autophagy.

  19. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    Science.gov (United States)

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  20. Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.

    Science.gov (United States)

    Buijs, Nikki; Vermeulen, Mechteld A R; Weeda, Viola B; Bading, James R; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2015-01-01

    Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

  1. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

    Science.gov (United States)

    Kornhauser, Carlos; Dubey, Luis-Antonio; Garay, M-Eugenia; Pérez-Luque, Elva-Leticia; Malacara, Juan-Manuel; Vargas-Origel, Arturo

    2002-05-01

    Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

  2. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

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    Sabiha S. Chowdhury

    2016-08-01

    Full Text Available Along with diabetes and obesity, chronic kidney disease (CKD is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

  3. Matrilysin (MMP-7) Inhibition of BMP-7 Induced Renal Tubular Branching Morphogenesis Suggests a Role in the Pathogenesis of Human Renal Dysplasia

    Science.gov (United States)

    Harju-Baker, Susanna; Rims, Cliff; Sheen, Joong-Hyuk; Liapis, Helen

    2012-01-01

    Congenital renal dysplasia (RD) is a severe form of congenital renal malformation characterized by disruption of normal renal development with cyst formation, reduced or absent nephrons, and impaired renal growth. The authors previously identified that matrilysin (matrix metalloproteinase–7) was overexpressed in a microarray gene expression analysis of human RD compared to normal control kidneys. They now find that active matrilysin gene transcription and protein synthesis occur within dysplastic tubules and epithelial cells lining cysts in human RD by RT-PCR and immunohistochemistry. Similar staining patterns were seen in obstructed kidneys of pouch opossums that show histological features similar to that of human RD. In vitro, matrilysin inhibits formation of branching structures in mIMCD-3 cells stimulated by bone morphogenetic protein–7 (BMP-7) but does not inhibit hepatocyte growth factor–stimulated branching. BMP-7 signaling is essential for normal kidney development, and overexpression of catalytically active matrilysin in human embryonic kidney 293 cells reduces endogenous BMP-7 protein levels and inhibits phosphorylation of BMP-7 SMAD signaling intermediates. These findings suggest that matrilysin expression in RD may be an injury response that disrupts normal nephrogenesis by impairing BMP-7 signaling. PMID:22215634

  4. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

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    Sandy Azzi

    2015-06-01

    Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

  5. Mitochondrial Fission Increases Apoptosis and Decreases Autophagy in Renal Proximal Tubular Epithelial Cells Treated with High Glucose.

    Science.gov (United States)

    Lee, Wen-Chin; Chiu, Chien-Hua; Chen, Jin-Bor; Chen, Chiu-Hua; Chang, Hsueh-Wei

    2016-11-01

    The aim of this study was to examine the effect of mitochondrial morphogenesis changes on apoptosis and autophagy of high-glucose-treated proximal tubular epithelial cells (HK2). Cell viability, apoptosis, and mitochondrial morphogenesis were examined using crystal violet, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and mitotracker staining, respectively. High glucose inhibited cell viability and induced mitochondrial fission in HK2 cells. After depleting mitofusin 1 (MFN1), the MFN1(-) HK2 cells (fission type) became more susceptible to high-glucose-induced apoptosis and mitochondrial fragmentation observed by TUNEL and mitotracker assays. In siMFN2 HK2 cells (fission type), mitochondria were highly fragmented (>80% fission rate) with or without high-glucose treatment; however, siFIS1 (mitochondrial fission protein 1) HK2 cells (fusion type) exhibited little fragmentation (High-glucose treatment induced autophagy, characterized by the formation of autophagosome and microtubule-associated protein light chain 3 (LC3) B-II, as observed by transmission electron microscopy and western blotting, respectively. LC3B-II levels decreased in both MFN1(-) and siMFN2 HK2 cells, but increased in siFIS1 HK2 cells. Moreover, autophagy displays a protective role against high-glucose-induced cell death based on cotreatment with autophagy inhibitors (3-methyladenine and chloroquine). Mitochondrial fission may increase apoptosis and decrease autophagy of high-glucose-treated HK2 cells.

  6. Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families

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    Mohammad Al-Haggar

    2011-01-01

    Full Text Available Background. Fanconi-Bickel syndrome (FBS is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2 gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA were deleted (c.253 254delGA and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A. Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

  7. Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families.

    Science.gov (United States)

    Al-Haggar, Mohammad; Sakamoto, Osamu; Shaltout, Ali; El-Hawary, Amany; Wahba, Yahya; Abdel-Hadi, Dina

    2011-01-01

    Background. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA) were deleted (c.253 254delGA) and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A). Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

  8. THE ADVISABILITY AND SAFETY OF TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY FOR RENAL PARENCHYMAL TUMORS

    Directory of Open Access Journals (Sweden)

    V. B. Matvee

    2014-01-01

    Full Text Available Objective: to assess the advisability and safety of transperitoneal laparoscopic nephrectomy for renal parenchymal tumors.Subjects and methods. The investigation enrolled 163 patents with clinically localized renal parenchymal tumors that had been resected through laparoscopic (n = 81 (49.7 % and open (n = 82 (50.3 % accesses. The groups of patients operated on via laparoscopic and laparotomic accesses were matched for demographic characteristics, somatic status, baseline renal function, and nephrometric signs of tumor nodules, except the involved side (7 patients in the laparoscopic group had bilateral renal tumors. Renal resection was carried out in all the patients; a contralateral kidney tumor was also removed in 7 patients with a bilateral lesion (nephrectomy and kidney resection were done in 3 and 4 patients, respectively. Histological examination verified benign tumors in 15 (9.2 % cases, renal cell carcinoma in 148 (90.8 %, including all bilateral renal tumors [рТ1а (n = 135 (91.2 % cases; рТ1b (n = 4 (2.7 %; рТ3а (n = 9 (6.1 %]; according to the pT category, the distribution of patients in the laparoscopic and open resection groups was even (p = 0.586. No additional treatment was performed in any case. The median follow-up was 48.2 ± 11.8 months.Results. The use of the laparoscopic access significantly increased the frequency of intraoperative complications (6.1 and 16.0 %; p = 0.037, but failed to affect that of postoperative complications (13.0 and 18.3 %, respectively; p = 0.291 versus the open access. Laparoscopic versus conventional techniques did not cause any reduction in 5-year overall, specific, and relapse-free survival rates (93.3, 100.0, 80.0 % and 97.1, 100.0, 98.5 %, respectively; р > 0.05 for all. The rate of acute renal dysfunction and its distribution by the RIFLE classes, the rate and level of a decrease in glomerular filtration rate in the late postoperative period did not depend on the surgical access (p

  9. THE ADVISABILITY AND SAFETY OF TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY FOR RENAL PARENCHYMAL TUMORS

    Directory of Open Access Journals (Sweden)

    V. B. Matvee

    2014-07-01

    Full Text Available Objective: to assess the advisability and safety of transperitoneal laparoscopic nephrectomy for renal parenchymal tumors.Subjects and methods. The investigation enrolled 163 patents with clinically localized renal parenchymal tumors that had been resected through laparoscopic (n = 81 (49.7 % and open (n = 82 (50.3 % accesses. The groups of patients operated on via laparoscopic and laparotomic accesses were matched for demographic characteristics, somatic status, baseline renal function, and nephrometric signs of tumor nodules, except the involved side (7 patients in the laparoscopic group had bilateral renal tumors. Renal resection was carried out in all the patients; a contralateral kidney tumor was also removed in 7 patients with a bilateral lesion (nephrectomy and kidney resection were done in 3 and 4 patients, respectively. Histological examination verified benign tumors in 15 (9.2 % cases, renal cell carcinoma in 148 (90.8 %, including all bilateral renal tumors [рТ1а (n = 135 (91.2 % cases; рТ1b (n = 4 (2.7 %; рТ3а (n = 9 (6.1 %]; according to the pT category, the distribution of patients in the laparoscopic and open resection groups was even (p = 0.586. No additional treatment was performed in any case. The median follow-up was 48.2 ± 11.8 months.Results. The use of the laparoscopic access significantly increased the frequency of intraoperative complications (6.1 and 16.0 %; p = 0.037, but failed to affect that of postoperative complications (13.0 and 18.3 %, respectively; p = 0.291 versus the open access. Laparoscopic versus conventional techniques did not cause any reduction in 5-year overall, specific, and relapse-free survival rates (93.3, 100.0, 80.0 % and 97.1, 100.0, 98.5 %, respectively; р > 0.05 for all. The rate of acute renal dysfunction and its distribution by the RIFLE classes, the rate and level of a decrease in glomerular filtration rate in the late postoperative period did not depend on the surgical access (p

  10. Prostatic adenocarcinoma (PCa metastasizing to renal cell carcinoma (RCC with periureteral tumor deposit: A case of tumor-to-tumor metastasis (TTM

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    Jenissa Amor Dionisio Arceño, MD

    2017-06-01

    Full Text Available Renal cell carcinoma (RCC and prostatic adenocarcinoma (PCa, occurring as a double primary is uncommon, but well documented. However, metastatic PCa in a RCC is quite rare. We report a case of an 81-year old male chemical engineer with history of hematuria and prostatomegaly suspicious for carcinoma, who underwent left radical nephrectomy for a renal mass. Histopathology revealed RCC that harbored an undiagnosed PCa. Periureteral tumor deposit likewise showed combined metastasis of RCC and PCa.

  11. Role of tumor-associated macrophages in renal cell carcinoma pathogenesis

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    O. V. Kovaleva

    2017-01-01

    Full Text Available The role of tumor stroma in malignant tumor pathogenesis cannot be disputed. Macrophages are one of the crucial elements of tumor stroma. Tumor-associated macrophages (TAMs are type 2-activated macrophages (M2. They were first described in 1992. They carry CD206, CD163, FXIIIa, βIG-H3, stabilin 1, YKL-39, SI-CLP, tenascin С, LOX-1, fibronectin, MARCO, interleukin 1 receptor antagonist (IL-1RA and other markers. Unlike proinflammatory macrophages (M1, М2 display high anti-inflammatory activity and are responsible for inflammation reaction suppression and tissue recovery in inflamed area. TAMs significantly contribute to tumor progression by stimulating cell proliferation, angiogenesis, and suppression of antitumor immune response. Identification of macrophages in renal tumors involves a limited number of markers, which doesn’t allow making a conclusive answer about their function. However, a correlation between TAMs content and a negative disease prognosis can be considered proven. Studies of M1 and M2 using different markers have shown that renal tumors contain high levels of TAMs with mixed M1/M2 phenotype. TAMs in renal tumors are highly proangiogenic and immunosuppressive. TAMs density can be used as a prognostic marker, but development of an effective treatment strategy aimed at inhibition of TAMs antitumor activity requires systemic research involving a wide panel of M1 and M2 macrophage markers. 

  12. Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis.

    Science.gov (United States)

    Mul, D; Grote, F K; Goudriaan, J R; de Muinck Keizer-Schrama, S M P F; Wit, J M; Oostdijk, W

    2010-01-01

    Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a -2.0 SDS cutoff for weight and body mass index, respectively. In infants and toddlers diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in older children. In short children >3 years RTA was extremely rare, always associated with clinical symptoms, and rarely detected by blood gas analysis. According to our data a decreasing weight SDS for age is a sufficient indication to perform blood gas analysis in children 3 years of age. Copyright © 2010 S. Karger AG, Basel.

  13. Overexpression of angiotensinogen downregulates aquaporin 1 expression via modulation of Nrf2–HO-1 pathway in renal proximal tubular cells of transgenic mice

    Directory of Open Access Journals (Sweden)

    Shiao-Ying Chang

    2016-09-01

    Full Text Available Introduction: We aimed to examine the regulation of aquaporin 1 expression in an angiotensinogen transgenic mouse model, focusing on underlying mechanisms. Methods: Male transgenic mice overexpressing rat angiotensinogen in their renal proximal tubular cells (RPTCs and rat immortalised RPTCs stably transfected with rat angiotensinogen cDNA were used. Results: Angiotensinogen-transgenic mice developed hypertension and nephropathy, changes that were either partially or completely attenuated by treatment with losartan or dual renin–angiotensin system blockade (losartan and perindopril, respectively, while hydralazine prevented hypertension but not nephropathy. Decreased expression of aquaporin 1 and heme oxygenase-1 and increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and sodium–hydrogen exchanger 3 were observed in RPTCs of angiotensinogen-transgenic mice and in angiotensinogen-transfected immortalised RPTCs. These parameters were normalised by dual renin–angiotensin system blockade. Both in vivo and in vitro studies identified a novel mechanism in which angiotensinogen overexpression in RPTCs enhances the cytosolic accumulation of Nrf2 via the phosphorylation of pGSK3β Y216. Consequently, lower intranuclear Nrf2 levels are less efficient to trigger heme oxygenase-1 expression as a defence mechanism, which subsequently diminishes aquaporin 1 expression in RPTCs. Conclusions: Angiotensinogen-mediated downregulation of aquaporin 1 and Nrf2 signalling may play an important role in intrarenal renin–angiotensin system-induced hypertension and kidney injury.

  14. Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer.

    Science.gov (United States)

    Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina

    2016-12-01

    Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormalities arising in the setting of known renal cell carcinoma, particularly late in the course of disease. This is frequently associated with internal jugular vein thrombi, which should be evaluated with an abnormal thyroid. Thyroglobulin levels are usually normal in such patients.

  15. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

    Science.gov (United States)

    Ueda, Kohei; Fujiki, Katsunori; Shirahige, Katsuhiko; Gomez-Sanchez, Celso E.; Fujita, Toshiro; Nangaku, Masaomi; Nagase, Miki

    2017-01-01

    Background and objective Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10−7 M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7 M aldosterone for 3 h by microarray. Results 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9 M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases. PMID:24491541

  16. Preventing acute renal failure is crucial during acute tumor lysis syndrome

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    Darmon Michael

    2007-01-01

    Full Text Available Tumour Lysis syndrome (TLS is characterized by the massive destruction of tumoral cells and the release in the extracellular space of their content. While TLS may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms and cause hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Moreover, TLS may lead to an acute renal failure (ARF. In addition to the hospital mortality induced by the acute renal failure itself, development of an ARF may preclude optimal cancer treatment. Therefore, prevention of the acute renal failure during acute tumor lysis syndrome is mandatory. The objective of this review is to describe pathophysiological mechanisms leading to acute tumor lysis syndrome, clinical and biological consequences of this syndrome and to provide up-to-date guidelines to ensure prevention and prompt management of this syndrome.

  17. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

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    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  18. Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

    OpenAIRE

    Brenner, Walburgis; Färber, Gloria; Jan G. Hengstler; Herget, Thomas; Thüroff, Joachim W.; Wiesner, Christoph

    2003-01-01

    Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was ex...

  19. Efecto citotóxico de la toxina shiga tipo 2 y su subunidad b en células epiteliales tubulares renales humanas en cultivo Cytotoxic effect of Shiga toxin type 2 and its B subunit on human renal tubular epithelial cell cultures

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    Virginia Pistone Creydt

    2005-04-01

    Full Text Available Escherichia coli enterohemorrágica productora de toxina Shiga (Stx causa diarrea acuosa, colitis hemorrágica y síndrome urémico hemolítico (SUH. En Argentina, el SUH es la principal causa de insuficiencia renal en niños. El objetivo de este trabajo fue estudiar la toxicidad de Stx tipo 2 (Stx2 y su subunidad B (Stx2B en células epiteliales tubulares renales humanas (CERH, en presencia y ausencia de factores inflamatorios. Los efectos citotóxicos se evaluaron como alteración de la funcionalidad del epitelio; daños histológicos; viabilidad celular; síntesis de proteínas y apoptosis celular. Los resultados muestran que Stx2 regula el pasaje de agua a través de CERH a tiempos menores de 1h de incubación. A tiempos mayores, hasta 72 hs, el estudio de la morfología, la viabilidad, la síntesis de proteínas y la apoptosis demostró que las CERH fueron sensibles a la acción citotóxica de Stx2 y Stx2B de una manera dosis y tiempo dependiente. Estos efectos fueron potenciados por lipopolisacáridos bacterianos (LPS, IL-1b, y butirato.Shiga toxin (Stx-producing E.coli causing watery diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome (HUS. In Argentina, HUS is the most common cause of acute renal failure in children. The purpose of the present study was to examine the cytotoxicity of Stx type 2 (Stx2 and its B subunit (Stx2B on human renal tubular epithelial cells (HRTEC, in the presence and absence of inflammatory factors. Cytotoxic effects were assessed in terms of functionality of the epithelium, histological damage, cell viability, protein synthesis and cellular apoptosis. Results show that Stx2 regulates the passage of water through the HRTEC within an incubation period of 1h. Within longer periods, up to 72 hours, the study of morphology, viability, protein synthesis and apoptosis shows that HRTEC were sensitive to the cytotoxic action of Stx2 and Stx2B in a dose- and time-dependent manner. These effects were potentiated by

  20. Morphometric scores for renal tumors: What does the radiologist need to know?

    Energy Technology Data Exchange (ETDEWEB)

    Millet, Ingrid; Doyon, Fernanda Curros; Pages, Emma [Department of Imaging, CHU Montpellier (France); Thuret, Rodolphe [Department of Urology, CHU Montpellier (France); Taourel, Patrice, E-mail: p-taourel@chu-montpellier.fr [Department of Imaging, CHU Montpellier (France)

    2014-08-15

    Numerous therapeutic options are possible in the treatment of renal carcinomas including radical nephrectomy, partial nephrectomy, cryoablation, radiofrequency, active follow-up and among surgical treatments, different approaches may be used such as laparotomy, laparoscopy, robotic-assisted intervention. The choice between these different procedures is partially based on the anatomic conditions of the tumors. Different anatomic scores determined from cross-sectional imaging have been built to predict the complexity of the surgical procedure. The goals of this article are to review the relevant morphologic pattern for management of patients with renal tumors, to know how to calculate these different scores and to understand the clinical applications of these scores.

  1. Diagnostic Value of Processing Cytologic Aspirates of Renal Tumors in Agar Cell (Tissue) Blocks

    DEFF Research Database (Denmark)

    Smedts, F.; Schrik, M.; Horn, T.;

    2010-01-01

    Objective To adapt a method enabling utilization of most of the harvest from a fine needle aspirate in an effort to improve diagnostic accuracy in the assessment of a renal tumor in a single histologic slide. Study Design In a series of 43 renal tumors, 2 fine needle aspirations were performed, 4...... smears were prepared after each aspiration for conventional cytology and the remaining aspirate was processed for the improved agar microbiopsy (AM) method. Conventional cytology slides, AM slides and surgical specimens were diagnosed separately, after which the diagnoses were compared...

  2. Brown tumor: clinical findings of secondary hyperparathyroidism in patients with renal osteodystrophy.

    Science.gov (United States)

    Silva, Mairaira Teles Leão E; Cedraz, Juliana Silva Barros; Pontes, Caetano Guilherme Carvalho; Trento, Cleverson Luciano; Brasileiro, Bernardo Ferreira; Piva, Marta Rabello; Pereira, Fabiano Alvim

    2017-01-01

    A brown tumor, or osteoclastoma, is a nonneoplastic bony lesion associated with hyperparathyroidism and directly related to increased levels of parathyroid hormone. These tumors result from excessive osteoclastic activity. This article presents 3 cases of brown tumor localized in facial bones. The lesions were the result of secondary hyperparathyroidism associated with chronic renal failure. The patients were two 42-year-old men and a 39-year-old woman. All patients had been treated systemically by hemodialysis for more than 10 years. This article highlights the importance of proper diagnosis and management of dental patients presenting with a brown tumor.

  3. Unusual Renal Tumors — Report of Four Cases

    African Journals Online (AJOL)

    A 56 years old male patient presented with history of pain in his right lumbar ... His renal and liver function tests were also normal. Serum cal- .... M protein concentration, if present (9). ... Soft tissue plasmacytoma can be classified into 3 clinical.

  4. The Effect of Tumor Histopathology on Renal Function After Radical Nephrectomy

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    Eymen Gazel

    2016-01-01

    Full Text Available Aim: Patients with renal cell carcinoma (RCC have increase risk for chronic kidney disease (CKD. In our study, it was aimed to find the relationship between tumor related histopathologic properties and post-op renal functions of patients who underwent radical nephrectomy due to renal tumor. Material and Method: The data of 130 patients, who underwent radical nephrectomy, was retrospectively examined.The patient groups were classified among themselves as those with a post-operative e-GFR of below (group1 and above(group2 60mL/min/1.73m² and those with a post-operative e-GFR of or below (groupA and above(groupB 30mL/min/1.73m². Results: In terms of tumoral properties of Group A and Group B, there was not a statistically significant difference between tumor types (p=0,263, tumor T stages (p=1,0, Fuhrman grades (p=0,12, capsular invasions (p=1,0, renal vein invasions (p=1,0, lymph node involvements (p=1,0, distant metastases presences (p=0,639 of two groups. In terms of tumoral properties of Group 1 and Group 2, there was not a statistically significant difference between tumor types (p=0,283, tumor T stages (p=0,096, Fuhrman grades (p=0,27, capsular invasions (p=0,345, renal vein invasions (p=0,183, lymph node involvements (p=0,718, distant metastases presences (p=1,0 of two groups. Discussion: There is need for comprehensive studies in order to find whether tumor histopathology is one of the parameters that affect renal functions after radical nephrectomy.It should be remembered that knowing the parameters that affect renal function of this patient group, which has an already increased CKD risk, will allow us to follow them up more closely and this will directly affect the survival of patients

  5. Radiological classification of renal angiomyolipomas based on 127 tumors

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    Prando Adilson

    2003-01-01

    Full Text Available PURPOSE: Demonstrate radiological findings of 127 angiomyolipomas (AMLs and propose a classification based on the radiological evidence of fat. MATERIALS AND METHODS: The imaging findings of 85 consecutive patients with AMLs: isolated (n = 73, multiple without tuberous sclerosis (TS (n = 4 and multiple with TS (n = 8, were retrospectively reviewed. Eighteen AMLs (14% presented with hemorrhage. All patients were submitted to a dedicated helical CT or magnetic resonance studies. All hemorrhagic and non-hemorrhagic lesions were grouped together since our objective was to analyze the presence of detectable fat. Out of 85 patients, 53 were monitored and 32 were treated surgically due to large perirenal component (n = 13, hemorrhage (n = 11 and impossibility of an adequate preoperative characterization (n = 8. There was not a case of renal cell carcinoma (RCC with fat component in this group of patients. RESULTS: Based on the presence and amount of detectable fat within the lesion, AMLs were classified in 4 distinct radiological patterns: Pattern-I, predominantly fatty (usually less than 2 cm in diameter and intrarenal: 54%; Pattern-II, partially fatty (intrarenal or exophytic: 29%; Pattern-III, minimally fatty (most exophytic and perirenal: 11%; and Pattern-IV, without fat (most exophytic and perirenal: 6%. CONCLUSIONS: This proposed classification might be useful to understand the imaging manifestations of AMLs, their differential diagnosis and determine when further radiological evaluation would be necessary. Small (< 1.5 cm, pattern-I AMLs tend to be intra-renal, homogeneous and predominantly fatty. As they grow they tend to be partially or completely exophytic and heterogeneous (patterns II and III. The rare pattern-IV AMLs, however, can be small or large, intra-renal or exophytic but are always homogeneous and hyperdense mass. Since no renal cell carcinoma was found in our series, from an evidence-based practice, all renal mass with detectable

  6. Tumor antigens and markers in renal cell carcinoma.

    NARCIS (Netherlands)

    Mulders, P.F.A.; Bleumer, I.; Oosterwijk, E.

    2003-01-01

    Tumor markers are mainly used to diagnose specific malignancies. The methods commonly involve immunohistochemistry and cytogenetics, including FISH and RT-PCR. In RCC, the investigated tumor markers (summarized in Table 1) show additional prognostic value over classical prognostic factors such as st

  7. Tumor antigens and markers in renal cell carcinoma.

    NARCIS (Netherlands)

    Mulders, P.F.A.; Bleumer, I.; Oosterwijk, E.

    2003-01-01

    Tumor markers are mainly used to diagnose specific malignancies. The methods commonly involve immunohistochemistry and cytogenetics, including FISH and RT-PCR. In RCC, the investigated tumor markers (summarized in Table 1) show additional prognostic value over classical prognostic factors such as

  8. Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors

    Directory of Open Access Journals (Sweden)

    Oliveira Jorge

    2007-07-01

    Full Text Available Abstract Background Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors. Methods A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC, 13 papillary (pRCC, 10 chromophobe (chRCC, and 10 oncocytomas and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters. Results Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007, PTGS2 (p = 0.002, and RASSF1A (p = 0.0001. CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively, whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004. RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035. In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031 and nuclear grade (p = 0.022, respectively. Conclusion The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

  9. Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

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    Yonneau Laurent

    2010-12-01

    Full Text Available Abstract Background Germline mutations in the folliculin (FLCN gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS, a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. Methods BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. Results Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. Conclusions Our results support a genetic distinction between BHDS-associated tumors and other renal

  10. What meralgia paresthetica can hide: renal tumor as an infrequent cause.

    Science.gov (United States)

    Ramírez Huaranga, Marco Aurelio; Ariza Hernández, Andrés; Ramos Rodríguez, Claudia Carolina; González García, Jesús

    2013-01-01

    Meralgia paresthetica is a mononeuropathy of the femoral cutaneous nerve with characteristic findings, usually secondary to injury or compression, being most common in the inguinal area. Exceptional cases associated with compressions caused by abdominal or pelvic tumors have been published, so it is always advisable to extend the study with imaging tests. We present a case associated with a renal tumor. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  11. Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience.

    Science.gov (United States)

    Alguersuari, A; Mateos, A; Falcó, J; Criado, E; Fortuño, J R; Guitart, J

    2016-01-01

    To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. RFA is efficacious and safe, with results comparable to those reported in the literature. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. 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)

  13. Rare Renal Incidentaloma in Pregnancy: An Unusual Primitive Neuroectodermal Tumor Presentation

    OpenAIRE

    2015-01-01

    Peripheral Primitive Neuroectodermal Tumors (PNETs) are rare lesions that arise from outside the central nervous system and normally do not affect the genitourinary system. Primary renal presentations are extremely rare but given their aggressive behavior and characteristic cytomorphologic and genetic features should be considered well-defined distinct clinical entities in order to distinguish them from other primary tumors featuring round cells in the kidney. We report one case of PNET invol...

  14. Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

    Science.gov (United States)

    Kuroda, N; Furuya, M; Nagashima, Y; Gotohda, H; Kawakami, F; Moritani, S; Ota, S; Hora, M; Michal, M; Hes, O; Nakatani, Y

    2014-06-01

    Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

  15. Photothermal Ablation of in Situ Renal Tumor by PEG-IR780-C13 Micelles and Near-Infrared Irradiation.

    Science.gov (United States)

    Qiu, Xuefeng; Xu, Linfeng; Zhang, Yanting; Yuan, Ahu; Wang, Kaikai; Zhao, Xiaozhi; Wu, Jinhui; Guo, Hongqian; Hu, Yiqiao

    2016-03-07

    PEG-IR780-C13 micelles have been demonstrated to be a novel photothermal agent with tumor-targeting property. This study was designed to explore the feasibility of applying PEG-IR780-C13 micelles and near-infrared (NIR) irradiation for thermal ablation of renal tumor by using an in situ tumor model. In addition, the potential thermal injury to normal renal tissue was evaluated. PEG-IR780-C13 micelles were intended to accumulate in renal tumor after systemic delivery. In vitro results revealed that PEG-IR780-C13 micelles were uptaken by RENCA cells mainly through caveola-mediated endocytosis and mainly distributed in late endosomes and lysosomes. Upon NIR irradiation, PEG-IR780-C13 micelles generated heat effectively both in vitro and in vivo, exhibiting a promising photothermal therapeutic property. The photothermal effect of PEG-IR780-C13 micelles could effectively destroy RENCA cells in vitro and adequately inhibit growth of in situ renal tumor in vivo. Meanwhile, PEG-IR780-C13 micelles mediated photothermal therapy (PTT) resulting in only limited injury to normal renal tissue surrounding tumor sites. Our data indicated that PEG-IR780-C13 micelles mediating PTT could generate tumor-specific heat for destruction of renal tumor in a minimally invasive way, providing a novel strategy for thermal ablation of renal tumor.

  16. Multifocal Renal Cell Carcinoma: Clinicopathologic Features and Outcomes for Tumors ≤4 cm

    Directory of Open Access Journals (Sweden)

    Paul L. Crispen

    2008-01-01

    Full Text Available A significant increase in the incidental detection of small renal tumors has been observed with the routine use of cross-sectional abdominal imaging. However, the proportion of small renal tumors associated with multifocal RCC has yet to be established. Here then, we report our experience with the treatment of multifocal RCC in which the primary tumor was ≤4 cm. In our series of 1113 RCC patients, 5.4% (60/1113 had multifocal disease at the time of nephrectomy. Discordant histology was present in 17% (10/60 of patients with multifocal RCC. Nephron sparing surgery was utilized more frequently in patients with solitary tumors. Overall, cancer-specific, and distant metastasis-free survival appeared to be similar between multifocal and solitary tumors. These findings are consistent with previous series which evaluated multifocal RCC with tumors >4 cm. With the known incidence of multifocality RCC, careful inspection of the entire renal unit should be performed when performing nephron sparing surgery.

  17. MR imaging of renal cell carcinoma: associations among signal intensity, tumor enhancement, and pathologic findings.

    Directory of Open Access Journals (Sweden)

    Yabuki T

    2003-08-01

    Full Text Available The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation.

  18. Tumoral calcinosis in a dog with chronic renal failure : clinical communication

    Directory of Open Access Journals (Sweden)

    T.C. Spotswood

    2003-06-01

    Full Text Available A 2-year-old male German shepherd dog in poor bodily condition was evaluated for thoracic limb lameness due to a large, firm mass medial to the left cranial scapula. Radiography revealed several large cauliflower-like mineralized masses in the craniomedial left scapula musculature, pectoral region and bilaterally in the biceps tendon sheaths. Urinalysis, haematology and serum biochemistry showed that the dog was severely anaemic, hyperphosphataemic and in chronic renal failure. The dog was euthanased and a full post mortem performed. A diagnosis of chronic renal failure with secondary hyperparathyroidism was confirmed. The mineralized masses were grossly and histopathologically consistent with a diagnosis of tumoral calcinosis. Tumoral calcinosis associated with chronic renal failure that does not involve the foot pads is rarely seen.

  19. HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells

    NARCIS (Netherlands)

    Nishizawa, Satoshi; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Takahashi, Akari; Tamura, Yasuaki; Mori, Takashi; Kanaseki, Takayuki; Kamiguchi, Kenjiro; Asanuma, Hiroko; Morita, Rena; Sokolovskaya, Alice; Matsuzaki, Junichi; Yamada, Ren; Fujii, Reona; Kampinga, Harm H.; Kondo, Toru; Hasegawa, Tadashi; Hara, Isao; Sato, Noriyuki

    2012-01-01

    Cancer stem-like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB

  20. Brown tumors in patients with chronic renal failure and secondary hyperparathyroidism: Report of 12 cases

    Directory of Open Access Journals (Sweden)

    Fatma Lilia

    2010-01-01

    Full Text Available Brown tumors are unusual but serious complications of renal osteodystrophy. We retrospectively studied 12 patients presenting with chronic renal failure and brown tumor related to secondary hyperparathyroidism. Eleven patients were on chronic hemodialysis. The median duration between renal failure and end stage renal failure was 36 months (range: 12-190 months and the median duration in dialysis for 11 cases: 92 months (range: 72-252 months. The bone pain was noted in all cases (100%, pathological fracture in one case (8% and a palpable bone tumor in 10 cases (83%. Elevated serum Calcium (> 2.35 mmol/L was noted in four cases (33%, elevated serum Phosphate (> 1.78 mmol/L in ten cases (80%, elevated serum Alkaline Phosphate (> 290 UI/L in all cases and intact PTH was > 300 pg/mL in all cases with a serum median rate at 1475 pg/mL (range: 682-3687 pg/L. Subtotal parathyroidectomy was performed in all cases with a resultant decrease in size of brown tumors. We report here patient with CKD with unusual frequency and variable locations. This may be attributed tothe lack of the new calcium free phosphate binders and calcimimetics.

  1. Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

    Directory of Open Access Journals (Sweden)

    Hideyuki Iwayama

    2011-10-01

    Full Text Available Background/Aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs and whether it regulates cyclosporine A (CyA-induced apoptosis in renal proximal tubular cells (RPTCs. Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence and apoptosis (determined by Hoechst 33258 staining was examined in HK-2 cells. Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1–6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.

  2. The use of immunohistochemical expression of SF-1 and EMA in distinguishing adrenocortical tumors from renal neoplasms.

    Science.gov (United States)

    Enriquez, Miriam L; Lal, Priti; Ziober, Amy; Wang, Liping; Tomaszewski, John E; Bing, Zhanyong

    2012-03-01

    Steroidogenic factor -1 (SF-1) is an orphan member of the nuclear hormone receptor superfamily, and is considered to play an important role in the differentiation of steroidogenic tissues. In this study, we compared the immunohistochemical stains of SF-1 and epithelial membrane antigen (EMA) in non-neoplastic adrenal tissue, and adrenal and renal tumors using tissue microarrays (TMAs). The adrenal tissue array included 19 cases of normal adrenal cortex, 22 cases of adrenal adenoma, and 20 cases of adrenal cortical carcinoma. The renal tissue array included 20 cases of each of the following types of renal cell carcinoma: clear cell, papillary, and chromophobe. In addition, 20 cases of renal oncocytoma were also included in the study. SF-1 showed positive staining in all cases (100%) of normal adrenal cortex and adrenal cortical adenoma, and in 18 (90%) cases of adrenocortical carcinoma. In renal tumors, SF-1 showed negative stains in all of oncocytoma, papillary, and chromophobe renal cell carcinoma. Only 3 out of 20 cases of clear cell renal cell carcinoma showed weak positivity in approximately 10% of tumor cells. EMA stained positively in 85%, 95%, 100%, and 95% of clear cell, papillary, chromophobe renal cell carcinomas, and oncocytomas, respectively. EMA was completely negative in the adrenal TMAs. In conclusion, SF-1 and EMA may be helpful in the differentiation of adrenal tumors from renal tumors in difficult cases.

  3. Radiofrequency Ablation of Renal Tumors: Four-Year Follow-Up Results in 47 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soo Dong; Yoon, Seong Guk; Sung, Gyung Tak [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2012-09-15

    To retrospectively evaluate the intermediate results of radiofrequency ablation (RFA) of small renal masses (SRMs). Percutaneous or laparoscopic RFA was performed on 48 renal tumors in 47 patients. The follow-up studies included a physical examination, chest radiography, creatinine level, and contrast-enhanced CT or MRI. To confirm the pathologic criteria of complete ablation, 35 patients underwent a follow-up biopsy. Recurrence was defined as contrast enhancement on imaging studies after 3 months, lesion growth at subsequent imaging, or viable cancer cells on follow-up biopsy. Technical success was achieved in 43 (89.6%) of 48 renal tumors. The mean tumor size was 2.3 cm and the mean follow-up period was 49.6 months. Repeated RFA was necessary in 5 tumors due to incomplete ablation. The overall complication rate was 35.8%, of which 96.2% were mild complications. Serum creatinine levels at 12 months after RFA did not differ from those before RFA (1.28 vs. 1.36 mg/dL). Four patients were found to have recurrence at various follow-up intervals, and distant metastasis was not found in any cases. RFA appears to be a useful treatment for selected patients with SRMs. Our 4-year follow-up results disclose an excellent therapeutic outcome with RFA, while achieving effective local tumor control.

  4. Advances of MicroRNAs in Translational Medicine and Immunotherapy of Renal Tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin-en

    2016-01-01

    microRNA (miRNA) is an important molecular component for cells under normal and pathological status, and plays an important role in oncobiology, including the improvement of tumor growth, invasion, angiogenesis and immunoescape by inhibiting the expression of gene miRNAs. Translational medicine can accelerate the industrialization process of transforming scientific research into engineering application, and its application in medicine may lead to the fast shortening of distance between basic research and clinical practice. According to the study of miRNAs in translational medicine, it is discovered that the pathological subtypes of relative diseases can be identiifed and patients’ survival time and prognosis can be predicted through the expression proifles of miRNAs in tumors. The invasive examinations can be reduced to realize the diagnosis of tumors by detecting tumor-associated miRNA biomarkers, and miRNAs can be used for clinical treatment of tumors. Renal cell carcinoma (RCC) is a common tumor in urinary system, and application of some specific miRNAs as a biomarker for the complementary diagnosis and treatment as well as evaluation of prognosis has become a hot topic in modern medicine. This study mainly analyzed and summarized the latest development in miRNAs and tumor studies, hoping to provide a theoretical basis for the diagnosis and prognosis of renal cancer.

  5. Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers.

    Science.gov (United States)

    Chopra, Sameer; Liu, Jie; Alemozaffar, Mehrdad; Nichols, Peter W; Aron, Manju; Weisenberger, Daniel J; Collings, Clayton K; Syan, Sumeet; Hu, Brian; Desai, Mihir; Aron, Monish; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning; Siegmund, Kimberly D

    2017-01-17

    The clinical management of small renal masses (SRMs) is challenging since the current methods for distinguishing between benign masses and malignant renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false negative rates increase the risk of cancer progression and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures. We built a predictive classification model for kidney tumors using 697 DNA methylation profiles from six different subgroups: clear cell, papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal kidney tissues. Furthermore, the DNA methylation-dependent classifier has been validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs). In general, the results were highly reproducible (89%, n=70) in predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent-normals (n=102) were correctly classified as normal, while 92% of tumors (n=71) were correctly classified malignant and 86% of benign (n=29) were correctly classified benign by this classification model. Overall, this study provides molecular-based support for using routine needle biopsies to determine tumor classification of SRMs and support the clinical decision-making.

  6. Spontaneous renal tumors in two rats from a thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran resistant (DP-ØØ4114-3) maize.

    Science.gov (United States)

    Hardisty, Jerry F; Banas, Deborah A; Gopinath, Chirukandath; Hall, William C; Hard, Gordon C; Takahashi, Michihito

    2013-03-01

    A thirteen week feeding study was conducted by feeding young adult male and female Sprague Dawley [Crl:CD®(SD)] rats diets containing grain from genetically modified (GM) DP-ØØ4114-3 maize that was either untreated (4114) or treated in the field with glufosinate ammonium (4114GLU). Control rats were fed diets containing the same concentration of near isogenic, non-GM maize grain (091) or one of three types of commercially available non-GM maize grain. At the end of the in-life phase, renal tubule tumors were reported in two male rats consuming diets containing 4114 maize grain. An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded kidney histology sections from control (091) and treated (4114 and 4114GLU) male rats. The objectives were for the panel to characterize the histopathologic findings and to interpret their relationship to consumption of the indicated diet. The PWG concluded unanimously that the kidney tumors were characteristic of amphophilic-vacuolar (AV) tumors and AV atypical tubular hyperplasia which represent a distinctive phenotype that has been reported to occur sporadically in young Sprague Dawley Rats. The PWG determined that the neoplasms and atypical tubular hyperplasias were multicentric and bilateral which typifies tumors of familial origin. Degenerative/regenerative or cytotoxic changes consistent with nephrotoxicity leading to tumor induction were not observed in these rats and thus supports the conclusion that tumors were unrelated to consumption of the test diet. It was the unanimous opinion of the PWG that the proliferative renal tubule cell lesions were spontaneous and not related to consumption of diets containing 4114 maize grain.

  7. Comparison of renal function following donor nephrectomy versus radical nephrectomy for renal tumor

    Directory of Open Access Journals (Sweden)

    Mohamed Etafy

    2015-01-01

    Full Text Available In this study, we compared renal function in patients after donor nephrectomy (DN and radical nephrectomy (RN. We retrospectively reviewed 68 patients (mean follow-up 15 months, including 30 patients who had undergone DN and 38 patients who had undergone RN. The study was performed between April 2006 and July 2010 at a single institute. Patients were matched for age and co-morbidities (hypertension and diabetes mellitus. We calculated the estimated glomerular filtration rate (eGFR using the Modification of Diet in Renal Disease study group equation. Parameters studied included GFR (≥60 to 2.0 mg/dL, metabolic acidosis (serum bicarbonate 30 mg. There were no significant demographic differences between the two study groups. After a mean follow-up of 15 months, low eGFR (<60 mL/min/1.73 m 2 was seen in 28% and 6.7% of patients in the RN and DN groups, respectively (P = 0.03. Similarly, proteinuria was seen in 21% vs 0%, P = 0.007, and de novo elevated creatinine was seen in 13% vs 0%, respectively P = 0.04; thus the changes were greater in the RN group. Our study shows that undergoing RN had a significantly greater risk of developing renal insufficiency and proteinuria compared with age-and co-morbidity-matched patients undergoing DN. We concluded that patients undergoing RN show a significantly greater risk of developing renal insufficiency and proteinuria compared with the patients undergoing DN.

  8. Robotic nephron-sparing surgery for renal tumors: Current status.

    Science.gov (United States)

    Azhar, Raed A; Gill, Inderbir S; Aron, Monish

    2014-07-01

    There have been a number of advances in robotic partial nephrectomy (RPN) for renal masses. We reviewed these advances with emphasis on the evolution of technique and outcomes as well as the expanding indications for RPN. Literature in the English language was reviewed using the National Library of Medicine database. Relevant articles were extracted, and their citations were utilized to broaden our search. The identified articles were reviewed and summarized with a focus on novel developments. RPN is an evolving procedure and is an emerging viable alternative to laparoscopic partial nephrectomy and open partial nephrectomy with favorable outcomes. The contemporary techniques used for RPN demonstrate excellent perioperative outcomes. The short-term oncologic outcomes are comparable to those of laparoscopic and open surgical approaches. Further studies are needed to assess long-term oncologic control.

  9. Histotype differentiation of hypo-echoic renal tumors on CEUS: usefulness of enhancement homogeneity and intensity.

    Science.gov (United States)

    Lu, Qing; Xue, Li-yun; Huang, Bei-jian; Wang, Wen-ping; Li, Cui-xian

    2015-08-01

    The purpose of this study is to evaluate qualitative and quantitative analysis of contrast-enhanced ultrasound (CEUS) in differential diagnoses of hypo-echoic renal tumor histotypes. Our study cohort comprised 103 clear cell renal cell carcinomas (ccRCCs), 24 papillary renal cell carcinomas (pRCCs), 28 chromophobe renal cell carcinomas (cRCCs), and 34 angiomyolipomas (AMLs), hypo-echoic on ultrasound, and imaged between January 2011 and December 2013. Enhancement homogeneity and tumor-to-cortex intensity ratio (TOC ratio) were retrospectively analyzed. Overall, heterogeneous enhancement was more common in ccRCCs than AMLs, pRCCs, and cRCCs. TOC ratio showed the trend ccRCC > AML > pRCC = cRCC. Similar trends were seen in tumors 107.5% to differentiate ccRCC from other histotypes, the sensitivity, specificity, positive and negative predictive values were 93.1%, 74.5%, 84.8%, and 87.5%, respectively. Tumors >4 cm exhibited considerable overlap in enhancement homogeneity among different histotypes. TOC ratios were similar between homo- and heterogeneously enhancing tumors for ccRCCs and for pRCCs and cRCCs, but higher in homogeneously enhancing than heterogeneously enhancing AMLs. In homo- and heterogeneously enhancing tumors, TOC ratios followed the trends ccRCCs > AMLs > pRCCs = cRCCs and ccRCCs > AMLs = pRCCs = cRCCs, respectively. With TOC ratio >105.81% and >72.37% to differentiate homo- and heterogeneously enhancing ccRCCs from other histotypes in tumors >4 cm with same enhancement homogeneity, the sensitivity, specificity, positive and negative predictive values were 70.0%, 85.7%, 70.0%, 85.7%, and 91.7%, 94.4%, 95.7%, 89.5%, respectively. CEUS homogeneity and TOC ratio are helpful in differential diagnosis of hypo-echoic renal tumor histotypes. Diameter and enhancement homogeneity should be considered when deciding the diagnostic TOC ratio cutoff.

  10. Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

    2014-06-01

    In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

  11. Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea); Lee, Hyun Moo [Sungkyunkwan University School of Medicine, Department of Urology, Samsung Medical Center, Seoul (Korea)

    2008-07-15

    The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 {+-} 0.6 cm before ablation to 1.7 {+-} 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size. (orig.)

  12. Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Meloni, Maria Franca, E-mail: meloni.mariafranca@gmail.com [Department of Radiology, Ospedale Valduce, Como (Italy); Smolock, Amanda [Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Cantisani, Vito; Bezzi, Mario; D' Ambrosio, Ferdinando [Department of Radiology, Oncology and Anatomo-Pathology “Sapienza” University of Rome, Rome (Italy); Proiti, Maria [Department of Internal Medicine, Vittorio-Emanuele University Hospital, Catania (Italy); Lee, Fred [Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Aiani, Luca [Department of Radiology, Ospedale Valduce, Como (Italy); Calliada, Fabrizio [Department of Radiology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia (Italy); Ferraioli, Giovanna [Ultrasound Unit, Infectious Diseases Department, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia (Italy)

    2015-09-15

    Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors.

  13. Renal mucinous tubular and spindle cell carcinoma: two cases report and review of the literature%肾黏液性小管状和梭形细胞癌2例报道并文献复习

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Wei; Zhengyu Zhang; Jingping Ge; Jianping Gao; Wenquan Zhou

    2012-01-01

    We reported the clinical and pathologic features of two different types of renal mucinous tubular and spindle cell. carcinoma (MTSCC). The first patient was incidentally discovered by health examination, with lower nuclear grade, no part and distant metastasis. The second patient presented with persistence hyperpyrexia, part and distant metastasis, and high nuclear grade. Surgery were both performed successfully. The first patient had no recurrences and no distant metastases. The second patient died of multiple organ failure 3 months postoperatively. Although MTSCC is usually a low potential malignancy carcinoma, high malignancy may occur and lead to a fatal course. So it needs a proper management and prognostication.

  14. Mini-flank supra-12th rib incision for open partial nephrectomy for renal tumor with RENAL nephrometry score ≥10: an innovation of traditional open surgery.

    Science.gov (United States)

    Wang, Hang; Sun, Li-an; Wang, Yiwei; Xiang, Zhuoyi; Zhou, Lin; Guo, Jianming; Wang, Guomin

    2015-04-01

    The skill of supra-12th rib mini-flank approach for open partial nephrectomy (MI-OPN) provides an advanced operative method for renal tumor. Compared with laparoscopic and robotic surgery, it may be a feasible selection for the complex renal tumors. We describe our techniques and results of MI-OPN in complex renal tumors with high RENAL nephrometry score (RENAL nephrometry score ≥10). Fifty-five patients diagnosed with renal tumors between January 2009 and July 2013 were included in this study. Eligibility criteria comprised of patients with complex renal tumor (RENAL score ≥10) being candidates for partial nephrectomy (PN). All patients received MI-OPN and all surgeries were performed by a single urologist. The preoperative workup comprised of medical history, physical examination, and routine laboratory tests. Serum creatinine was recorded preoperatively and 2 to 3 months after operation. Operative time, ischemia time, blood loss, operative and postoperative complications, renal function, and pathology parameters were recorded. MI-OPN was successfully performed in all cases. Mean tumor size was 4.7 cm (range: 2.5-8.1). Mean warm ischemia time was 28.1 minutes (range: 21-39), mean operative time was 105 minutes (range: 70-150) and mean estimated blood loss was 68 mL (range: 10-400). Mean postoperative hospital stay was 6.5 days (range: 5-12). Postoperative complications were found in 3 patients (5.5%). The mean pre- and postoperative serum creatinine levels were 76.2 μmol/L (range: 47-132) and 87.1 μmol/L (range: 61-189) with significant difference (P = 0.004). The mean pre- and postoperative estimated glomerular filtration rate (eGFR) were 91.5 (range: 34-133) and 82.5 (range: 22-126.5), respectively with significant difference (P = 0.024). In an average follow-up of 19.9 months (range: 8-50), no local recurrence or systemic progression occurred. In conclusion, MI-OPN can combine the benefits of both minimal invasive and traditional open

  15. Efficiency and Reliability of Laparoscopic Partial Nephrectomy for Renal Tumors Larger than 4 cm

    Directory of Open Access Journals (Sweden)

    Faruk Özgör

    2015-03-01

    Full Text Available Aim: To evaluate safety and efficiency of laparoscopic partial nephrectomy for renal tumors larger than 4 cm. Methods: We retrospectivelly evaluated the medical records of 65 patients who underwent laparascopic partial nephrectomy between May 2009 and June 2013 in our clinic. The patients were divided into two groups according to tumor size. Patients with a tumor 4 cm were included in group 1 (n=45 and group 2 (n=20, respectively. Demographic, perioperative and postoperative parameters were compared between the groups. Histopathological examination and surgical margin status were also evaluated. Results: The mean age of the patients was 59.2±10.9 (range: 26- 81 years. The mean tumor size and the mean RENAL nephrometry score were significantly higher in group 2 than in group 1. The mean operation time and warm ischemia time were similar between groups but estimated blood loss and transfusion requirement were significantly higher in group 2. Convertion to open surgery was seen two patients in group 2 and one patient in group 1. Only one patient underwent radical nephrectomy for uncontrolled bleeding in group 2. There was no difference in preoperative and 3-month postoperative serum creatinine levels between the groups. The incidence of positive surgical margin was 0% and 5% in group 1 and group 2, respectively. Conclusion: Laparoscopic partial nephrectomy for renal tumors is an effective and feasible procedure with acceptable oncologic results. However, tranfusion rate and requiremet of pelvicaliceal system repair were more common in patients with tumor >4 cm. (The Medical Bulletin of Haseki 2015; 53:30-5

  16. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

    OpenAIRE

    Rodriguez Macías EL

    2013-01-01

    Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen...

  17. Sunitinib Does Not Accelerate Tumor Growth in Patients with Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Krastan B. Blagoev

    2013-02-01

    Full Text Available Preclinical studies have suggested that sunitinib accelerates metastases in animals, ascribing this to inhibition of the vascular endothelial growth factor receptor or the tumor’s adaptation. To address whether sunitinib accelerates tumors in humans, we analyzed data from the pivotal randomized phase III trial comparing sunitinib and interferon alfa in patients with metastatic renal cell carcinoma. The evidence clearly shows that sunitinib was not harmful, did not accelerate tumor growth, and did not shorten survival. Specifically, neither longer sunitinib treatment nor a greater effect of sunitinib on tumors reduced survival. Sunitinib did reduce the tumor’s growth rate while administered, thereby improving survival, without appearing to alter tumor biology after discontinuation. Concerns arising from animal models do not apply to patients receiving sunitinib and likely will not apply to similar agents.

  18. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient's individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations...... therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  19. A case of a desmoid tumor with an uretertumoral fisttula detected on renal scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun Woo; Lee, Kyu Taek; Lee, Sang Mi [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2016-11-15

    Desmoid tumors are rare benign tumors with aggressive fibroblastic proliferation. Although desmoid tumors do not metastasize, they have locally aggressive features and can cause a urinary fistula. Here, we report a case of a 35-year-old woman with Gardner syndrome who was diagnosed with an intra-abdominal desmoid tumor 1 year previously and who presented with a newly developed cystic mass lesion on a computed tomography scan. The cystic mass lesion was clinically diagnosed as an urinoma from the right ureterotumoral fistula; thus, surgical resection of the mass lesion was planned. However, Tc-99m diethylenetriamine pentaacetic acid renal scintigraphy revealed bilateral ureterotumoral fistulas; hence, the treatment plan was changed to conservative management.

  20. A Survey of Mesenchyme-related Tumors of the Rat Kidney in the National Toxicology Program Archives, with Particular Reference to Renal Mesenchymal Tumor.

    Science.gov (United States)

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J

    2016-08-01

    In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165 cases of mesenchyme-related tumors and nephroblastomas of the rat kidney were reexamined from the National Toxicology Program (NTP) Archives. This survey demonstrated that renal mesenchymal tumor (RMT) was the most common spontaneous nonepithelial tumor in the rat kidney, also occurring more frequently in the NTP studies than nephroblastoma. Renal sarcoma was a distinct but very rare tumor entity, representing a malignant, monomorphous population of densely crowded, fibroblast-like cells, in which, unlike RMT, preexisting tubules did not persist. Nephroblastoma was characterized by early death of affected animals, suggesting an embryonal origin for this tumor type. Male and female rats were equally disposed to developing RMT, but most of the cases of nephroblastoma occurred in female rats and liposarcoma occurred mostly in male rats. This survey confirmed discrete histopathological and biological differences between the mesenchyme-related renal tumor types and between RMT and nephroblastoma. Statistical analysis also demonstrated a lack of any relationship of these renal tumor types to test article administration in the NTP data bank.

  1. RENAL TUMOR QUANTIFICATION AND CLASSIFICATION IN TRIPLE-PHASE CONTRAST-ENHANCED ABDOMINAL CT

    Science.gov (United States)

    Gautam, Rabindra; Peterson, James; Yao, Jianhua; Linehan, W. Marston; Summers, Ronald M.

    2009-01-01

    It is estimated that a quarter of a million people in the USA are living with kidney cancer. In clinical practice, the response to treatment is monitored by manual measurements of tumor size, which are time consuming and show high intra- and inter-operator variability. We propose a computer-assisted radiology tool to assess renal tumors in contrast-enhanced CT for the management of tumor diagnoses and treatments. The algorithm employs anisotropic diffusion, a combination of fast-marching and geodesic level-sets, and a novel statistical refinement step to adapt to the shape of the lesions. It also quantifies the 3D size, volume and enhancement of the lesion and allows serial management of tumors. The comparison between manual and semi-automated quantifications shows disparity within the limits of inter-observer variability. The automated tumor classification shows great separation between cysts, von Hippel-Lindau syndrome (VHL) lesions and hereditary papillary renal carcinomas (HPRC) (p < 0.004). PMID:20383290

  2. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

    Directory of Open Access Journals (Sweden)

    Rowland Randall G

    2008-04-01

    Full Text Available Abstract Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy.

  3. 丹参注射液对梗阻性肾病梗阻解除后肾间质纤维化的影响%Salvia miltiorrhiza injection treatment on renal tubular interstitial fibrosis of obstructive nephropathy

    Institute of Scientific and Technical Information of China (English)

    王昭辉; 白遵光; 杨海峰

    2012-01-01

    目的:研究丹参注射液对梗阻性肾病梗阻解除后肾间质纤维化的影响.方法:将22只新西兰兔随机分为假手术组、造模组和丹参组,假手术组予术后普通喂养,造模组在解除梗阻后给予生理盐水腹腔注射,丹参组在解除梗阻后给予丹参注射液腹腔注射,观察三组的基本情况、血清学指标及肾间质病变情况.结果:丹参组血清肌酐(Cr)、尿素氮(Bun)含量较对照组低,P<0.05;丹参组病理标本中上皮细胞病变减轻,炎症细胞浸润较对照组少,间质增生减少,间质面积较对照组减少,P<0.05.结论:丹参注射液可以改善梗阻性肾病梗阻解除后肾间质纤维化情况,促进肾功能的恢复.%Aim:To explore the affect of Salvia miltiorrhiza injection treatment on renal tubular interstitial fibrosis. Methods: New Zealand rabbits were randomly divided into fake operational group control group and Salvia miltiorrhiza group, Salvia miltiorrhiza group was given Salvia miltiorrhiza injection by in-traperitoneal route after relief of obstruction lately 2 weeks, compared three groups of serological markers and renal tubular interstitial fibrosis. Results; The Blood creatinine levels and Blood urea nitrogen levels in Salvia miltiorrhiza group is lower than those of the control group(P <0. 05) ,the renal tubular interstitial level of Salvia miltiorrhiza group lower than control group ( P <0. 05 ). Conclusion: Salvia miltiorrhiza injection can improve renal tubulointerstitial fibrosis in obstructive nephropathy obstruction, promote recovery of renal function.

  4. A rare case of retroperitoneal malignant triton tumor invading renal vein and small intestine

    Directory of Open Access Journals (Sweden)

    Mijović Žaklina

    2013-01-01

    Full Text Available Introduction. Malignant Triton tumor is a very rare malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation. Most of those tumors occur in patients with von Recklinghausen’s disease or as a late complication of irradiation and commonly seen in the head, neck, extremities and trunk. Case report. We reported retroperitoneal malignant Triton tumor in a 57-year-old female patient. Skin lesions were not present, and there was no family history of neurofibromatosis or previous irradiation. The presented case is one of a few recorded in the specialized literature that occurs in the retroperitoneal space in sporadic form. In this case, tumor consisted of a multilobular mass was in close relation with the abdominal aorta and inferior vena cava and involved the renal vein with gross invasion of the small intestine. The patient underwent total resection of the tumor and left nefrectomy was performed. The small intestine 10 cm in length was also resected and end-to-end anastomosis was conducted. The postoperative course was uneventful and the patient was discharged from the hospital ten days after the surgery. Conclusion. Diagnostically, it is crucial to recognize this uncommon histological variant because malignant Triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does. The use of the immunohistochemistry is essential in making the correct diagnosis. Only appropriate pathological evaluation supported by immunostaining with S-100 protein and desmin confirmed the diagnosis. Aggressive surgical management treatment improves the prognosis of such cases with adjuvant radiotherapy.

  5. 肾小管性酸中毒骨骼并发症的临床分析%Clinical analysis of bone complications in renal tubular acidosis

    Institute of Scientific and Technical Information of China (English)

    马毓华; 谢静远; 张春丽; 李晓; 沈平雁; 任红; 陈楠

    2013-01-01

    Objectives This study aims to investigate the features of bone complications secondary to renal tubular acidosis(RTA) and to further discuss the differences and characteristics of clinical manifestations between patients with primary RTA (PRTA) or RTA Secondary to Sj? gren's syndrome (SRTA) patients.Methods We retrospectively recruited 109 SRTA patients and 144 PRTA patients who admitted to our clinical center during 1996 and 2010.Baseline demographic,clinical features,laboratory examinations,outcomes and isotope bone density examination were collected and analyzed.Results The study included 144 PRTA and 109 SRTA patients.In PRTA group,there were 63 men and 81 women,the average age was 38 years; In SRTA group,there were 10 men and 99 women,the average age was 42 years..Within the PRTA group,bone pain and joint pain occured in 22 cases (15.3%),reduced bone mass was observed in 3 cases (2.1%),osteoporosis was found in 17 cases (11.8%).While in SRTA group,25 patients (22.9%) were reported to have bone pain and joint pain,and reduced bone mass was found in 10 cases (9.2%),9 cases (8.3%) of the patients had osteoporosis.Accordingly,more patients with bone disease were detected in SRTA group than in PRTA group (37.6% vs 24.3%,p < 0.05).The isotope bone density with lumbar spine T value of 9 PRTA patients is more than the SRTA patients.Additionally,SRTA patients had a lower lumber spine T value than PRTA patients (-0.53 ± 0.97 vs-1.65 ± 1.29,P < 0.05) by isotope bone density test which indicated a higher frequency and more severe bone disease occurred in RTA patients with Sj? gren 's syndrome than primary RTA patients.Conclusions Sjgren's syndrome is the most common cause of secondary RTA,the incidence and severity of bone disease was higher in RTA patients secondary to Sj? gren's syndrome than primary RTA patients,which aroused early diagnosis and clinical attentions.%目的 总结肾小管酸中毒(Renal Tubular Acidosis,RTA)骨骼并发症的特

  6. Review Study of Renal Tubular Injury Markers in the Acute Kidney Injury%急性肾损伤中肾小管损伤标志物的研究进展

    Institute of Scientific and Technical Information of China (English)

    李一飞; 姚广涛

    2011-01-01

    The reports concerned with renal injury markers in recent 10 years were consulted through Science Direct database, and literature related to specific markers of renal tubular injury were compiled and analyzed. Some biomarkers have been partially verified the good sensitivity and high specificity in experimental studies and clinical observations. For example, Kidney injury molecule-1 .which would over express in the kidney injury in renal tubular epithelial cells,is sensitive to the early diagnosis of kidney cancer, ischemic and renal toxic renal injury,and detected with high stability. Liver-type fatty acid binding protein involved in local lipid metabolism of renal,with high specificity to renal proximal tubule. Its content in urine were of great value for early evaluation of various types of acute kidney injury. As a diagnostic indicator,sensitivity and specificity of Interleukin-18 were more than 90%. It could distinguish acute tubular necrosis from other types of kidney diseases, also predict the renal injury occurrence and renal function recovery. Neutrophil gelatinase-associated lipocalin was often detected as the first expressed product in the injury kidney,which changed earlier than creatinine and other markers, with obvious time advantage. All biomarkers have different characteristics and respective shortage. So joint detection were better to wider and sensitive evaluation of renal injury.%通过Science Direct数据库查阅了近10年有关肾损伤标志物的报道,对肾小管损伤特异性标志物方面的文献进行了整理和分析.一些敏感性好、特异性高的肾小管损伤标志物已在实验研究和临床观察得到了部分验证,如肾损伤分子-1,肾损伤时在肾小管上皮细胞过度表达,对肾肿瘤、缺血性和肾毒性肾损伤的早期诊断敏感性好,且检测稳定性高;肝型脂肪酸结合蛋白,参与肾局部的脂质代谢,对肾近端小管的特异性很高,其尿液含量变化在多种类型的急

  7. Percutaneous Renal Tumor Ablation: Radiation Exposure During Cryoablation and Radiofrequency Ablation

    Energy Technology Data Exchange (ETDEWEB)

    McEachen, James C., E-mail: james.mceachen2@gmail.com [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Leng, Shuai; Atwell, Thomas D. [Mayo Clinic, Department of Radiology (United States); Tollefson, Matthew K. [Mayo Clinic, Department of Urology (United States); Friese, Jeremy L. [Mayo Clinic, Department of Radiology (United States); Wang, Zhen; Murad, M. Hassan [Mayo Clinic, Division of Preventive, Occupational, and Aerospace Medicine (United States); Schmit, Grant D. [Mayo Clinic, Department of Radiology (United States)

    2016-02-15

    IntroductionOnce reserved solely for non-surgical cases, percutaneous ablation is becoming an increasingly popular treatment option for a wider array of patients with small renal masses and the radiation risk needs to be better defined as this transition continues.Materials and MethodsRetrospective review of our renal tumor ablation database revealed 425 patients who underwent percutaneous ablation for treatment of 455 renal tumors over a 5-year time period. Imparted radiation dose information was reviewed for each procedure and converted to effective patient dose and skin dose using established techniques. Statistical analysis was performed with each ablative technique.ResultsFor the 331 cryoablation procedures, the mean DLP was 6987 mGycm (SD = 2861) resulting in a mean effective dose of 104.7 mSv (SD = 43.5) and the mean CTDI{sub vol} was 558 mGy (SD = 439) resulting in a mean skin dose of 563.2 mGy (SD = 344.1). For the 124 RFA procedures, the mean DLP was 3485 mGycm (SD = 1630) resulting in a mean effective dose of 50.3 mSv (SD = 24.0) and the mean CTDI{sub vol} was 232 mGy (SD = 149) resulting in a mean skin dose of 233.2 mGy (SD = 117.4). The difference in patient radiation exposure between the two renal ablation techniques was statistically significant (p < 0.001).ConclusionBoth cryoablation and RFA imparted an average skin dose that was well below the 2 Gy deterministic threshold for appreciable sequela. Renal tumor cryoablation resulted in a mean skin and effective radiation dose more than twice that for RFA. The radiation exposure for both renal tumor ablation techniques was at the high end of the medical imaging radiation dose spectrum.

  8. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells.

    Science.gov (United States)

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

    Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  9. Short Term Clinical Outcome after Laparoscopic Cryoablation of the Renal Tumor < or = 3.5 cm.

    Science.gov (United States)

    Polascik, T J; Nosnik, I; Mayes, J M; Mouraviev, V

    2007-12-01

    Between September 2000 and September 2006, 26 patients underwent primary laparoscopic cryosurgical procedures (28) for an organ-confined renal tumor(s). In one case, cryosurgery was done sequentially on both kidneys. All patients had been carefully selected based on the following criteria: tumor size < or = 3.5 cm, the absence of local and systemic spread on cross-sectional computed tomography (CT) or magnetic resonance imaging (MRI), and the ability to tolerate general anesthesia. A pure laparoscopic approach was employed using third generation cryotechnology (Galil Medical Inc., Plymouth Meeting, USA). Patients were followed by serial CT or MRI scan, creatinine level, and physical examination at least every six months after cryotherapy. The mean patient age was 64 years (range: 44-79) and the mean follow-up was 20.9 +/- 17.2 months. The median tumor size was 2.0 cm (range: 1-3.5 cm). Only one patient required a blood transfusion and one patient developed a transient ileus. The median length of stay was 2.0 days (range: 0-9 days). The median change in creatinine was 0.1 mg/dl (range:-0.4 to 1.8). No patient was converted to open surgery. No evidence of recurrence or progression was found in all patients, and overall survival rate was 100%. Laparoscopic renal cryoablation of the small renal tumor is a safe procedure with minimal complications. Although there were no recurrences with short term follow-up, further long term study is needed to verify its efficacy.

  10. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    NARCIS (Netherlands)

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypoth

  11. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    Science.gov (United States)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  12. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma.

    Science.gov (United States)

    Younes, E; Haas, G P; Dezso, B; Ali, E; Maughan, R L; Kukuruga, M A; Montecillo, E; Pontes, J E; Hillman, G G

    1995-10-15

    We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.

  13. Clinical value analysis of renal tubular epithelium and renal local pathological changes on kidney stone formation%肾小管上皮及肾脏局部病理改变对肾结石形成的临床价值分析

    Institute of Scientific and Technical Information of China (English)

    邓武成

    2015-01-01

    目的:探讨肾小管上皮及肾脏局部病理改变在肾结石形成中的作用机制。方法:选取89例肾结石患者作为实验组,90例肾癌患者的肾标本作为对照组,检测两组肾小管上皮的骨桥蛋白、骨形成蛋白‐2(BM P‐2)和II型胶原的表达情况。结果:实验组患者结石多以混合的形式存在;两组肾小管上皮及肾脏局部病理改变中均可见骨桥蛋白表达,实验组高于对照组,差异有统计学意义,骨桥蛋白主要在肾集合管和肾小管上皮细胞胞浆内表达;BM P‐2、II型胶原在肾小管上皮及肾脏病理局部组织中均未见表达。结论:骨桥蛋白在肾结石患者的肾小管上皮细胞中表达, BM P‐2、II型胶原未见表达,因此肾小管上皮及肾脏局部病理改变时骨桥蛋白可能促进肾结石的形成。%Objective:To study the role of renal tubular epithelium and kidney local pathological changes in kidney stone formation .Methods:89 cases of renal calculi patients were selected as the experimental group ,90 cases of patients with renal cell carcinoma renal specimens as control group ,the expression of renal tubular epithelial osteopontin ,bone morphogenetic protein‐2 (BMP‐2) and type II collagen were detected .Results:The calculi mostly existed in the form of mixture ,including of mixture was the calcium calculi (91 .01% ) ,calcium oxalate calculi (84 .27% ) ,uric acid/uric acid salt (14 .61% ) ,carbonate apatite (8 .99% ) ,and ammonium magnesium phosphate hexahydrate (11 .24% ) .Osteopontin was expressed in both two groups and the experimental group was significantly higher than that in the control group .Osteopontin was mainly expressed in the cytoplasm of renal collecting renal tu‐bular epithelial cells .Expression of BMP‐2 and collagen II were not observed in renal tubular epithelial or renal path‐ological local tissues .Conclusion:Osteopontin is expressed in the renal tubular epithelial cells

  14. Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

    Science.gov (United States)

    Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

    2017-07-21

    Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.Modern Pathology advance online publication, 21

  15. Double Primary Tumors-Renal Cell Carcinoma and Duodenal Mucinous Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Dejan Vuckovic

    2012-12-01

    Full Text Available A 59-year old patient was admited to the Gastroenterology Clinic with the signs of gastrointestinal bleeding. Computerized tomography (CT and a barium-meal radiography revealed a circumferential nodular wall narrowing and incomplete stricture at the D2 part of the duodenum. CT also showed a poorly demarcated mass in the upper and lower poles of the left kidney. During the operation, the whole kidney together with the tumor was removed and also a part of the duodenum. Morphological features of both tumors were typical and distinctive enough to set the diagnosis of two independent primary tumors. The possibility of one being the metastasis of the other was excluded. The diagnosis of double primary malignant neoplasms - renal cell carcinoma and duodenal mucinous adenocarcinoma was made.

  16. Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma.

    Science.gov (United States)

    Bousquet, Guilhem; El Bouchtaoui, Morad; Leboeuf, Christophe; Battistella, Maxime; Varna, Mariana; Ferreira, Irmine; Plassa, Louis-François; Hamdan, Diaddin; Bertheau, Philippe; Feugeas, Jean-Paul; Damotte, Diane; Janin, Anne

    2015-08-07

    Renal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53-expressing tumor cells and TP53 gene abnormalities.We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC.

  17. Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma.

    Science.gov (United States)

    Ning, Hao; Shao, Qian-Qian; Ding, Ke-Jia; Gao, De-Xuan; Lu, Qing-le; Cao, Qing-Wei; Niu, Zhi-Hong; Fu, Qiang; Zhang, Chun-Huan; Qu, Xun; Lü, Jia-Ju

    2012-06-01

    Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P Tregs was higher than that of peripheral blood Tregs in patients with RCC (P Tregs was shown to significantly correlate with the pathological stage (P Tregs and VEGF protein expression (r = 0.51, P Tregs and MVD score (r = 0.39, P Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.

  18. Absence of loss of heterozygosity of BRCA1 in a renal tumor from a BRCA1 germline mutation carrier

    OpenAIRE

    Alanee, Shaheen; Shah, Sohela; Murali, Rajmohan; Rau-Murthy, Rohini; Kasmintan A Schrader; Offit, Kenneth

    2013-01-01

    BRCA1 functions as a tumor suppressor gene and germline and somatic mutations in this gene have been shown to be associated with many types of cancer. We report the first tumor study of renal cell carcinoma in a carrier of the deleterious BRCA1 mutation-c.68_69delAG.

  19. Perfusion-CT monitoring of cryo-ablated renal cells tumors

    Directory of Open Access Journals (Sweden)

    Vespasiani Giuseppe

    2009-10-01

    Full Text Available Abstract Background No single and thoroughly validated imaging method in monitoring of cryoablated renal cell carcinoma (RCC is available. The purpose of our study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (pCT in evaluating the hemodynamic response of RCC. Methods 15 patients (14 male, 1 female; age range, 43-81 years; mean age, 62 years with cryoablated RCC via a transperitoneal approach, underwent to pCT 6-8 months after cryo-therapy. pCT was performed for 65 seconds after intravenous injection of contrast medium (80 mL, 370 mg iodine per millilitre, 4 mL/sec. Perfusion parameters (Time/Density curve; Blood flow, BF; Blood Volume, BV; Mean Transit Time, MTT; Permeability-Surface Area Product, PS were sampled in the cryoablated tumor area and in ipsilateral renal cortex using deconvolution-based method. A tumor was considered to be not responsive to treatment by CT evidence of pathological contrast enhancement in the cryoablated area or renal mass persistence compared with the preoperative CT control. Written informed consent was obtained from all participants before the study. Results After cryotherapy, successfully ablated tumor (n = 13 showed decrease in BV (5,39 +/- 1,28 mL/100 g, BF (69,92 +/- 20,12 mL/100 g/min and PS (16,66 +/- 5,67 mL/100 g/min value and increased value of MTT (25,35 +/- 4,3 sec compared with those of normal renal cortex (BV: 117,86 +/- 31,87 mL/100 g/min; BF: 392,39 +/- 117,32 mL/100 g/min; MTT: 18,02 +/- 3,6 sec; PS: 81,68 +/- 22,75 mL/100 g/min. In one patient, assessment of perfusion parameters was not feasible for breathing artifacts. One tumor showed poor response to treatment by the evidence of nodular contrast enhancement in the region encompassing the original lesion. Two typical enhancement patterns were obtained comparing the Time-Density curves of responsive and not responsive ablated tumors. Conclusion Perfusion CT seems to be a feasible and promising technique in

  20. Bilateral renal tumors in an adult man with Smith-Magenis syndrome: The role of the FLCN gene.

    Science.gov (United States)

    Dardour, Leila; Verleyen, Pieter; Lesage, Karl; Holvoet, Maureen; Devriendt, Koen

    2016-10-01

    Smith-Magenis syndrome (SMS) is a contiguous-gene disorder most commonly caused by a deletion of chromosome 17p11.2. We report a 57 year-old man with SMS who presents bilateral renal tumors. This is most likely related to haploinsufficiency of FLCN gene, located in the deleted region, and a known tumor suppressor gene. Haploinsufficiency of FLCN causes Birt-Hogg-Dubé syndrome (BHDS), characterized by pulmonary cysts, renal and skin tumors. The present observation suggests that the follow-up of patients with SMS should also focus on possible manifestations of BHDS.

  1. Laparoscopic Non-clamping Tumor Enucleation of Renal Hilum Schwannoma in a Single Kidney: A Case Report

    Directory of Open Access Journals (Sweden)

    Fuminari Hanashima

    2015-11-01

    Full Text Available A 56-year-old woman underwent laparoscopic right nephrectomy due to pyonephrosis associated with right ureteral stones. Moreover, the patient developed a brain stem hemorrhage and became bedridden. At the time of nephrectomy, a renal tumor, with a size of 24 × 24 × 20 mm, was observed in the left renal hilum; the tumor did not show contrast enhancement on computed tomography. After 3 years, the tumor gradually grew to a size of 45 × 35 × 34 mm, and therefore, laparoscopic non-clamping tumor enucleation was performed. Pathological examination confirmed a diagnosis of renal schwannoma.

  2. The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma.

    Science.gov (United States)

    Hu, Susie L; Chang, Anthony; Perazella, Mark A; Okusa, Mark D; Jaimes, Edgar A; Weiss, Robert H

    2016-08-01

    Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel-Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist's tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist's tumor.

  3. Robotic partial nephrectomy for renal cell carcinomas with venous tumor thrombus.

    Science.gov (United States)

    Abaza, Ronney; Angell, Jordan

    2013-06-01

    To describe the first report of robotic partial nephrectomies (RPNs) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Partial nephrectomy for RCC extending into the renal vein has been described in limited fashion, but such a complex procedure has not previously been reported in minimally-invasive fashion. We demonstrate the feasibility of robotic nephron-sparing surgery despite vein thrombi and the results of the initial four highly-selected patients to have undergone this novel procedure. Two patients underwent RPN for RCC with VTT involving intraparenchymal vein branches, and 2 others had VTT involving the main renal vein. Mean patient age was 65 years (range 50-74 years). Mean tumor size was 7.75 cm (range 4.3-12.8 cm) with mean RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score of 9.75 (range 8-12). Mean warm ischemia time was 24.2 minutes (range 19-27 minutes) and mean estimated blood loss was 168.8 mL (range 100-300 mL). No patients required transfusion, and there were no intraoperative complications. No patients required conversion to open or standard laparoscopic surgery. All 4 patients were discharged home on the first postoperative day. A single postoperative complication occurred in 1 patient who was readmitted with an ileus that resolved spontaneously. All patients had negative surgical margins. Two patients developed metastatic disease on surveillance imaging. RPN in patients with VTT is safe and feasible in selected patients. Given the risk of metastatic disease in patients with pathologic stage T3a RCC, the role of nephron sparing requires further evaluation such that radical nephrectomy remains the standard of care. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Zhiqin Liu

    2016-01-01

    Full Text Available This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway.

  5. Characterization and staging of renal tumors: significance of MRI diagnostics; Charakterisierung und Staging von Nierentumoren: Bedeutung der MRT-Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Kalinka, A.; Gerlach, A.; Arlart, I.P.; Guenes, N.; Hauser, T.K.; Wuerstlin, S. [Inst. fuer Diagnostische und Interventionelle Radiologie, Katharinenhospital Stuttgart (Germany); Bosse, A. [Inst. fuer Pathologie, Katharinenhospital Stuttgart (Germany)

    2006-03-15

    Purpose: Retrospective evaluation of MRI in the diagnosis of renal masses and determination of the correlation of MRI with histology or follow-up. Materials and methods: 46 consecutive patients (13 female, 33 male, mean age 64.7 yrs) with suspected renal tumors were examined with a 1.5T MR scanner using a standardized protocol (TSE T2fs, 2DGRE T1, dynam. ce3DGRE T1fs, ce2DGRE T1fs, ce3DGRE urogram). Results: 142 renal lesions were found with diameters of <2 cm up to 14 x 18 cm. A primary classification as solid and cystic lesions was performed according to MRI criteria. In 29 cases we found lesions bilaterally, in 17 patients only in one kidney, and in four cases we found multifocal renal tumors unilaterally (n=3) or bilaterally (n=1). In 22 patients with renal tumors, cystic lesions could be seen as well. In 19 cases these were uncomplicated cysts, and in 3 cases these were complicated cysts. 35/43 lesions were histologically proven solid vascularized tumors (29 renal cell carcinomas, 6 urothelial carcinomas), five additional masses with tumor signs in MRI appeared to be progressive during follow-up thus suggesting malignancy, and one case was a multifocal bilateral renal tumor. 3/43 lesions were initially reported as being suspected of malignancy but were proven during follow-up or histologically to be benign. Tumor thrombus was depicted in MRI in the renal vein in 5 cases, stretching into the IVC in 4 cases and proven histologically in 4 and 3 cases, respectively. Of these solid masses, 99 cystic lesions could be differentiated clearly in MRI (88 simple cysts, 11 complicated cysts) that remained unchanged during follow-up (6-65 months) or were proven to be cysts histologically. In 17 cases these cysts were bilateral, in 19 cases unilateral, and 33 kidneys showed multicystic changes. In characterizing renal masses, MRI showed a positive predictive value of 93% for the diagnosis of a malignant tumor. The T-stage of histologically proven renal cell carcinomas using

  6. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  7. Effect of nitrendipine on renal function and on hormonal parameters after intravascular iopromide

    DEFF Research Database (Denmark)

    Madsen, J K; Jensen, J W; Sandermann, J

    1998-01-01

    . Renal tubular function was estimated from the clearance of lithium. Hormones were measured by radioimmunoassays. RESULTS: Arteriography with iopromide did not change renal function. No differences between the nitrendipine and placebo groups were found in renal hemodynamics, tubular sodium handling...

  8. Successful Treatment of Extra-Renal Noncerebral Rhabdoid Tumors with VIDE.

    Science.gov (United States)

    Yasui, Naoko; Yoshida, Akihiko; Kobayashi, Eisuke; Nakatani, Fumihiko; Kawamoto, Hiroshi

    2016-02-01

    Extra-renal noncerebral rhabdoid tumors (ERRTs) are highly aggressive and often lethal. An optimal chemotherapy regimen for ERRT remains undetermined. We report on three pediatric patients successfully treated with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE). Two of our patients who had metastatic or refractory disease have survived more than 2 years, one disease free without myeloablative megatherapy. The treatment with high-dose alkylator therapy is reported to have a beneficial effect on survival. A VIDE regimen containing high-dose ifosfamide is feasible and appears to prolong the survival of patients with ERRT. This regimen may be a promising option for ERRT treatment without myeloablative megatherapy.

  9. Skull Base Clear Cell Carcinoma, Metastasis of Renal Primary Tumor: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ilson Sepúlveda

    2013-08-01

    Full Text Available We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.

  10. Renal Tumor

    Directory of Open Access Journals (Sweden)

    Yarisdey Corrales Hernández

    2016-02-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}

  11. Double-echo gradient chemical shift MR imaging fails to differentiate minimal fat renal angiomyolipomas from other homogeneous solid renal tumors

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    Ferré, R., E-mail: kn638@yahoo.fr [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Cornelis, F. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Verkarre, V. [Department of Pathology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Eiss, D.; Correas, J.M. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France); Grenier, N. [Department of Radiology, Pellegrin Hospital, Place Amélie Raba Léon, 33076 Bordeaux (France); Hélénon, O. [Department of Radiology, Necker Hospital, 149 rue de Sèvres, 75730 Paris (France)

    2015-03-15

    Highlights: •Diagnosis of AMLs with minimal fat (mfAMLs) is still challenging with MRI. •Drop of signal on opposed-phase MR imaging is not specific of mfAMLs. •Double-echo gradient-echo sequences cannot accurately differentiate renal mfAMLs from other renal tumors. -- Abstract: Objectives: The purpose of this retrospective study was to evaluate the diagnostic performance of double-echo gradient chemical shift (GRE) magnetic resonance (MR) imaging for the differentiation of angiomyolipomas with minimal fat (mfAML) from other homogeneous solid renal tumors. Methods: Between 2005 and 2010 in two institutions, all histologically proven homogenous solid renal tumors imaged with computed tomography and MR imaging, including GRE sequences, have been retrospectively selected. A total of 118 patients (mean age: 61 years; range: 20–87) with 119 tumors were included. Two readers measured independently the signal intensity (SI) on GRE images and calculated SI index (SII) and tumor-to-spleen ratio (TSR) on in-phase and opposed-phase images. Intra- and interreader agreement was obtained. Cut-off values were derived from the receiver operating characteristic (ROC) curve analysis. Results: Twelve mfAMLs in 11 patients were identified (mean size: 2.8 cm; range: 1.2–3.5), and 107 non-AML tumors (3.2 cm; 1–7.8) in 107 patients. The intraobserver reproducibility of SII and TSR was excellent with an intraclass correlation coefficient equal to 0.99 [0.98–0.99]. The coefficient of correlation between the readers was 0.99. The mean values of TSR for mfAMLs and non-mfAMLs were −7.0 ± 22.8 versus −8.2 ± 21.2 for reader 1 and −6.7 ± 22.8 versus −8.4 ± 20.9 for reader 2 respectively. No significant difference was noticed between the two groups for SII (p = 0.98) and TSR (p = 0.86). Only 1 out of 12 mfAMLs and 11 of 107 non-AML tumors presented with a TSR inferior to −30% (p = 0.83). Conclusion: In a routine practice, GRE sequences cannot be a confident tool to

  12. 缺氧对肾小管上皮细胞分泌外泌体的影响%Effect of hypoxia on exosomes in renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    郭艳霞; 宋秀珍; 周秋根

    2015-01-01

    renal tubular epithelial cells which were cultured in normoxia (21% O2) or hypoxia(1% O2) for 48 h was collected and centrifuged gradiently to harvest exosomes.Exosomes were identified and compared by transmission electron microscope, nanoparticle tracking analysis, Western blotting and measurement of the protein concentration.(2) Primary peritoneal macrophages of rats were co-cultured with exosomes in different concentrations (1, 10, 50, 100, 300 mg/L).The expression of interleukin-6(IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) in cells and supernatant were separately detected by quantitative real-time PCR (qRT-PCR) and ELISA, and the expression of phospho (p)-STAT/STAT and suppressors of cytokine signaling 1 (SOCS1) in macrophages was detected by Western blotting.At last, the expression of inflammatory microRNAs (miR) in exosomes was measured by qRT-PCR.Results (1) The vesicles harvested by gradient centrifugation were less than 150 nm and expressed CD63 which was characteristic of exosomes.Hypoxia had no effect on the morphology of exosomes, but stimulated their secretion.(2) Hypoxic exosomes dose-dependently improved the expression of IL-6, TNF-α, iNOS in macrophages polarized by lipopolysaccharide (LPS) and increased the expression of p-STAT while decreased the expression of SOCS1 (P < 0.01).MicroRNAs referred to inflammation such as miR-155 and miR-27a increased in hypoxic exosomes compared to that in normoxic exosomes (P < 0.05).Conclusions Hypoxia makes exosomes promoted the polarization of macrophages to M1, which may account for the microinflammation in chronic kidney diseases.

  13. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1988-01-01

    patients had some form of renal acidification defect; 8 had the distal type of renal tubular acidosis, 2 the complete and 6 the incomplete form. One patient had proximal renal tubular acidosis. These findings, which suggest that renal acidification defects play an important role in the pathogenesis...

  14. [Renal tumors: The International Society of Urologic Pathology (ISUP) 2012 consensus conference recommendations].

    Science.gov (United States)

    Rioux-Leclercq, Nathalie; Ferran, Algaba; Mahul, Amin; Argani, Pedram; Billis, Athanase; Bonsib, Stephen; Cheng, Liang; Cheville, John; Eble, John; Egevad, Lars; Epstein, Jonathan; Grignon, David; Hes, Ondrej; Humphrey, Peter; Magi-Galluzzi, Cristina; Martignoni, Guido; McKenney, Jesse; Merino, Maria; Moch, Holger; Montironi, Rodolfo; Netto, George; Reuter, Viktor; Samaratunga, Hemamali; Shen, Steven; Srigley, John; Tamboli, Pheroze; Tan, Puay Hoon; Tickoo, Satish; Trpkov, Kiril; Zhou, Ming; Delahunt, Brett; Comperat, Eva

    2014-12-01

    During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Efeito do extrato bruto das folhas de Echinodorus Macrophyllus e de frações semipurificadas sobre a função renal em ratos com necrose tubular aguda induzida por gentamicina

    OpenAIRE

    Gustavo Pereira Cosenza

    2010-01-01

    A Echinodorus macrophyllus (E. macrophyllus), família alismatacea, é uma espécie nativa do Brasil onde é conhecida por chapéu de couro, chá mineiro e erva de pântano. O objetivo deste trabalho foi avaliar o possível efeito do extrato bruto das folhas de E. macrophyllus (EB) e de frações dele extraídos (FAE, FB e FAq) sobre a função renal em ratos normais e em ratos com necrose tubular aguda (NTA) induzida por gentamicina (GT). O EB, obtido por percolação, foi submetido à extração com acetato ...

  16. 30-MM Tubular Projectile

    Science.gov (United States)

    1984-10-01

    Suiza tubular projectile 20 9. Inspection of Hispano Suiza sabot 21 10. Inspection of GAU-8 sabot 22 11. Firing data - 30-rn tubular projectile (Hispano... Suiza 23 copper banded) 12. Firing data - 30-m tubular projectile (GAU-8 plastic 24 banded) 13. Firing data - 30-m tubular projectile (GAU-8 copper 25...42 13. In-flight Hispano Suiza tubular projectiles 43 14. In-flight C4U-8 (plastic) tubular projectile 44 15. In-flight GCU-8 (copper) tubular

  17. Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study.

    Science.gov (United States)

    Cozzi, Denis A; Ceccanti, Silvia; Frediani, Simone; Mele, Ermelinda; Cozzi, Francesco

    2013-09-01

    Mild-to-moderate renal function loss may be an independent risk factor for cardiovascular disease and overall mortality. As in adults with renal carcinoma nephrectomy is associated with an high risk for moderate renal function loss, we aimed to assess the renal function adaptation over a long period of time in children with unilateral renal tumor (URT). Seventy-two children who underwent surgery for URT were enrolled in this study. Glomerular filtration rate was estimated (eGFR) with the Modification of Diet in Renal Study or the Schwartz equation, as appropriate for the age. Twelve patients treated by nephron-sparing surgery (Group A) and 42 treated by nephrectomy (Group B) had an age between 2 and 30 years; 18 patients treated by nephrectomy had an age between 33 and 51 years (Group C). At cross-sectional follow-up 8% patients of Group A, 42% of Group B and 78% of Group C presented a mild-to-moderate renal function. The longitudinal data stratified by post-operative intervals showed that patients of Group C presented a significant progressive decrease in mean ± standard deviation eGFR (88.1 ± 22.6 during the third decade after surgery vs. 66.6 ± 15.6 ml/min/1.73 m(2) during the fifth decade after surgery; P = 0.02). The longitudinal data stratified by age showed that patients with an age between 45 and 54 years presented a mean eGFR significantly lower than that expected for the physiological renal function decline with aging (P = 0.001). Aging is associated with a mild-to-moderate renal function loss in many adult patients following nephrectomy during childhood for URT. Copyright © 2013 Wiley Periodicals, Inc.

  18. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

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    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  19. Supra-Acetabular Brown Tumor due to Primary Hyperparathyroidism Associated with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Rosaria M. Ruggeri

    2010-01-01

    Full Text Available A 63-year-old woman presented to the Orthopedic Unit of our hospital complaining of right hip pain of 6 months'duration associated with a worsening limp. Her past medical history included chronic renal insufficiency. Physical examination revealed deep pain in the iliac region and severe restriction of the right hip's articular function in the maximum degrees of range of motion. X-rays and CT scan detected an osteolytic and expansive lesion of the right supra-acetabular region with structural reabsorption of the right iliac wing. 99mTc-MDP whole-body bone scan showed an abnormal uptake in the right iliac region. Bone biopsy revealed an osteolytic lesion with multinucleated giant cells, indicating a brown tumor. Serum intact PTH was elevated (1020 pg/ml; normal values, 12 62 pg/ml, but her serum calcium was normal (total = 9.4 mg/dl, nv 8.5–10.5; ionized = 5.0 mg/dl, nv 4.2–5.4 due to the coexistence of chronic renal failure. 99mTc-MIBI scintigraphy revealed a single focus of sestamibi accumulation in the left retrosternal location, which turned out to be an intrathoracic parathyroid adenoma at surgical exploration. After surgical removal of the parathyroid adenoma, PTH levels decreased to 212 pg/ml. Three months after parathyroidectomy, the imaging studies showed complete recovery of the osteolytic lesion, thus avoiding any orthopedic surgery. This case is noteworthy because (1 primary hyperparathyroidism was not suspected due to the normocalcemia, likely attributable to the coexistence of chronic renal failure; and (2 it was associated with a brown tumor of unusual location (right supra-acetabular region.

  20. Correlation between Dynamic Spiral-CT Enhancement Parameters and Tumor Angiogenesis in Renal Cell Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jinhong Wang; Weixia Chen; Xiuhui Zhang; Pengqiu Min; Rongbo Liu; Hengxuan Yang

    2005-01-01

    OBJECTIVE To prospectively investigate the correlation between the enhancement parameters of a dynamic-CT (D-CT) scan for renal cell carcinomas (RCC) and the carcinoma tissue microvessel density (MVD) in renal cell carcinomas (RCC).METHODS Twenty-four cases of renal cell carcinoma verifyied by histopathology were scanned via dynamic-CT, followed by a whole kidney scan. Enhancement parameters were derived as follows .The slope of the contrast media uptake curve (S), area under the curve(AR), the density difference before and after tissue enhancement (△HU) and tissue blood ratio (TBR) were calculated for all lesions. Time-density curve types were ranked from the lowest to the highest of the slope of the contrast media uptake curve (S) as type A, B and C. Pathologic slides corresponding to the CT imagings were subjected to CD34 monoclonal antibodies, then were evaluated with an image analyzer to count hot spots of MVD. By using the Spearman rank correlation tests, statistical analysis was performed to determine the strength of the relationship between enhancement parameters and MVD determinations.RESULTS The carcinoma tissue MVD showed a direct correlation with the enhancement parameters of D-CT (r=0.54, r=0.62, r=0.55, r=0.64, r=0.44,P< 0.05). Moreover the S, △HU, TBR and type curves all demonstrated a strong correlation with the MVD. By analyzing the various enhancement parameters of the time-density curves, the relationship between the enhancement CT parameters corresponding to the tumor's MVD was identified.CONCLUSION A dynamic spiral-CT scan may be a helpful method as a measurement of tumor angiogenesis in vivo in RCC.

  1. [Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)].

    Science.gov (United States)

    Kristiansen, G; Delahunt, B; Srigley, J R; Lüders, C; Lunkenheimer, J-M; Gevensleben, H; Thiesler, T; Montironi, R; Egevad, L

    2015-05-01

    The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.

  2. Renal Tumor Cryoablation Planning. The Efficiency of Simulation on Reconstructed 3D CT Scan

    Directory of Open Access Journals (Sweden)

    Ciprian Valerian LUCAN

    2010-12-01

    Full Text Available Introduction & Objective: Nephron-sparing surgical techniques risks are related to tumor relationships with adjacent anatomic structures. Complexity of the renal anatomy drives the interest to develop tools for 3D reconstruction and surgery simulation. The aim of the article was to assess the simulation on reconstructed 3D CT scan used for planning the cryoablation. Material & Method: A prospective randomized study was performed between Jan. 2007 and July 2009 on 27 patients who underwent retroperitoneoscopic T1a renal tumors cryoablation (RC. All patients were assessed preoperatively by CT scan, also used for 3D volume rendering. In the Gr.A, the patients underwent surgery planning by simulation on 3D CT scan. In the Gr.B., patients underwent standard RC. The two groups were compared in terms of surgical time, bleeding, postoperative drainage, analgesics requirement, hospital stay, time to socio-professional reintegration. Results: Fourteen patients underwent preoperative cryoablation planning (Gr.A and 13 patients underwent standard CR (Gr.B. All parameters analyzed were shorter in the Gr.A. On multivariate logistic regression, only shortens of the surgical time (138.79±5.51 min. in Gr.A. vs. 140.92±5.54 min in Gr.B. and bleeding (164.29±60.22 mL in Gr.A. vs. 215.38±100.80 mL in Gr.B. achieved statistical significance (p<0.05. The number of cryoneedles assessed by simulation had a 92.52% accuracy when compared with those effectively used. Conclusions: Simulation of the cryoablation using reconstructed 3D CT scan improves the surgical results. The application used for simulation was able to accurately assess the number of cryoneedles required for tumor ablation, their direction and approach.

  3. Natural history of untreated renal cell carcinoma with venous tumor thrombus.

    Science.gov (United States)

    Reese, Adam C; Whitson, Jared M; Meng, Maxwell V

    2013-10-01

    The natural history of untreated renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is poorly characterized. We aimed to describe the natural history of this disease, and to identify prognostic factors associated with disease-specific survival. We identified patients in the Surveillance, Epidemiology, and End Results (SEER) database with untreated renal cell carcinoma and venous tumor thrombi. Disease-specific median and 1-year survival rates were determined, and disease-free survival curves were plotted using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to identify factors associated with disease-specific and overall survival in this patient group. Of 2,265 patients with RCC and VTT, 390 (17%) underwent no treatment; 278 (71%) patients died during follow-up; of these, 243 deaths (87%) were due to RCC. Median and 1-year disease-specific survival for this group was 5 months and 29%, respectively. On multivariable analysis, the extent of tumor thrombus (HR 1.7 for T3c vs. T3b, 95% CI 1.0-2.7) and the presence of metastases (HR 3.1 for M+ vs. M0, 95% CI 1.7-5.5) were most strongly associated with disease-specific mortality. Prognosis is poor for the majority of untreated patients with RCC and VTT. Supradiaphragmatic thrombi and distant metastases are adverse prognostic factors in this patient group. This information is important when counseling patients as to the risk and benefits of surgical vs. nonoperative management of RCC and VTT. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Tumor perfusion assessed by dynamic contrast-enhanced MRI correlates to the grading of renal cell carcinoma: Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Palmowski, Moritz, E-mail: mpalmowski@ukaachen.d [Department of Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen (Germany); Department of Diagnostic Radiology, Medical Faculty, RWTH Aachen University, Aachen (Germany); Schifferdecker, Isabel [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany); Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany); Zwick, Stefan [Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany); Macher-Goeppinger, Stephan [Institute of Pathology, Heidelberg University, Heidelberg (Germany); Laue, Hendrik [MeVis Research, Center for Medical Image Computing, Bremen (Germany); Haferkamp, Axel [Department of Urology, Heidelberg University (Germany); Kauczor, Hans-Ulrich [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany); Kiessling, Fabian [Department of Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen (Germany); Hallscheidt, Peter [Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg (Germany)

    2010-06-15

    In this study, we investigated whether assessment of the tumor perfusion by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) enables to estimate the morphologic grading of renal cell carcinomas. A total of 21 patients with suspected renal cell cancer were examined using a Gadobutrol-enhanced, dynamic saturation-recovery, turbo-fast, low-angle shot sequence. Tumor perfusion and the tissue-blood ratio within the entire tumor and the most highly vascularized part of the tumor were calculated according to the model of Miles. Immediately after examination, patients underwent surgery, and the results from imaging were compared with the morphological analysis of the histologic grading. Fourteen patients had G2 tumors, and seven patients had G3 tumors. Significantly higher perfusion values (p < 0.05) were obtained in G3 tumors than in G2 tumors when the entire tumor area was considered (1.59 {+-} 0.44 (ml/g/min) vs. 1.08 {+-} 0.38 (ml/g/min)) or its most highly vascularized part (2.14 {+-} 0.89 (ml/g/min) vs. 1.40 {+-} 0.49 (ml/g/min)). By contrast, the tissue-blood ratios did not differ significantly between the two groups. In conclusion, unlike tissue-blood ratio, surrogate parameters of the tumor perfusion determined by DCE MRI seem to allow an estimation of the grading of renal cell carcinoma. However, further studies with high case numbers and including patients with G1 tumors are required to evaluate the full potential and clinical impact.

  5. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management.

    Science.gov (United States)

    Vollherbst, Dominik; Bertheau, Robert; Kauczor, Hans-Ulrich; Radeleff, Boris Alexis; Pereira, Philippe L; Sommer, Christof-Matthias

    2017-03-01

    Background Radiofrequency ablation (RFA) is an established treatment for small renal tumors. The objective of this review is to systematically assess the type, frequency, risk factors and management of treatment failure after image-guided percutaneous RFA of renal tumors. Method 10 studies (967 patients, 1033 tumors) with a mean/median follow-up of ≥ 30 months were systematically identified and analyzed. Results and Conclusion Image-guided percutaneous RFA of localized renal tumors is very effective. The most common type of treatment failure is residual unablated tumor (5.9 %), followed by local tumor progression (4.7 %). De novo tumors in the kidneys occur in 1.3 % of cases and extra-renal metastases in 2.0 %. Local tumor progression, de novo tumors in the kidneys and extra-renal metastases occur predominantly later than 12 months after initial RFA. Tumor size > 3 cm and central tumor location are the major risk factors for treatment failure. In the case of treatment failure, repeated RFA shows high success rates (86.3 % for residual unablated tumors and 87.5 % for local tumor progression). Key Points: · Treatment failure can be subdivided into residual unablated tumor and local tumor progression.. · Residual unablated tumor occurs in 5.9 % of cases.. · Local tumor progression occurs in 4.7 % of cases.. · Tumor size and location are the major risk factors for treatment failure.. · Repeated RFA is effective and commonly used for management.. Citation Format · Vollherbst D, Bertheau R, Kauczor H et al. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management. Fortschr Röntgenstr 2017; 189: 219 - 227.

  6. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Sung Min Ju

    2015-01-01

    Full Text Available Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2 cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.

  7. Craniofacial brown tumor as a result of secondary hyperparathyroidism in chronic renal disease patient: A rare entity

    Science.gov (United States)

    Verma, Pradhuman; Verma, Kanika Gupta; Verma, Dinesh; Patwardhan, Nitin

    2014-01-01

    Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to primary or secondary hyperparathyroidism resulting in a local destructive phenomenon. The differential diagnosis based on histological examination is only presumptive. Clinical, radiological and laboratory data are necessary for definitive diagnosis. Here, we report a very rare case of brown tumor involving maxilla and mandible, which is the result of secondary hyperparathyroidism in 30-year-old female patient with chronic renal disease. PMID:25328310

  8. [Radical nephrectomy and thrombectomy in patients with renal cell cancer complicated by tumoral thrombosis of the renal vein and vena cava inferior].

    Science.gov (United States)

    Rusyn, V I; Korsak, V V; Rusyn, A V; Boĭko, S O

    2013-01-01

    Surgical treatment was conducted in 81 patients, suffering renocellular cancer (RCC), complicated by a renal vein and vena cava inferior thrombosis. According to the Mayo clinic classification, the level of a tumoral thrombus spread was established: the 0 level--in 37 patients, the level I--in 19, the level II--in 17, the level III --in 6, and the level IV--in 2. There were substantiated the optimal surgical accesses and technique of radical nephrectomy and thrombectomy for RCC, complicated by a renal vein and vena cava inferior thrombosis. It is recommended to apply transabdominal accesses: the extended median laparotomic, bilateral subcostal of a "Chevron" or "Mercedes" type. There was shown, that the access choice depends on the level of the tumoral thrombus localization.

  9. Does a venous tumor thrombus exclude renal transitional cell carcinoma? Implications for neo-adjuvant treatment strategies.

    Science.gov (United States)

    Huber, Johannes; Teber, Dogu; Hatiboglu, Gencay; Popeneciu, Valentin; Jakobi, Hildegard; Hallscheidt, Peter; Pahernik, Sascha; Hohenfellner, Markus

    2014-02-01

    A venous tumor thrombus (VTT) is well-known in renal cell carcinoma, but we experienced a series of five patients with VTT due to renal transitional cell carcinoma (TCC). Our study aimed to determine the incidence and clinical relevance of this entity. From our prospectively-maintained tumor database, we identified 102 patients with renal TCC according to postoperative histology and analyzed the incidence of VTT in renal TCC from 1990 to 2010. Five out of 102 patients with TCC (5%) had a VTT. None of these five patients experienced gross haematuria and we presumed correct diagnosis preoperatively in one out of five patients. Univariate analysis revealed that TNM stage and resection status were inferior in the VTT group. All five patients from the VTT group died from their disease, with a median survival of 8.9 months. With regard to all diagnosed VTT, the effective incidence of vena cava involvement in RCC was 48-fold higher than in renal TCC. A VTT is very suggestive of renal cell carcinoma. However, before neo-adjuvant treatment, the diagnosis should be assured whenever there is doubt.

  10. A rare case of TFE-related pigmented renal tumor with overlapping features between melanotic Xp11 translocation renal cancer and Xp11 renal cell carcinoma with melanotic features.

    Science.gov (United States)

    Cardili, Leonardo; Wrublevsky Pereira, Gregório; Viana, Cristiano Ribeiro

    2017-02-16

    In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3-related pigmented renal tumor showing unusual immunoexpression of cytokeratins (AE1/AE3) and renal cell carcinoma markers (RCC, CD10). Cathepsin-K and Vimentin were diffusely positive whereas melanocytic markers (HMB-45 and Melan-A) displayed weak and patchy expression. We found no labelling for PAX-8, muscle markers (desmin, smooth muscle actin, muscle-specific actin and caldesmon) and S-100. TFE3 fusion was confirmed by break-apart fluorescence in situ hybridization (FISH). This case corroborates previous evidence for overlap in the TFE3-associated cancer family and illustrates that it may not be possible to set a clear cutoff between epithelial (XRCCM) and mesenchymal (MXTRC) subgroups.

  11. Why should survivors of childhood renal tumor and others with only one kidney be denied the chance to play contact sports?

    Science.gov (United States)

    Spreafico, Filippo; Terenziani, Monica; van den Heuvel-Eibrink, Marry M; Pritchard-Jones, Kathy; Levitt, Gill; Graf, Norbert; Bergeron, Christophe; Massimino, Maura

    2014-04-01

    Over the last few decades advances in the treatment of childhood and young adult cancer have greatly improved survival. As a result most children diagnosed with Wilms' tumor (the most common renal tumor in childhood) or other renal tumors become long-term survivors, living with surgically solitary kidneys. As physical activity is gaining credibility as a therapy enhancing well-being, encouraging cancer survivors do exercise during adolescence and adulthood is advisable. Discussing current evidence-based information would help to provide a framework for the harmonization of guidelines for sport participation of childhood and young adult renal tumor survivors.

  12. Presentación sincrónica de cáncer colorrectal y tumor renal

    OpenAIRE

    JENSEN B,CHRISTIAN; RIFFO R,RODRIGO; MARTINEZ R,NICOLÁS; VALENZUELA V,ANTONIA

    2007-01-01

    Introducción: La presencia simultánea de dos cánceres primarios en el organismo es un evento de baja frecuencia. La presentación sincrónica de cáncer colorectal y renal es un ejemplo de esto, con una prevalencia entre el 0,33-0,5% de tumores renales en pacientes portadores de cáncer colorrectal. Objetivos: Determinar la frecuencia de presentación simultánea de cáncer colorectal y tumor renal en nuestro medio, y analizar el manejo de esta doble patología desde el punto de vista quirúrgico. Mat...

  13. 159. Trombectomía de Vena Cava Inferior Por Invasión de Tumor Renal

    Directory of Open Access Journals (Sweden)

    N. Miranda

    2012-04-01

    Conclusiones: en casos seleccionados, el carcinoma de célula renal extendiéndose a VCI puede ser resecado sin dificultad sin necesidad de esternotomía, CBP o PCHP, constituyendo una alternativa curativa en el tratamiento de dichos tumores.

  14. P16 and p53 expression in (pre)malignant epidermal tumors of renal transplant recipients and immunocompetent individuals.

    NARCIS (Netherlands)

    Blokx, W.A.M.; Jong, E.M.G.J. de; Wilde, P.C.M. de; Bulten, J.; Link, M.M.G.M.; Ruiter, D.J.; Kerkhof, P.C.M. van de

    2003-01-01

    Ultraviolet (UV) radiation is a prevailing factor implicated in the etiology of keratinocytic intraepidermal neoplasia (KIN) and squamous cell carcinomas (SCCs), as evidenced by the high frequency of UV-related mutations in the p53 and p16 tumor suppressor genes. In renal transplant recipients (RTRs

  15. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    OpenAIRE

    Néstor Moisés Tineo Araque; Helen Daniela Uzcátegui Camacaro; Henrry Ramírez; Humberto Ruz

    2010-01-01

    El cáncer de riñón representa entre el 2 y 3% del total de las neoplasias malignas, encontrándose entre ellas el tumor neuroectodérmico (1,1% dentro del cáncer renal). En muchos casos el diagnóstico es tardío y se describe la triada clásica: dolor, hematuria y masa palpable. El ultrasonido y la tomografía axial computarizada son los métodos de diagnóstico más importantes y el éxito terapéutico se basa en la cirugía radical. Se presenta caso de paciente femenina de 23 años quien inicia enferm...

  16. Tumor neuroectodérmico primitivo renal. Reporte de un caso

    OpenAIRE

    Néstor Moisés Tineo Araque; Helen Daniela Uzcátegui Camacaro; Henrry Ramírez; Humberto Ruz

    2011-01-01

    El cáncer de riñón representa entre el 2 y 3% del total de las neoplasias malignas, encontrándose entre ellas el tumor neuroectodérmico (1,1% dentro del cáncer renal). En muchos casos el diagnóstico es tardío y se describe la triada clásica: dolor, hematuria y masa palpable. El ultrasonido y la tomografía axial computarizada son los métodos de diagnóstico más importantes y el éxito terapéutico se basa en la cirugía radical. Se presenta caso de paciente femenina de 23 años quien inicia enferm...

  17. The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. 1984.

    Science.gov (United States)

    Neri, Giovanni; Martini-Neri, Maria Enrica; Katz, Ben E; Opitz, John M

    2013-11-01

    The ensuing paper by Professor Giovanni Neri and colleagues was originally published in 1984, American Journal of Medical Genetics 19:195–207. The original article described a new family with a condition that the authors designated as the Perlman syndrome. This disorder, while uncommon, is an important multiple congenital anomaly and dysplasia syndrome; the causative gene was recently identified. This paper is a seminal work and is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al. [1973, 1975] and we propose to call it the "Perlman syndrome." It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed. © 2013 Wiley Periodicals, Inc.

  18. Paraneoplastic Erythropoietin Secreting Tumor of Renal Origin:A Forgotten Endocrine Hormone

    Institute of Scientific and Technical Information of China (English)

    Yaseen Ali; Amila M. Parekh; Rahul K. Rao; Taseen Ali; Jordan Garvey

    2015-01-01

    Paraneoplastic syndromes are a group of disorders associated by the presence of cancer in the human body, but are not caused by the cancer or its metastatic potential. These syndromes are usually the result of cell mediators. For instance, the interleukins and cytokines secreted by the body’s defense system combat with neoplastic cells that inadvertently bind to cell speciifc receptors in the endocrine system due to similar structural morphology and produce undesired side effects. In this article, we presented an interesting case of a 44-year-old male veteran who came to our free clinic for his chronic constipation unmitigated by over the counter laxatives and sought other provider care in the past few months. During our brief clinic visit, his history and examination revealed that he had also been suffering from mild abdominal pain, decrease in appetite, inconvenient reddish plethoric facial appearance and lethargy. A careful review of the history, physical and laboratory examination revealed erythrocytosis and mild hypercalcemia. Meanwhile, a renal mass biopsy was proven to be erythropoietin secreting renal cell tumor. Subsequently, the patient underwent resection and was followed to complete resolution of his symptoms.

  19. Everolimus in the treatment of renal cell carcinoma and neuroendocrine tumors.

    Science.gov (United States)

    Chan, Hiu-yan; Grossman, Ashley B; Bukowski, Ronald M

    2010-08-01

    Renal cell carcinoma (RCC) and neuroendocrine tumors (NET) are uncommon malignancies, highly resistant to chemotherapy, that have emerged as attractive platforms for evaluating novel targeted regimens. Everolimus is an oral rapamycin derivative within the mammalian target of rapamycin class of agents. Preclinical series have shown that everolimus exhibits anticancer effects in RCC and NET cell lines. A phase 3 placebo-controlled study in advanced clear-cell RCC, known as RECORD-1 (for "REnal Cell cancer treatment with Oral RAD001 given Daily"), documented that everolimus stabilizes tumor progression, prolongs progression-free survival and has acceptable tolerability in patients previously treated with the multikinase inhibitors sunitinib and/or sorafenib. Everolimus has been granted regulatory approval for use in sunitinib-pretreated and/or sorafenib-pretreated advanced RCC and incorporated into clinical practice guidelines, and the RECORD-1 safety data are being used to develop recommendations for managing clinically important adverse events in everolimus-treated patients. Ongoing clinical trials are evaluating everolimus as earlier RCC therapy (first-line for advanced disease and as neoadjuvant therapy), in non-clear-cell tumors, and in combination with various other approved or investigational targeted therapies for RCC. Regarding advanced NET, recently published phase 2 data support the ability of everolimus to improve disease control in patients with advanced NET as monotherapy or in combination with somatostatin analogue therapy, octreotide long-acting release (LAR). Forthcoming data from phase 3 placebo-controlled trials of everolimus, one focused on monotherapy for pancreatic NET and the other on combination use with octreotide LAR for patients with advanced NET and a history of carcinoid syndrome, will provide insight into its future place in NET therapy. The results of a number of ongoing phase 3 evaluations of everolimus will determine its broader