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Sample records for childhood iga nephropathy

  1. Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy

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    Seung-Ah Baek

    2010-02-01

    Full Text Available Purpose : Interleukin-17 (IL-17 is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN. Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs in IL-17 receptor A (IL-17RA gene and childhood IgAN. Methods : We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (?#180; and >4 mg/m2/h, ?#180;0 and >40 mg/m2/h, respectively and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>4 mg/m2/h and those without proteinuria (codominant model OR 0.36, 95% CI 0.19–0.66, P<0.001; dominant model OR 0.35, 95% CI 0.17–0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01–1.06 P=0.025. Conclusion : Our results indicate that the SNP in IL-17RA (rs2895332 may be related to the development of proteinuria in IgAN patients.

  2. IgA nephropathy and infections.

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    Rollino, Cristiana; Vischini, Gisella; Coppo, Rosanna

    2016-08-01

    In this paper we concentrate on the role of infections in IgA nephropathy both from a pathogenetic and clinic point of view. The current hypotheses as regards the role of infections in the pathogenesis of IgA nephropathy are: (a) role of particular pathogens, (b) chronic exposure to mucosal infections, (c) abnormal handling of commensal microbes (gut microbiota). We also focus on particular infections reported in association with classic IgA nephropathy (HIV, malaria, Chlamydia, Lyme disease), as well as on IgA dominant-infection-associated glomerulonephritis. This is a unique form of glomerulonephritis, where IgA deposition is dominant. It is mostly recognized in old, diabetic patients and in association with staphylococcal infection. PMID:26800970

  3. Iga nephropathy: clinical-morphologic correlation

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    Basta-Jovanović Gordana M.

    2003-01-01

    Full Text Available IgA nephropathy is glomerular disease caracterized by the presencemorphologic changes as wella as the prognosis is in correlation with of IgA dominant or codominant imunoglobuline deposits in glomer-the amount of proteinuria. The prognosis is better in children. ular mesangium which can be demostrated by immunofluorescence. Clinical manifestations of IgA nephropathy in the majority of cases is hematuria which can be macro or mikroskopic, isolated or combined with proteinuria, which can be of nephrotic range. The prognosis o the disease is better if presented with haematuria. Intensity of????.

  4. Corticosteroid therapy in IgA nephropathy.

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    Lv, Jicheng; Xu, Damin; Perkovic, Vlado; Ma, Xinxin; Johnson, David W; Woodward, Mark; Levin, Adeera; Zhang, Hong; Wang, Haiyan

    2012-06-01

    The benefits and risks of steroids for the treatment of IgA nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion >1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0.32 [95% confidence interval [CI], 0.15-0.67]; P=0.002) and a reduction in proteinuria (weighted mean difference, -0.46 g/d [95% CI, -0.63 to -0.29 g/d]), with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone >30 mg/d or high-dose pulse intravenous methylprednisolone with duration ≤1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA nephropathy requires a high-quality trial with a large sample size. PMID:22539830

  5. TRAC Variants Associate with IgA Nephropathy

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    Li, Ru; Xue, Chao; Li, Caixia; Lou, Tanqi; Tao, Yu; Li, Youji; Huang, Weijun; Zhang, Jun; Leung, Joseph C. K.; Lam, Man F.; Vyse, Tim J.; Kar N. Lai; Wu, Changyou; Wang, Yiming

    2009-01-01

    The T cell receptor alpha constant gene (TRAC) encodes the constant region of the α chain for the T cell receptor, and the association of its gene variants with IgA nephropathy remains controversial. The authors resequenced the gene in 100 patients with IgA nephropathy and 100 controls, tested its linkage disequilibrium pattern, constructed haplotypes, and performed association and functional studies. First, the association between TRAC variants and IgA nephropathy was tested in 704 patients ...

  6. Ways of Treating IgA Nephropathies

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    Wardle E

    2000-01-01

    Full Text Available Summary: Treatment options for IgA nephropathy (IgAN must take into consideration the pathophysiology, namely the role of eicosanoids, angiotensin II and monocyte-macrophages releasing reactive oxygen species (ROS. Angiotensin converting enzyme inhibitors and early corticosteroid usage are prime therapies. Tonsillectomy should be considered. Other components of a therapeutic cocktail could be; (a thromboxane antogonist, (b leukotriene antagonist, (c platelet activating factor antagonist, (d an anti-oxidant and (e an anti-fibrotic agent like pentoxyfylline. In the new millenium, there will be focus on anti-proliferative measures like platelets dependent growth factor aptamers. For unusual cases with rapid progression, the use of FK-506 or mycophenolate mofetil can be considered.

  7. Canine IgA nephropathy: a case report.

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    Yabuki, Akira; Shimokawa Miyama, Takako; Kohyama, Moeko; Yamato, Osamu

    2016-04-01

    Immunoglobulin (Ig) A nephropathy is a rare form of canine glomerular disease. This report describes a case of canine IgA nephropathy showing characteristics typical of human IgA nephropathy. An 8-year-old, spayed female Miniature Dachshund showed persistent severe proteinuria without azotemia. She was receiving long-term glucocorticoid therapy due to chronic gastritis and an intra-abdominal suture granuloma. A renal biopsy demonstrated mesangial proliferative glomerulonephritis with predominantly mesangial IgA deposition and electron-dense deposits in the paramesangium. These findings closely resembled those of human IgA nephropathy. Glucocorticoid treatment was discontinued, and the angiotensin-converting enzyme inhibitor enalapril was administrated as an antiproteinuric agent. The proteinuria subsequently went into remission, and the patient has maintained good condition without recurrence. PMID:26596464

  8. IGA NEPHROPATHY IN A PATIENT WITH SYSTEMIC LUPUS ERITAMATOSUS

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    Karakose, Suleyman; Unverdi, Selman; Algul, Durak; Ensari, Arzu; Koc, Eyup; Duranay, Murat

    2014-01-01

    INTROduCTION. Autoimmune disorders might develop under the effect of various genetic, immunological, hormonal or environmental factors and they could involve a single organ or multiple organs and tissues. Systemic lupus erythematosus is a multisystem autoimmune disease with kidney involvement. IgA nephropathy is an uncommon cause of proteinuria in lupus nephritis. In the case presented here, IgA nephropathy was observed in the renal biopsy of a patient with SLE. CASE. During investigation of ...

  9. IgA on the surface of erythrocytes from IgA nephropathy patients

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    Matsuda, S.; Czerkinsky, C.; Moldoveanu, Z.; Mestecky, J.

    1986-03-05

    Erythrocytes (RBCs) have been reported to play a role in the transport of both IgG and IgA immune complexes in primates. Therefore they investigated the IgA on the surface of RBCs from IgA nephropathy (IgA NP) patients. Surface immunoglobulins were detected by radioimmunoassay using radiolabeled monoclonal anti-IgA1, anti-IgA2 and protein A. The RBCs from one-third of IgA NP patients examined had over 10 ng IgA1/4 x 10/sup 8/ RBCs, which was more than on RBCs from normal individuals. There was no surface IgA2 and the level of IgG on their surfaces was the same as that of normal RBCs. IgA1 present on patients' RBCs was displaced from the surface by incubation with monoclonal IgA1, but not with IgG, IgA2, IgM or C3. Furthermore, incubation with factor I (C3b inactivator) did not affect the binding of IgA1 on RBCs. Polyethylene glycol precipitates from the sera of IgA NP patients, which contained IgA1, IgG and C3, were able to bind to the RBCs from an IgA deficient patient. This binding was also inhibited by IgA1, but not IgG, IgA2, IgM or C3. These results suggest that the RBCs from IgA NP patients have IgA1 or IgA1 immune complexes on their surface and that the binding is mediated through the interaction of IgA1 and an IgA receptor on the surface of RBCs.

  10. Early pre-eclampsia unmasks underlying IgA nephropathy

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    Mona Singh

    2010-12-01

    Full Text Available Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on results of a renal biopsy. The biopsy noted the presence of both pre-eclampsia and immunoglobulin A (IgA nephropathy. Thus, the onset of pre-eclampsia unmasked the presence of unrecognized IgA nephropathy, and the IgA nephropathy was a risk factor for this patient developing pre-eclampsia. The results of a renal biopsy are key in distinguishing pre-eclampsia from other kidney diseases and instituting appropriate clinical management.Keywords: proteinuria, IgA nephropathy, renal biopsy, pre-eclampsia

  11. Serum galactose-deficient IgA1 levels in children with IgA nephropathy

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    Jiang, Mengjie; Jiang, Xiaoyun; Rong, Liping; Xu, Yuanyuan; Chen, Lizhi; Qiu, Zeting; Mo, Ying

    2015-01-01

    Immunoglobulin A nephropathy (IgAN) is an immunopathologic diagnosis based on a renal biopsy, it is characterized by deposits of IgA-containing immune complexes in the mesangium. Adults with IgAN have a galactose-deficient IgA1 in the circulation and glomerular deposition. There are few studies on the glycosylation of serum IgA1 in children with IgAN. To measure the serum levels of galactose-deficient IgA1 in pediatric patients with IgAN, 72 biopsy-proven IgAN children were divided into 3 gro...

  12. Minimal change disease versus IgA nephropathy

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    IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interestingly, the acute viral flare was without a concomitant relapse of proteinuria. (author)

  13. Minimal change disease versus IgA nephropathy

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    Jabur Wael

    2009-01-01

    Full Text Available IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interes-tingly, the acute viral flare was without a concomitant relapse of proteinuria.

  14. The association of single nucleotide P-selectin gene polymorphism with IgA nephropathy

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    王朝晖

    2006-01-01

    Objective IgA nephropathy is one of the most com- mon form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin gene polymorphism and IgA nephropathy. Methods In this study,a comprehensive P-selectin gene sur-

  15. Nefropatia por IgA nas espondiloartrites IgA nephropathy in spondyloarthritis

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    Daniela Castelo Azevedo

    2011-02-01

    Full Text Available Pacientes com espondiloartrites poderiam ser mais acometidos pela nefropatia por IgA do que a população geral, havendo, possivelmente, um mecanismo etiopatogênico comum. O seguinte artigo relaciona quatro casos que exemplificam essa possível associaçãoSpondyloarthritis patients can be more frequently affected by IgA nephropathy than the general population, and a common etiopathogenic mechanism can be involved. We report four cases that may exemplify that association

  16. Markers for the progression of IgA nephropathy.

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    Maixnerova, Dita; Reily, Colin; Bian, Qi; Neprasova, Michaela; Novak, Jan; Tesar, Vladimir

    2016-08-01

    We have summarized the latest findings on markers for progression of immunoglobulin A (IgA) nephropathy (IgAN), the most common primary glomerulonephritis with a high prevalence among end-stage renal disease (ESRD) patients. The clinical predictors of renal outcome in IgAN nephropathy, such as proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR) at the time of the diagnosis, are well known. The Oxford classification of IgAN identified four types of histological lesions (known as the MEST score) associated with the development of ESRD and/or a 50 % reduction in eGFR. In addition, the role of genetic risk factors associated with IgAN is being elucidated by genome-wide association studies, with multiple risk alleles described. Recently, biomarkers in serum (galactose-deficient IgA1, IgA/IgG autoantibodies against galactose-deficient IgA1, and soluble CD 89-IgA complexes) and urine (soluble transferrin receptor, interleukin-6/epidermal growth factor ratio, fractalkine, laminin G-like 3 peptide, κ light chains, and mannan-binding lectin) have been identified. Some of these biomarkers may represent candidates for the development of noninvasive diagnostic tests, that would be useful for detection of subclinical disease activity, monitoring disease progression, assessment of treatment, and at the same time circumventing the complications associated with renal biopsies. These advances, along with future disease-specific therapy, will be helpful in improving the treatment effectiveness, prognosis, and the quality of life in connection with IgAN. PMID:27142988

  17. Serum galactose-deficient IgA1 levels in children with IgA nephropathy.

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    Jiang, Mengjie; Jiang, Xiaoyun; Rong, Liping; Xu, Yuanyuan; Chen, Lizhi; Qiu, Zeting; Mo, Ying

    2015-01-01

    Immunoglobulin A nephropathy (IgAN) is an immunopathologic diagnosis based on a renal biopsy, it is characterized by deposits of IgA-containing immune complexes in the mesangium. Adults with IgAN have a galactose-deficient IgA1 in the circulation and glomerular deposition. There are few studies on the glycosylation of serum IgA1 in children with IgAN. To measure the serum levels of galactose-deficient IgA1 in pediatric patients with IgAN, 72 biopsy-proven IgAN children were divided into 3 groups based on the clinical features: isolated hematuria group (24 patients), hematuria and proteinuria group (22 patients), and nephritic syndrome group (26 patients). They were also divided into 3 groups according to pathologic grading: grade I + II group (25 patients), grade III group (33 patients) and grade IV + V group (14 patients). 30 healthy children were recruited as a control group. We used vicia villosa lectin binding enzyme-linked immunosorbent assay to measure the serum levels of galactose-deficient IgA1 in all groups and controls. Serum levels of galactose-deficient IgA1 in children with IgAN were higher than controls (P vicia villosa lectin binding enzyme-linked immunosorbent assay has a certain clinical value in diagnosis of children with IgAN. PMID:26221341

  18. IgA Nephropathy: New Aspects in Pathophysiology and Pathogenesis

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    Francois Berthoux

    2015-07-01

    Full Text Available Knowledge of the pathophysiology of immunoglobulin A nephropathy (IgAN has progressed significantly, with this disease being clearly identified as an autoimmune disease with a peculiar autoantigen (galactosedeficient IgA1 [Gd-IgA1], specific autoantibodies (IgG and IgA1 anti-glycans, and formation followed by mesangial deposition of circulating immune complexes with the involvement of other players, such as mesangial transferrin receptor (TfR, monocyte Fcα receptor (CD89, and glomerular transglutaminase 2 (TG2. The pathogenesis still requires additional clarifications in order to explain the initiation of the disease and to establish the respective role of genetics, environment, and hazard concordance in the cascade of events/steps. The clinical application of this new knowledge is spreading slowly and includes possible measurement of serum Gd-IgA1, IgG anti-Gd-IgA1, IgA anti-Gd-IgA1, soluble CD89, and soluble TfR in the urine of patients with IgAN.

  19. Gene Expression Analysis in Tubule Interstitial Compartments Reveals Candidate Agents for IgA Nephropathy

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    Jinling Wang

    2014-09-01

    Full Text Available Background/Aims: Our aim was to explore the molecular mechanism underlying development of IgA nephropathy and discover candidate agents for IgA nephropathy. Methods: The differentially expressed genes (DEGs between patients with IgA nephropathy and normal controls were identified by the data of GSE35488 downloaded from GEO (Gene Expression Omnibus database. The co-expressed gene pairs among DEGs were screened to construct the gene-gene interaction network. Gene Ontology (GO enrichment analysis was performed to analyze the functions of DEGs. The biologically active small molecules capable of targeting IgA nephropathy were identified using the Connectivity Map (cMap database. Results: A total of 55 genes involved in response to organic substance, transcription factor activity and response to steroid hormone stimulus were identified to be differentially expressed in IgA nephropathy patients compared to healthy individuals. A network with 45 co-expressed gene pairs was constructed. DEGs in the network were significantly enriched in response to organic substance. Additionally, a group of small molecules were identified, such as doxorubicin and thapsigargin. Conclusion: Our work provided a systematic insight in understanding the mechanism of IgA nephropathy. Small molecules such as thapsigargin might be potential candidate agents for the treatment of IgA nephropathy.

  20. Treatment of progressive IgA nephropathy: an update.

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    Wang, Weiming; Chen, Nan

    2013-01-01

    IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. About 25-30% of IgAN patients will progress to end-stage kidney disease in 20-25 years. Early-onset symptoms that are highly suggestive of progressive IgAN include massive proteinuria, hypertension, renal damage, glomerular sclerosis, crescent formation, and tubulointerstitial fibrosis. Progressive IgAN may progress to renal failure in a short time. Optimized supportive therapy is the fundamental treatment for progressive IgAN patients, and includes renin-angiotensin system blockers, blood pressure control, antiplatelet and anticoagulant drugs, statins, and allopurinol. In progressive IgAN patients whose clinical and pathological manifestations are more severe, active therapy may be considered including glucocorticoid therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, and other immunosuppressants. However, there are currently controversies on the definition and treatment of progressive IgAN. PMID:23689569

  1. Treatment of IgA nephropathy with renal insufficiency.

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    Pozzi, Claudio; Sarcina, Cristina; Ferrario, Francesca

    2016-08-01

    IgA Nephropathy leads young people to dialysis more often than other glomerular diseases, because often diagnosis and therapy are made late. Nephrologists waive to treat IgAN pts with chronic renal insufficiency, believing that treatment may not be effective and safe. Moreover, studies in IgAN pts with reduced renal function are lacking. Small studies seem to indicate a possible utility of RAS blockers and corticosteroids in these patients. Recently, VALIGA study showed that corticosteroids and immunosuppressants were more frequently used in pts with eGFR 30 ml/min (60 vs. 44 %, respectively; p = 0.004). The goal of treating IgAN pts is to obtain a time-average proteinuria 1 g/day a 6-month course of corticosteroids could be useful and safe. PMID:26743078

  2. IgA Nephropathy in a Patient Presenting with Pseudotumor Cerebri

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    Umair Syed Ahmed

    2016-01-01

    Full Text Available IgA nephropathy is the most common glomerulonephritis worldwide and typically has minimal signs for chronicity in histopathology at the time of initial presentation. Pseudotumor cerebri (PTC is characterized by increased intracranial pressure in the absence of any intracranial lesions, inflammation, or obstruction. PTC has been reported in renal transplant and dialysis patients, but we are unaware of any reports of pseudotumor cerebri in patients with IgA nephropathy. We report a case of a young female who presented with signs and symptoms of pseudotumor cerebri and was subsequently diagnosed with IgA nephropathy and end-stage renal disease. To our knowledge this is the first report of IgA nephropathy presenting as end-stage renal disease in a patient who presented with pseudotumor cerebri.

  3. IgA Nephropathy in a Patient Presenting with Pseudotumor Cerebri

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    Ahmed, Umair Syed; Bacaj, Patrick; Iqbal, Hafiz Imran; Onder, Songul

    2016-01-01

    IgA nephropathy is the most common glomerulonephritis worldwide and typically has minimal signs for chronicity in histopathology at the time of initial presentation. Pseudotumor cerebri (PTC) is characterized by increased intracranial pressure in the absence of any intracranial lesions, inflammation, or obstruction. PTC has been reported in renal transplant and dialysis patients, but we are unaware of any reports of pseudotumor cerebri in patients with IgA nephropathy. We report a case of a young female who presented with signs and symptoms of pseudotumor cerebri and was subsequently diagnosed with IgA nephropathy and end-stage renal disease. To our knowledge this is the first report of IgA nephropathy presenting as end-stage renal disease in a patient who presented with pseudotumor cerebri. PMID:26989531

  4. Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

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    Mototsugu Tanaka

    2011-01-01

    Full Text Available Predominant or codominant immunoglobulin (Ig A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN. Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

  5. Presence of circulating macromolecular IgA in patients with hematuria due to primary IgA nephropathy

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    Valentijn, R.M.; Kauffmann, R.H.; de la Riviere, G.B.; Daha, M.R.; Van, E.S.

    1983-03-01

    The relation between renal histologic features and the presence of circulating immune complexes was studied in 50 patients with hematuria. Primary IgA nephropathy was found in 25 patients, and various other forms of glomerulopathy were seen in the remaining 25 patients. Circulating immune complexes were detected with the 125I-C1q-binding assay, the conglutinin-binding assay, and the anti-IgA inhibition binding assay, the latter detecting specifically IgA-containing immune complex-like material. The 125I-C1q-binding assay gave negative findings for all patients except one. With the conglutinin-binding assay, immune complexes were found in a similar frequency for patients with and without IgA nephropathy. However, the anti-IgA inhibition binding assay gave positive results only in patients with primary IgA nephropathy (68 percent) and in none of the other patients. Sucrose density ultracentrifugation, as well as experiments in which the anti-IgA inhibition binding assay was performed with and without pretreatment of serum with polyethylene glycol, showed the presumed IgA immune complexes to have intermediate sedimentation coefficients (11 to 21S). The presence and level of this macromolecular IgA in the circulation correlated significantly (p less than 0.001) with the presence of hematuria in patients who had this clinical manifestation intermittently. Furthermore, a significant correlation (r . 0.69, p less than 0.0001) was found between the degree of hematuria and the degree of positive findings of the anti-IgA inhibition binding assay. This study shows that in patients presenting with hematuria, a positive finding on the anti-IgA inhibition binding assay is restricted to patients with primary IgA nephropathy and therefore could be of diagnostic value.

  6. O-glycosylation of serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy.

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    Smith, Alice C; Molyneux, Karen; Feehally, John; Barratt, Jonathan

    2006-12-01

    In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation deposits in the glomerular mesangium. The underlying mechanism of this IgA1 O-glycosylation abnormality is poorly understood, but recent evidence argues against a generic defect in B cell glycosyltransferases, suggesting that only a subpopulation of IgA1-committed B cells are affected. For investigation of whether the site of antigen encounter influences IgA1 O-glycosylation, the O-glycosylation of serum IgA1 antibodies against a systemic antigen, tetanus toxoid (TT), and a mucosal antigen, Helicobacter pylori (HP), was studied in patients with IgAN and control subjects. Serum IgA1 was purified from cohorts of patients with IgAN and control subjects with HP infection and after systemic TT immunization. The IgA1 samples were applied to HP- and TT-coated immunoplates to immobilize specific antibodies, and IgA1 O-glycosylation profiles were assessed by binding of the O-glycan-specific lectin Vicia villosa using a modified ELISA technique. Although total serum IgA1 had raised lectin binding in IgAN, the O-glycosylation of the specific IgA1 antibodies to TT and HP did not differ between patients and control subjects. In both groups, IgA1 anti-HP had higher lectin binding than IgA1 anti-TT. This study demonstrates that IgA1 O-glycosylation normally varies in different immune responses and that patients produce the full spectrum of IgA1 O-glycoforms. IgA1 with high lectin binding was produced in response to mucosal HP infection in all subjects. The raised circulating level of this type of IgA1 in IgAN is likely to be a consequence of abnormal systemic responses to mucosally encountered antigens rather than a fundamental defect in B cell O-glycosylation pathways. PMID:17093066

  7. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy.

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    Jingjing Zhou

    Full Text Available BACKGROUND: Uromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy. METHODS: A total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0. RESULTS: We found that lower baseline urinary uromodulin levels (P = 0.03 and higher time-average proteinuria (P = 0.04 were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016. Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02. CONCLUSIONS: Urinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

  8. IgA nephropathy in Brazil: apropos of 600 cases.

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    Soares, Maria Fernanda; Caldas, M L R; Dos-Santos, W L C; Sementilli, A; Furtado, P; Araújo, S; Pegas, K L; Petterle, R R; Franco, M F

    2015-01-01

    IgA nephropathy (IgAN) is th e commonest primary glomerular disease worldwide. Studies on its prevalence in Brazil are however scarce. Databases and clinical records from 10 reference centres were retrospectively reviewed. Clinical and laboratory features at the moment of the biopsy were retrieved (age, gender, presence of hematuria, serum creatinine [mg/dL], proteinuria [g/24 h]). Renal biopsy findings were classified according to Haas single grade classification scheme and the Oxford Classification of IgAN. 600 cases of IgAN were identified, of which 568 (94.7 %) were on native kidneys. Male to female ratio was 1.24:1. Patients averaged 32.76 ± 15.12 years old (range 4-89, median 32). Proteinuria and hematuria were observed, respectively in 56.63 and 72.29 % of patients. The association of both these findings occurred in 37.95 % of the cases. Serum creatinine averaged 1.65 ± 0.67 mg/dL (median 1.5 mg/dL) at diagnosis. Segmental sclerosis and mesangial hypercellularity were the main glomerular findings (47.6 and 46.2 %) The commonest combination by Oxford Classification of IgAN, was M0 E0 S0 T0 (22.4 %). Chronic tubulo-interstitial lesions with an extension wider than 25 % of the renal cortex could be identified in 32.2 % of the cases. Tubular atrophy and interstitial fibrosis were more strongly associated with higher 24-h proteinuria and serum creatinine levels. Segmental sclerosis (S1) showed a stronger tendency of association with the presence of tubulo-interstitial lesions (T1 and T2) than other glomerular variables. To the best of our knowledge this is the largest series of IgAN in Brazil. It depicts the main biopsy findings and their possible clinical correlates. Our set of data is comparable to previous reports. PMID:26435893

  9. The coincidence of IgA nephropathy and Fabry disease

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    Maixnerová Dita

    2013-01-01

    Full Text Available Abstract Background IgA nephropathy (IgAN is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD. Case presentation A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient’s plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted. The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Conclusions Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic

  10. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

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    Sina Moeller

    Full Text Available IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99, unaffected controls of similar age, gender, and race (n = 96, and patients with biopsy-proven celiac disease (n = 30. All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2. Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  11. Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.

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    Masashi Aizawa

    Full Text Available Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN, at least in part, are localized in bone marrow (BM. Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6. Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.

  12. Silicosis and renal disease: insights from a case of IgA nephropathy.

    Science.gov (United States)

    Riccò, Matteo; Thai, Elena; Cella, Simone

    2016-01-01

    A 68-yr-old male, smoker, is admitted for proteinuria (2,800 mg/24 h) and reduced renal function (serum creatinine 2 mg/dl, GFR 35 ml/min). Renter, he started working 20-yr-old as a sandstone cave miner. Despite the high levels of silica dusts, he reported no mandatory use of airways protection devices during the first 25 yr of activity. No clinical or radiological signs of silicosis or pneumoconiosis where reported until the year of retirement (1997). Erythrocyte sedimentation rate (91 mm/h) and C reactive protein (35 mg/l) suggested a pro-inflammatory status. High serum IgA was found (465 mg/dl). A renal biopsy identified glomerular sclerosis with IgA deposition, signs of diffuse vasculitis and tubular atrophia suggesting a diagnosis of IgA nephropathy. Chest X-Rays showed emphysema and diffuse nodularity suggesting diagnosis of silicosis. Chest tomography was also positive for mild signs of silicosis with silicotic nodules and without honeycombing. IgA nephropathy is the most common type of glomerulonephritis worldwide. Several clues suggest a genetic or acquired abnormality of immune system as a trigger of the increased production of IgA. In our case report, simultaneous kidney and pulmonary disease could suggest same triggers (e.g. exposure to virus, bacteria or environmental agents) inducing IgA synthesis and pulmonary immune system activation. PMID:26423329

  13. Iga nephropathy-its seasonal variation and clinico pathological profile in local patients

    International Nuclear Information System (INIS)

    To study the frequency of IgA nephropathy in relation to seasonal variation and its clinico-pathological profile at Military Hospital Rawalpindi. Study Design: A descriptive study. Place and Duration of Study: Military Hospital, Rawalpindi, Pakistan from Jan 2010 to Mar 2012 Patients and Methods: The study was conducted at Military Hospital Rawalpindi on 289 consecutive renal biopsy specimens. Ultrasound guided percutaneous renal biopsies were carried out in patients with the following findings: 1) Proteinuria > 1000 mg/day in adults, 2) Isolated glomerular haematuria with proteinuri a 500-1000 mg/day, 3) Proteinuria < 500 mg/day with impaired renal functions, 4) Steroid resistant nephrotic syndrome in children. Light microscopy after Haematoxylin and Eosin, PAS and Silver stains was employed for diagnosis on formaline fixed tissue, while diagnosis of IgA nephropathy was established upon findings of characteristic IgA deposits on immunofluorescence studies on a separate core of unfixed tissue. Results: A total of 289 renal biopsies were performed, out of which 45 were diagnosed with IgA nephropathy indicating a frequency of 15.5 %.The most common mode of clinical presentation was asymptomatic microscopic haematuria with proteinuria 500-1000 mg per day in 14 patients (31%). The most common histopathological finding was mesangial proliferation and hypercellularity in 15 biopsies (43%). Deposition of IgA with IgM and C3 complement was the most frequent finding on immunofluorescence in 37 biopsies (82.2%). About 80% of patients with IgA nephropathy presented in relatively colder months starting from Jan -Mar and from Sep-Dec. Conclusion: IgA nephropathy is one of the most frequent diagnoses on renal biopsies. It usually presents in young male adults in the age range of 21-30 years with most common clinical presentation being asymptomatic microscopic haematuria. The most common pathological finding was mesangial proliferation and hypercellularity with deposition of IgA

  14. Cellular Signaling and Production of Galactose-Deficient IgA1 in IgA Nephropathy, an Autoimmune Disease

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    Colin Reily

    2014-01-01

    Full Text Available Immunoglobulin A (IgA nephropathy (IgAN, the leading cause of primary glomerulonephritis, is characterized by IgA1-containing immunodeposits in the glomeruli. IgAN is a chronic disease, with up to 40% of patients progressing to end-stage renal disease, with no disease-specific treatment. Multiple studies of the origin of the glomerular immunodeposits have linked elevated circulating levels of aberrantly glycosylated IgA1 (galactose-deficient in some O-glycans; Gd-IgA1 with formation of nephritogenic Gd-IgA1-containing immune complexes. Gd-IgA1 is recognized as an autoantigen in susceptible individuals by anti-glycan autoantibodies, resulting in immune complexes that may ultimately deposit in the kidney and induce glomerular injury. Genetic studies have revealed that an elevated level of Gd-IgA1 in the circulation of IgAN patients is a hereditable trait. Moreover, recent genome-wide association studies have identified several immunity-related loci that associated with IgAN. Production of Gd-IgA1 by IgA1-secreting cells of IgAN patients has been attributed to abnormal expression and activity of several key glycosyltransferases. Substantial evidence is emerging that abnormal signaling in IgA1-producing cells is related to the production of Gd-IgA1. As Gd-IgA1 is the key autoantigen in IgAN, understanding the genetic, biochemical, and environmental aspects of the abnormal signaling in IgA1-producing cells will provide insight into possible targets for future disease-specific therapy.

  15. Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

    DEFF Research Database (Denmark)

    Stuchlová Horynová, Milada; Raška, Milan; Clausen, Henrik;

    2013-01-01

    Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O...

  16. The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

    Science.gov (United States)

    Knoppova, Barbora; Reily, Colin; Maillard, Nicolas; Rizk, Dana V.; Moldoveanu, Zina; Mestecky, Jiri; Raska, Milan; Renfrow, Matthew B.; Julian, Bruce A.; Novak, Jan

    2016-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgAN is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or codominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O-glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgAN as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by antiglycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgAN have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgAN varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified several loci associated with IgAN. Some of these loci are associated

  17. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.

    Science.gov (United States)

    da Silva, Leonardo Sales; Almeida, Bruna Laiza Fontes; de Melo, Ana Karla Guedes; de Brito, Danielle Christine Soares Egypto; Braz, Alessandra Sousa; Freire, Eutília Andrade Medeiros

    2016-01-01

    Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms. PMID:27267646

  18. IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

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    Leonardo Sales da Silva

    2016-06-01

    Full Text Available Abstract Systemic erythematosus lupus (SLE is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN, the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

  19. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

    Science.gov (United States)

    McQuarrie, Emily P; Mackinnon, Bruce; McNeice, Valerie; Fox, Jonathan G; Geddes, Colin C

    2014-01-01

    Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy. PMID:24025641

  20. IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia

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    Khawajah Azhar

    2010-01-01

    Full Text Available A total of 42 patients, who were diagnosed to have primary Immunoglobulin A neph-ropathy (IgAN at the King Abdul Aziz University Hospital and King Faisal Hospital, Jeddah over the last seven years, were studied. The objective was to analyze their clinical and pathological fea-tures and to classify them according to Hass Classification by using light, immunofluorescence and electron microscopy. Majority of the study cases were males in the second, third and fourth decades of life. Hematuria was the most common clinical complaint followed by proteinuria. There were varying degrees of mesangial proliferation. Majority of the cases presented with class-2 followed by class-3. Immunofluorescence demonstrated diffuse granular deposition of IgA in the glomerular mesangium in majority of the cases. Ultrastructural analysis showed electron dense deposits within the matrix of the mesangium and paramesangium in majority of the cases. Sub-endothelial deposits and mesangial interposition were demonstrated in few cases. Extensive effacement with fusion of the visceral epithelial foot processes was detected in only few patients while focal effacement was demonstrated in many cases. Irregularities of the glomerular basement membrane were seen in some cases. We conclude that IgA nephropathy is an immune-complex glomerular disease, which occurs at all ages and with higher frequency in males and presents mostly with hematuria and proteinuria. Public health awareness is seriously needed to perform the investigations at an early stage.

  1. Identification of distinct glycoforms of IgA1 in plasma from patients with IgA nephropathy and healthy individuals

    DEFF Research Database (Denmark)

    Lehoux, Sylvain; Mi, Rongjuan; Aryal, Rajindra P;

    2014-01-01

    Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis worldwide and is histologically characterized by the deposition of IgA1 and consequent inflammation in the glomerular mesangium. Prior studies suggested that serum IgA1 from IgAN patients contains aberrant...... different glycoforms of IgA1 in plasma from patients with IgAN and healthy individuals. While total plasma IgA in IgAN patients was elevated ~1.6-fold compared to that in healthy donors, IgA1 in all samples was unexpectedly separable into two distinct glycoforms: one with core 1 based O-glycans, and the...... other exclusively containing Tn/STn structures. Importantly, Tn antigen present on IgA1 from IgAN patients and controls was convertible into the core 1 structure in vitro by recombinant T-synthase. Our results demonstrate that undergalactosylation of O-glycans in IgA1 is not restricted to IgAN and...

  2. Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy

    DEFF Research Database (Denmark)

    Renfrow, MB; Mackay, CL; Chalmers, MJ;

    2007-01-01

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis. In IgAN, IgA1 molecules with incompletely galactosylated O-linked glycans in the hinge region (HR) are present in mesangial immunodeposits and in circulating immune complexes. It is not known whether the galactose...... deficiency in IgA1 proteins occurs randomly or preferentially at specific sites. We have previously demonstrated the first direct localization of multiple O-glycosylation sites on a single IgA1 myeloma protein by use of activated ion-electron capture dissociation (AI-ECD) Fourier transform ion cyclotron...... resonance (FT-ICR) tandem mass spectrometry. Here, we report the analysis of IgA1 O-glycan heterogeneity by use of FT-ICR MS and liquid chromatography FT-ICR MS to obtain unbiased accurate mass profiles of IgA1 HR glycopeptides from three different IgA1 myeloma proteins. Additionally, we report the first AI...

  3. Pathological Role of Tonsillar B Cells in IgA Nephropathy

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    Yusuke Suzuki

    2011-01-01

    Full Text Available Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.

  4. Central MHC genes affect IgA levels in the human: reciprocal effects in IgA deficiency and IgA nephropathy.

    Science.gov (United States)

    Matthews, Vance B; Witt, Campbell S; French, Martyn A H; Machulla, Helmut K G; De la Concha, Emilio G; Cheong, Karey Y; Vigil, Patricia; Hollingsworth, Peter N; Warr, Kevin J; Christiansen, Frank T; Price, Patricia

    2002-05-01

    This study investigates the hypothesis that alternative alleles of one or more genes in the central major histocompatibility complex (MHC) predispose carriers to IgA deficiency (IgAD) or IgA Nephropathy (IgAN). Australian caucasian IgAD, IgAN patients, and controls were typed at HLA loci, single nucleotide polymorphisms, and microsatellites in the MHC. Alleles of the D6S273 microsatellite exhibited strong associations with IgAD and IgAN. D6S273*129 and *139 were more frequent in IgAD and less frequent in IgAN patients than controls. The reverse was true for D6S273*133 and *131. Alleles of other microsatellites exhibited weak associations with IgAD or IgAN. D6S273*129 is found on the 65.1 ancestral haplotype [HLA-B14(65),DR1], which has been reported to be increased in IgAD, but the majority of IgAD patients with D6S273*129 did not have other alleles of the haplotype. D6S273*139 is characteristic of the 8.1 ancestral haplotype (HLA-A1,B8,DR3), which was common in IgAD and rare in IgAN patients. Further studies of the 8.1 haplotype in Australian, German and Spanish caucasian subjects revealed that HLA-DR3, in the absence of -B8, is not associated with IgAD. However -B8 is associated with IgAD in the absence of -DR3, consistent with a susceptibility locus in the central MHC. Provisional mapping within this region is discussed. PMID:11975987

  5. Analysis of renal dynamic imaging with radionuclide in patients with different IgA nephropathies

    International Nuclear Information System (INIS)

    Objective: To explore the value of renal dynamic imaging with radionuclide in patients with different IgA nephropathies (IgAN). Methods: Seventy cases of IgAN determined by nephrocentesis were divided into 4 groups according to their pathologic classification. The glomerular filtration rate (GFR) and radionuclide clearance at 20 min (C20) were measured and the differences of functional parameters among the groups were compared. Results: The GFR was concordant with the serum creatinine (SCr) and blood urea nitrogen (BUN), and changed earlier than the increase of BUN and SCr in renal failure. GFR is a reliable index of renal filtration function. Moreover, the reduced C20 association with severe pathologic changes was observed, especially in patients with interstitial lesions. Conclusion: The renal dynamic imaging with 99Tcm-DTPA is of important value in assessing the renal function and the prognosis in patients with IgAN

  6. IgA Nephropathy and Henoch-Schoenlein Purpura Nephritis: Aberrant Glycosylation of IgA1, Formation of IgA1-Containing Immune Complexes, and Activation of Mesangial Cells

    DEFF Research Database (Denmark)

    Novak, J.; Moldoveanu, Z.; Renfrow, M.B.;

    2007-01-01

    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy...... exposes N-acetylgalactosamine-containing neoepitopes recognized by naturally occurring IgG or IgA1 antibodies resulting in formation of immune complexes. IgA1 contains up to six O-glycosylation sites per heavy chain; it is not known whether the glycosylation defect occurs randomly or preferentially at...... specific sites. We sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma protein and analyze the formation of the immune complexes and their biological activities. Supplementation of serum or cord-blood serum with this IgA1 protein resulted in formation of new IgA1 complexes...

  7. Case Report: Rare occurrence of Pseudomonas aeruginosa osteomyelitis of the right clavicle in a patient with IgA nephropathy

    OpenAIRE

    Damodaran, Aishwarya; Rohit, Anusha; Abraham, Georgi; Nair, Sanjeev; Yuvaraj, Anand; Prasad, Kashi Nath; Dakshinamurthy, K. V.

    2014-01-01

    We describe the case of a 47 year old patient with proven primary IgA nephropathy who presented with osteomyelitis of the medial end of the right clavicle. The patient was not on immunosuppressive medications. He underwent aspiration curettage and CT scan of the clavicle which yielded pus that grew Pseudomonas aeruginosa. Following treatment with appropriate antibiotic therapy the patient presented a complete recovery of the lesion with no loss of renal function. This case highlights the impo...

  8. Validation of the Oxford classification of IgA nephropathy for pediatric patients from China

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    Le Weibo

    2012-11-01

    Full Text Available Abstract Background The Oxford classification of IgA nephropathy (IgAN provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations. Methods A total of 218 children with IgAN from 7 renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study. Results There were 98 patients (45% with mesangial proliferation (M1, 51 patients (23% with endocapillary proliferation (E1, 136 patients (62% with segmental sclerosis/adhesion lesion (S1, 13 patients (6% with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred, and only 2 patients (1% with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred. During a median follow-up duration of 56 months, 24 children (12.4% developed ESRD or 50% decline in renal function. In univariate COX analysis, we found that tubular atrophy/interstitial fibrosis (HR 4.3, 95%CI 1.8-10.5, P  Conclusions We confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN.

  9. IgA Nephropathy: A Twenty Year Retrospective Single Center Experience

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    Jacob Rube

    2009-01-01

    Full Text Available IgA nephropathy (IgAN is a common glomerular disease whose etiology is unknown. Previous studies have described the clinical and laboratory features but none have specifically compared patients during different time periods. This 20 year retrospective study was performed to assess trends in the severity of IgAN from 1989–2008. We reviewed 57 patient charts that contained a confirmed biopsy diagnosis of IgAN and recorded data at the time of diagnosis and the final follow-up appointment. Clinical data included physical examination, urine, and blood tests. Patients were separated into two cohorts, Cohort 1 1989–1998 and Cohort 2 1999–2008. An increase in severity was noted in Cohort 2 based on a significantly higher Up/c and lower serum albumin level. Other prognostic indicators including GFRe, hematocrit, and glomerular injury score also demonstrated a trend towards more severe disease over the past 20 years. The patients in both Cohorts received similar treatments and had comparable renal function at the last follow-up visit. Based on our findings, we suggest that although a kidney biopsy is required to diagnose IgAN, the procedure may not be necessary in patients clinically suspected of having the disease but who have normal kidney function and minimal urine abnormalities.

  10. Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

    Science.gov (United States)

    Ring, Troels; Pedersen, Birgitte Bang; Salkus, Giedrius; Goodship, Timothy H.J.

    2015-01-01

    IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement. PMID:26413271

  11. NF-kB Expression in IgA Nephropathy Outcome

    Science.gov (United States)

    Silva, G. E. B.; Costa, R. S.; Ravinal, R. C.; Ramalho, L. Z.; dos Reis, M. A.; Coimbra, T. M.; Dantas, M.

    2011-01-01

    Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB) in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1) to analyze the prognostic value of NF-kB expression in primary IgA nephropathy (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell tryptase and polyclonal antibodies to TGF-β1, α-SMA and NF-kB p65. We used SWH for the in situ detection of activated NF-kB. The results showed that NF-kB expression (mainly by SWH) correlated with clinical and histological parameters. An unfavorable clinical course of IgAN was significantly related to tubular NF-kB expression by SWH, but not by IHC. The Kaplan-Meier curves demonstrated that increased NF-kB expression, which was measured by IHC and SWH, decreased renal survival. In conclusion, the increased expression of NF-kB in the tubular area may be a predictive factor for the poor prognosis of patients with IgAN. Compared with IHC, NF-kB expression determined by SWH was correlated with a larger number of parameters of poor disease outcome. PMID:21846944

  12. Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Tokunaga, Koki [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Uto, Hirofumi, E-mail: hirouto@m2.kufm.kagoshima-u.ac.jp [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan); Takami, Yoichiro; Mera, Kumiko; Nishida, Chika; Yoshimine, Yozo; Fukumoto, Mayumi; Oku, Manei; Sogabe, Atsushi; Nosaki, Tsuyoshi; Moriuchi, Akihiro; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito [Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2010-08-20

    Research highlights: {yields} IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. {yields} Serum IGFBP-1 levels are high in patients with IgA nephropathy. {yields} Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.

  13. Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

    International Nuclear Information System (INIS)

    Research highlights: → IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. → Serum IGFBP-1 levels are high in patients with IgA nephropathy. → Serum IGFBP-1 levels correlate with renal function and the severity of renal injury. -- Abstract: The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.

  14. Profiling and initial validation of urinary microRNAs as biomarkers in IgA nephropathy

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    Nannan Wang

    2015-06-01

    Full Text Available Background. MicroRNAs (miRNAs have been found in virtually all body fluids and used successfully as biomarkers for various diseases. Evidence indicates that miRNAs have important roles in IgA nephropathy (IgAN, a major cause of renal failure. In this study, we looked for differentially expressed miRNAs in IgAN and further evaluated the correlations between candidate miRNAs and the severity of IgAN. Methods. Microarray and RT-qRCR (real-time quantitative polymerase chain reaction were sequentially used to screen and further verify miRNA expression profiles in urinary sediments of IgAN patients in two independent cohorts. The screening cohort consisted of 32 urine samples from 18 patients with IgAN, 4 patients with MN (membranous nephropathy, 4 patients with MCD (minimal changes disease and 6 healthy subjects; the validation cohort consisted of 102 IgAN patients, 41 MN patients, 27 MCD patients and 34 healthy subjects. The renal pathological lesions of patients with IgAN were evaluated according to Lee’s grading system and Oxford classification. Results. At the screening phase, significance analysis of microarrays analysis showed that no miRNA was differentially expressed in the IgAN group compared to all control groups. But IgAN grade I–II and III subgroups (according to Lee’s grading system shared dysregulation of two miRNAs (miR-3613-3p and miR-4668-5p. At the validation phase, RT-qPCR results showed that urinary level of miR-3613-3p was significantly lower in IgAN than that in MN, MCD and healthy controls (0.47, 0.44 and 0.24 folds, respectively, all P < 0.01 by Mann–Whitney U test; urinary level of miR-4668-5p was also significantly lower in IgAN than that in healthy controls (0.49 fold, P < 0.01. Significant correlations were found between urinary levels of miR-3613-3p with 24-hour urinary protein excretion (Spearman r = 0.50, P = 0.034, eGFR (estimated glomerular filtration rate (r = − 0.48, P = 0.043 and Lee’s grades (r = 0

  15. Race/ethnicity and disease severity in IgA nephropathy

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    Chertow Glenn M

    2004-09-01

    Full Text Available Abstract Background Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN, and that the severity of disease is increased in these populations. Methods To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system. Results Among individuals with IgAN (N = 149, 89 (60% were male, 57 (38% white, 53 (36% Asian/Pacific Islander, 29 (19% Hispanic, 4 (3% African American and 6 (4% were of other or unknown ethnicity. The mean age was 37 ± 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44% exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8% cases were classified into Haas subclass I, 12 (10% subclass II, 23 (18% subclass III, 30 (25% subclass IV, and 49 (40% subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149, 77 (52% patients were male, 51 (34% white, 42 (28% Asian/Pacific Islander, 25 (17% Hispanic, and 30 (20% were African American. Conclusions With the caveats of referral and biopsy biases, the race

  16. Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-xi; ZHOU Jun-fu; SHEN Han-chao

    2005-01-01

    Objective: To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies. Methods: Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric mothods. Results: Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P<0.0001), while those ofVC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P<0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those ofVC, VE, β-CAR,SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P<0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, β-CAR, SOD, CAT and GPX were decreased gradually (P<0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the Ig

  17. Predicting progression of IgA nephropathy: new clinical progression risk score.

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    Jingyuan Xie

    Full Text Available IgA nephropathy (IgAN is a common cause of end-stage renal disease (ESRD in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HR = 0.96(0.95-0.97], serum albumin [HR = 0.47(0.32-0.68], hemoglobin [HR = 0.79(0.72-0.88], and SBP [HR = 1.02(1.00-1.03]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification.

  18. Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

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    Gyl Eanes Barros Silva

    2012-07-01

    Full Text Available OBJECTIVES: The objectives of our study were as follows: 1 to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN and 2 to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB. METHODS: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB. RESULTS: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry. In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course. CONCLUSION: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

  19. The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.

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    Jeffrey B Hodgin

    Full Text Available IgA nephropathy (IgAN is a clinically and pathologically heterogeneous disease. Endocapillary proliferation is associated with higher risk of progressive disease, and clinical studies suggest that corticosteroids mitigate this risk. However, corticosteroids are associated with protean cellular effects and significant toxicity. Furthermore the precise mechanism by which they modulate kidney injury in IgAN is not well delineated. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system independently by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation compared to IgAN without endocapillary lesions. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways that can be impacted by corticosteroids. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for the treatment of IgAN, including resveratrol and hydroquinine. In summary, we have defined the distinct molecular profile of a pathologic phenotype associated with progressive renal insufficiency in IgAN. Exploration of the pathways associated with endocapillary proliferation confirms a molecular basis for the clinical effectiveness of corticosteroids in this subgroup of IgAN, and elucidates new therapeutic strategies for IgAN.

  20. Elevated Plasma α-Defensins (HNP1-3) Levels Correlated with IgA1 Glycosylation and Susceptibility to IgA Nephropathy.

    Science.gov (United States)

    Qi, Yuan-Yuan; Zhou, Xu-Jie; Cheng, Fa-Juan; Zhang, Hong

    2016-01-01

    Aim. IgA nephropathy (IgAN) is the most common form of glomerulonephritis. Recent genome-wide association study (GWAS) suggested that DEFA locus (which encodes α-defensins) may play a key role in IgAN. Methods. The levels of α-defensins in 169 IgAN patients and 83 healthy controls were tested by ELISA. Results. We observed that α-defensins human neutrophil peptides 1-3 (HNP1-3) in IgAN patients were elevated compared with healthy controls. The mean levels of α-defensins of 83 healthy controls and 169 IgAN patients were 50 ng/mL and 78.42 ng/mL. When the results were adjusted to the mean levels of α-defensins of IgAN patients, the percentage of individuals with high levels of α-defensins increased in IgAN patients (22.5%) compared to healthy controls (9.6%) (p = 0.013). The elevation of α-defensins in IgAN patients was independent of renal function or neutrophil count, which were major sources of α-defensins in circulation. More importantly, negative correlation was observed between galactose-deficient IgA1and α-defensins. Conclusion. As α-defensin is a lectin-like peptide, we speculated that it might be involved in IgA galactose deficiency. The data implied that patients with IgAN had higher plasma α-defensins levels and high α-defensins correlated with IgA galactose deficiency, further suggesting a pathogenic role of α-defensins in IgAN. PMID:27563166

  1. Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling

    OpenAIRE

    Graterol, Fredzzia; Navarro-Muñoz, Maribel; Ibernon, Meritxell; López, Dolores; Troya, Maria-Isabel; Pérez, Vanessa; Bonet, Josep; Romero, Ramón

    2013-01-01

    Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification. Methods We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjec...

  2. Case Report: Rare occurrence of Pseudomonas aeruginosa osteomyelitis of the right clavicle in a patient with IgA nephropathy

    Science.gov (United States)

    Damodaran, Aishwarya; Rohit, Anusha; Abraham, Georgi; Nair, Sanjeev; Yuvaraj, Anand

    2014-01-01

    We describe the case of a 47 year old patient with proven primary IgA nephropathy who presented with osteomyelitis of the medial end of the right clavicle. The patient was not on immunosuppressive medications. He underwent aspiration curettage and CT scan of the clavicle which yielded pus that grew Pseudomonas aeruginosa. Following treatment with appropriate antibiotic therapy the patient presented a complete recovery of the lesion with no loss of renal function. This case highlights the importance of positive cultures in the choice of the appropriate therapy in an extremely rare case of an immunocompetent patient with osteomyelitis of the clavicle. PMID:25566352

  3. Collapsing glomerulopathy following anabolic steroid use in a 16-year-old boy with IgA nephropathy

    OpenAIRE

    Matthai, S. M.; Basu, G.; Varughese, S.; Pulimood, A. B.; Veerasamy, T.; Korula, A.

    2015-01-01

    Collapsing glomerulopathy (CG) is a proliferative podocytopathy, increasingly recognized in a variety of disease conditions. We report a case of CG in a 16-year-old boy with IgA nephropathy (IgAN) who presented with acute kidney injury, marked proteinuria and hypertension following a short period of anabolic steroid use. Although CG has been associated with long-term anabolic steroid use among body builders, there is no data on the effect of anabolic steroid use in persons with underlying ren...

  4. Decreased Circulating C3 Levels and Mesangial C3 Deposition Predict Renal Outcome in Patients with IgA Nephropathy

    OpenAIRE

    Seung Jun Kim; Hyang Mo Koo; Beom Jin Lim; Hyung Jung Oh; Dong Eun Yoo; Dong Ho Shin; Mi Jung Lee; Fa Mee Doh; Jung Tak Park; Tae-Hyun Yoo; Shin-Wook Kang; Kyu Hun Choi; Hyeon Joo Jeong; Seung Hyeok Han

    2012-01-01

    BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled betw...

  5. Clinical-pathologic significance of CD163 positive macrophage in IgA nephropathy patients with crescents

    OpenAIRE

    Li, Jun; Liu, Chang-hua; Gao, Bo; Xu, Dao-Liang

    2015-01-01

    Background: CD163, a marker of M2 macrophages, express anti-inflammatory properties. This study aims to investigate the difference of CD163 positive macrophages expression between IgA nephropathy patients with and without crescents. Methods: Renal tissues from IgAN patients (n = 24), including IgAN with crescents (n = 10), IgAN without crescents (n = 14), minimal change disease (MCD, as disease control, n = 8) and normal control kidneys (negative control, n = 3), were included in this study. ...

  6. Mortality of IgA nephropathy patients: a single center experience over 30 years.

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    Hajeong Lee

    Full Text Available Research on the prognosis of IgA nephropathy (IgAN has focused on renal survival, with little information being available on patient survival. Hence, this investigation aimed to explore long-term patient outcome in IgAN patients. Clinical and pathological characteristics at the time of renal biopsy were reviewed in 1,364 IgAN patients from 1979 to 2008. The outcomes were patient death and end stage renal disease (ESRD progression. Overall, 71 deaths (5.3% and 277 cases of ESRD (20.6% occurred during 13,916 person-years. Ten-, 20-, and 30-year patient survival rates were 96.3%, 91.8%, and 82.7%, respectively. More than 50% patient deaths occurred without ESRD progression. Overall mortality was elevated by 43% from an age/sex-matched general population (GP (standardized mortality ratio [SMR], 1.43; 95% confidence interval [CI], 1.04-1.92. Men had comparable mortality to GP (SMR, 1.22; 95% CI, 0.82-1.75, but, in women, the mortality rate was double (SMR, 2.17; 95% CI, 1.21-3.57. Patients with renal risk factors such as initial renal dysfunction (estimated glomerular filgration rate <60 ml/min per 1.73 m(2; SMR, 1.70; 95% CI, 1.13-2.46, systolic blood pressure ≥ 140 mmHg (SMR, 1.88; 95% CI, 1.19-2.82 or proteinuria ≥ 1 g/day (SMR, 1.66; 95% CI, 1.16-2.29 had an elevated mortality rate. Patients with preserved renal function, normotension, and proteinuria <1 g/day, however, had a similar mortality rate to GP. When risk stratification was performed by counting the number of major risk factors present at diagnosis, low-risk IgAN patients had a mortality rate equal to that of GP, whereas high-risk patients had a mortality rate higher than that of GP. This investigation demonstrated that overall mortality in IgAN patients was higher than that of GP. Women and patients with renal risk factors had a higher mortality than that of GP, Therefore, strategies optimized to alleviate major renal risk factors are warranted to reduce patient mortality.

  7. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

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    Yasuyuki Nagasawa

    Full Text Available BACKGROUND: Immunoglobulin (IgA nephropathy (IgAN is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. METHODS AND FINDINGS: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062. Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012. Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002. Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019. There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046, and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037 by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. CONCLUSION: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  8. Oxford classification of IgA nephropathy is applicable to predict long-term outcomes of Henoch-Schönlein purpura nephritis.

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    Hamid Nasri

    2014-12-01

    Full Text Available Henoch-Schönlein purpura nephritis and IgA nephropathy are currently considered to be different clinical presentations of the same disease. There is need for a reliable proven, morphologic classification that can help clinicians more accurately formulate treatment strategies for patients with Henoch-Schönlein purpura nephritis. Considering that Henoch-Schönlein purpura nephritis and IgA nephropathy have common characteristics of pathogenesis and histopathologic findings, we postulate that, the Oxford classification could also help predict long-term outcomes in Henoch-Schönlein purpura nephritis. Hence, we suggest to applicate the Oxford classification for patients with Henoch-Schönlein purpura nephritis.

  9. Increased plasma sVCAM-1 is associated with severity in IgA nephropathy

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    Zhu Li

    2013-01-01

    Full Text Available Abstract Background A considerable proportion of IgAN patients present with histological vasculitic/crescentic lesions in glomeruli, indicating activation of vascular inflammation. Using sVCAM-1, a well-proven marker for endothelial injury under inflammatory processes, we investigated vascular injury and its association with clinical and pathological manifestations in IgAN patients. Methods In this study, 327 biopsy-proven IgAN patients and 55 healthy controls were enrolled. The Oxford classification and two variables, Active Crescentic Lesion Percentage (ACLP and Chronic Glomerular Lesion Percentage (CGLP, were used for evaluating pathological lesions. Human Umbilical Vein Endothelial Cells were treated with 25-400 ug/ml IgA1. sVCAM-1 in plasma and culture supernatant were measured by ELISA. Results Plasma sVCAM-1 in IgAN patients was significantly higher than healthy controls. In patients with IgAN, plasma sVCAM-1 was significantly correlated with eGFR, 24h urine protein excretion, tubular atrophy/interstitial fibrosis lesion and ACLP, but not CGLP. Meanwhile, compared to healthy volunteers, IgA1 from IgAN patients showed a tendency to increase the HUVECs supernatant sVCAM-1 expression. And IgA1 induced the sVCAM-1 increasing from HUVECs in time- and dose-dependent manner. Conclusions We found increased plasma sVCAM-1 in IgAN patients and its association with severe clinical and pathological manifestations, which might be partly resulted from effect of IgA1 to endothelial cells.

  10. Effect of erythropoietin loading chitosan-tripolyphosphate nanoparticles on an IgA nephropathy rat model

    OpenAIRE

    Zhang, Xiaoli; Wu, Yin; Sun, Kun; Tan, Jing

    2014-01-01

    The aim of the present study was to investigate the effect of erythropoietin (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine (Cr) levels were measured in ea...

  11. The risk of recurrent IgA nephropathy in a steroid-free protocol and other modifying immunosuppression.

    Science.gov (United States)

    Von Visger, J R; Gunay, Y; Andreoni, K A; Bhatt, U Y; Nori, U S; Pesavento, T E; Elkhammas, E A; Winters, H A; Nadasdy, T; Singh, N

    2014-08-01

    Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post-kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid-based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid-free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow-up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid-free (HR 8.59: 3.03, 24.38, p drugs in reducing recurrence of IgAN and other glomerulonephritis post-transplant. PMID:24869763

  12. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

    Science.gov (United States)

    Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Del Vecchio, Lucia; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Battaglia, Giovanni Giorgio; Garozzo, Maurizio; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; Pączek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J; Novak, Jan; Julian, Bruce A; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P; Gharavi, Ali G

    2014-11-01

    We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

  13. Corticotherapy response in primary IgA nephropathy Resposta à corticoterapia na nefropatia da IgA primária

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    Natália Novaretti

    2013-03-01

    Full Text Available INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group. The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h and was 703 mg/24h (245; 983 and 684 mg/24h (266; 1023 at the 6th (p INTRODUÇÃO: Tem sido sugerido que tratamento mais prolongado com corticosteroides pode ser benéfico em pacientes com nefropatia da IgA primária. OBJETIVO: Neste estudo retrospectivo avaliamos os efeitos na proteinúria e na função renal após 12 meses do protocolo baseado no uso por 6 meses de corticosteroides. MÉTODO: Doze pacientes receberam pulsos de 1 g/dia de metilprednisolona intravenosa por 3 dias consecutivos no início dos meses 1, 3 e 5, seguidos por prednisona (0,5 mg/kg por via oral em dias alternados após cada pulso durante 6 meses (grupo tratado. O grupo controle foi composto por nove pacientes não tratados. RESULTADOS: A proteinúria (mg/24h; mediana; 25º; 75º percentis no período basal no grupo tratado foi de 1861 (1518; 2417 e de 703 (245; 983 e de 684 (266; 1023 nos 6º (p < 0,05 vs. basal e 12º (p < 0,05 vs. basal meses, respectivamente. No grupo controle, a proteinúria foi de 1900 (1620; 3197 no período basal e de 2290 (1500; 2975 e de 1600 (1180; 2395 nos 6º e 12º meses, respectivamente (não significantes vs. basal. Comparado com o grupo controle, o grupo tratado teve menor proteinúria (p < 0,05 e número maior de pacientes em remissão (p < 0,05 nos 6º

  14. The Akt/mTOR/p70S6K pathway is activated in IgA nephropathy and rapamycin may represent a viable treatment option.

    Science.gov (United States)

    Tian, Jihua; Wang, Yanhong; Guo, Haixiu; Li, Rongshan

    2015-12-01

    IgA nephropathy (IgAN) is one of the most frequent forms of glomerulonephritis, and 20 to 40% of patients progress to end-stage renal disease (ESRD) within 20 years of disease onset. However, little is known about the molecular pathways involved in the altered physiology of mesangial cells during IgAN progression. This study was designed to explore the role of mTOR signaling and the potential of targeted rapamycin therapy in a rat model of IgAN. After establishing an IgA nephropathy model, the rats were randomly divided into four groups: control, control+rapamycin, IgAN and IgA+rapamycin. Western blotting and immunohistochemistry were performed to determine phospho-Akt, p70S6K and S6 protein levels. Coomassie Brilliant Blue was utilized to measure 24-h urinary protein levels. The biochemical parameters of the rats were analyzed with an autoanalyzer. To evaluate IgA deposition in the glomeruli, FITC-conjugated goat anti-rat IgA antibody was used for direct immunofluorescence. Cellular proliferation and the mesangial matrix in glomeruli were assayed via histological and morphometric procedures. Our results showed that p70S6K, S6 and Akt phosphorylation were significantly upregulated in IgAN rats, and rapamycin effectively inhibited p70S6K and S6 phosphorylation. A low dose of the mTOR inhibitor rapamycin reduced proteinuria, inhibited IgA deposition, and protected kidney function in an IgAN rat model. Low-dose rapamycin treatment corresponded to significantly lower cellular proliferation rates and a decreased mesangial matrix in the glomeruli. In conclusion, the Akt/mTOR/p70S6K pathway was activated in IgAN, and our findings suggested that rapamycin may represent a viable option for the treatment of IgAN. PMID:26297427

  15. Research progress of microRNA in IgA nephropathy%microRNA在IgA肾病发病机制中的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙嫱; 沈颖

    2014-01-01

    IgA肾病发病机制复杂,病因不明,一些microRNA可能参与其致病过程,并且可能与其关键酶——核心β1、3半乳糖基转移酶相关.现介绍表观遗传学的定义,microRNA的概念、基本结构和功能.结合文献总结、概述目前在IgA肾病患者中已经发现的异常表达的microRNA,以及其可能的作用方式.%IgA nephropathy is a complex disease with unclear mechanism,microRNAs may involve in the disease,and some of them may be associated with the key enzyme of IgA nephropathy-core β1 3-galactosyl-transferase.The concept of epigenetics and the structures and functions of microRNA were introduced.Through reviewing the related researches,several microRNAs expressing abnormally in IgA nephropathy was found.

  16. Association of glomerular C4d deposition with various demographic data in IgA nephropathy patients; a preliminary study

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    Nasri, Hamid; Ahmadi, Ali; Rafieian-kopaei, Mahmood; Bashardoust, Bahman; Nasri, Parto; Mubarak, Muhammed

    2015-01-01

    Background: IgA nephropathy (IgAN) is the most prevalent primary chronic glomerulopathy worldwide. Thus, it is of vital importance to search for factors aggravating the disease progress, monitor disease activity and predict disease-specific therapy. C4d is a well-known biomarker of the complement cascade with a potential to meet the above needs. Objectives: The aim of our study was, therefore, to determine whether C4d staining at the time of kidney biopsy had any correlation with the demographic, clinical and biochemical variables in IgAN. Patients and Methods: The definition of IgAN requires the presence of diffuse and global IgA deposits which were graded ≥2+ and weak C1q deposition. C4d immunohistochemical staining was conducted retrospectively on 29 renal biopsies of patients with IgAN, which were selected randomly from all biopsies. C4d immunohistochemical staining was performed on 3-μm deparaffinized and rehydrated sections of formaldehyde-fixed, paraffin-embedded renal tissues. Results: Of 29 selected patients, 68% were male. In this study, 54.2±25 percent of glomeruli in all biopsies were positive for C4d. The mean and standard deviation (SD) of serum creatinine and the magnitude of proteinuria were 1.72±1.2 mg/dl and 1582±1214 mg/day, respectively. In this study, we observed statistically significant correlations of percent C4d positivity with the serum creatinine (r=0.61, p=0.0005), magnitude of proteinuria (r=0.72, p=0.0001), the proportion of globally sclerotic glomeruli (r=0.43, p=0.02) and the proportion of tubulointerstitial fibrosis (r=0.54, p=0.0023). Conclusions: The results from our investigation on C4d positivity in biopsy-proven cases of IgAN are in accord with some of the previous studies. These findings, however, require further validation in larger samples. PMID:25657981

  17. Circulating TNF receptors 1 and 2 are associated with the severity of renal interstitial fibrosis in IgA nephropathy.

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    Yuji Sonoda

    Full Text Available The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2 in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN. The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9. Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1] and negatively correlated with estimated glomerular filtration rate (eGFR. Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.

  18. Circulating TNF receptors 1 and 2 are associated with the severity of renal interstitial fibrosis in IgA nephropathy.

    Science.gov (United States)

    Sonoda, Yuji; Gohda, Tomohito; Suzuki, Yusuke; Omote, Keisuke; Ishizaka, Masanori; Matsuoka, Joe; Tomino, Yasuhiko

    2015-01-01

    The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN). The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR) and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with estimated glomerular filtration rate (eGFR). Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear. PMID:25860248

  19. Dual involvement of growth arrest-specific gene 6 in the early phase of human IgA nephropathy.

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    Kojiro Nagai

    Full Text Available BACKGROUND: Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN. METHODS: The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. RESULTS: In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. CONCLUSIONS: Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.

  20. Circulating Tumor Necrosis Factor α Receptors Predict the Outcomes of Human IgA Nephropathy: A Prospective Cohort Study.

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    Yun Jung Oh

    Full Text Available The circulating tumor necrosis factor receptors (TNFRs could predict the long-term renal outcome in diabetes, but the role of circulating TNFRs in other chronic kidney disease has not been reported. Here, we investigated the correlation between circulating TNFRs and renal histologic findings on kidney biopsy in IgA nephropathy (IgAN and assessed the notion that the circulating TNFRs could predict the clinical outcome. 347 consecutive biopsy-proven IgAN patients between 2006 and 2012 were prospectively enrolled. Concentrations of circulating TNFRs were measured using serum samples stored at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; ≥ 30% decline compared to baseline. Mean eGFR decreased and proteinuria worsened proportionally as circulating TNFR1 and TNFR2 increased (P < 0.001. Tubulointerstitial lesions such as interstitial fibrosis and tubular atrophy were significantly more severe as concentrations of circulating TNFRs increased, regardless of eGFR levels. The risks of reaching the primary endpoint were significantly higher in the highest quartile of TNFRs compared with other quartiles by the Cox proportional hazards model (TNFR1; hazard ratio 7.48, P < 0.001, TNFR2; hazard ratio 2.51, P = 0.021. In stratified analysis according to initial renal function classified by the eGFR levels of 60 mL/min/1.73 m2, TNFR1 and TNFR2 were significant predictors of renal progression in both subgroups. In conclusion, circulating TNFRs reflect the histology and clinical severity of IgAN. Moreover, elevated concentrations of circulating TNFRs at baseline are early biomarkers for subsequent renal progression in IgAN patients.

  1. Differential glomerular immunoexpression of matrix metalloproteinases MMP-2 and MMP-9 in idiopathic IgA nephropathy and Schoenlein-Henoch nephritis.

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    Małgorzata Wagrowska-Danilewicz; Marian Danilewicz

    2010-01-01

    Both idiopathic IgA nephropathy (IgAN) and Schoenlein-Henoch nephritis (SHN) are characterized by cell proliferation and abnormal extracellular matrix (ECM) remodeling by mesangial cells leading to fibrosis, sclerosis and end-stage renal disease. Matrix metalloproteinases MMP-2 and MMP-9 are reported as the most important proteolytic enzymes involved in remodeling of ECM. Therefore, the aim of the present study was to determine glomerular immunoexpression of MMP-2 and MMP-9 in IgAN and SHN. A...

  2. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy.

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    Seung Jun Kim

    Full Text Available BACKGROUND AND AIMS: Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN. However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. METHODS: A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3 was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD and a doubling of the baseline serum creatinine (D-SCr. RESULTS: Of the patients, there were 66 patients (19.2% with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6% with hypoC3 compared with 9 patients (3.2% with normal C3 levels (P = 0.11. However, 12 patients (18.2% with hypoC3 reached D-SCr compared with 17 patients (6.1% with normal C3 levels [Hazard ratio (HR, 3.59; 95% confidence interval (CI, 1.33-10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92-0.99; P = 0.011. The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10-80.26; P = 0.04. CONCLUSIONS: This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.

  3. The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

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    Alexopoulos Efstathios

    2005-12-01

    Full Text Available Abstract Background IgA nephropathy (IgAN or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. Description The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: http://www.igan.net. The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents, 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5th Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: http://www.cordis.lu/marketplace. Conclusion The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained

  4. IgA Nephropathy

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... immune system lower a person’s blood cholesterol levels Control Blood Pressure and Slow Progression of Kidney Disease ...

  5. IgA Nephropathy

    Science.gov (United States)

    ... 24-hour albumin excretion. A patient may have chronic kidney disease if the urine albumin-to-creatinine ratio is ... a local anesthetic. The health care provider uses imaging techniques such as ... diagnose diseases––examines the kidney tissue with a microscope. Only ...

  6. The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China

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    Lu Huan

    2016-05-01

    Full Text Available OBJECTIVE: This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001 was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria ‘thresholds’ of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin

  7. Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA Nephropathy in Adults from a Chinese Han Population.

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    Bin Yang

    Full Text Available MicroRNA 146a (miR-146a is a 19 to 23 nucleotide long, small non-coding RNA with gene regulatory functions that has influence on the pathogenesis of many diseases. A single nucleotide polymorphism (rs2910164 C>G in pre-miR-146a is correlated with the expression of miR-146a. The aim of this study was to perform an association analysis of rs2910164 with IgA nephropathy in adult patients from a Chinese Han population.A total of 145 patients with renal biopsy-proved IgA nephropathy (IgAN and 179 healthy controls were recruited to the current study. rs2910164 was genotyped by the polymerase chain reaction (PCR and high-resolution melting methods (HRM. Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of kidney biopsy.There were significant differences among the population of patients grouped by different age of onset in a co-dominant model (CG vs. CC vs. GG (p = 0.033 and a recessive model (CG+CC vs. GG (p = 0.001. However, no significant difference was observed in the distribution of genotypes between cases and controls (p = 0.144. There was also no significant difference between rs2910164 and patient quantitative traits (all p > 0.003 or different pathology grading (Lee's grading system and tubular atrophy/interstitial fibrosis in the Oxford classification (all p > 0.05.There was no association of rs2910164 with susceptibility to IgAN in adults from a Chinese Han population. However, rs2910164 was correlated with the age of onset of IgAN in adult patients.

  8. Synergistic effect of mesangial cell-induced CXCL1 and TGF-β1 in promoting podocyte loss in IgA nephropathy.

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    Li Zhu

    Full Text Available Podocyte loss has been reported to relate to disease severity and progression in IgA nephropathy (IgAN. However, the underlying mechanism for its role in IgAN remain unclear. Recent evidence has shown that IgA1 complexes from patients with IgAN could activate mesangial cells to induce soluble mediator excretion, and further injure podocytes through mesangial-podocytic cross-talk. In the present study, we explored the underlying mechanism of mesangial cell-induced podocyte loss in IgAN. We found that IgA1 complexes from IgAN patients significantly up-regulated the expression of CXCL1 and TGF-β1 in mesangial cells compared with healthy controls. Significantly higher urinary levels of CXCL1 and TGF-β1 were also observed in patients with IgAN compared to healthy controls. Moreover, IgAN patients with higher urinary CXCL1 and TGF-β1 presented with severe clinical and pathological manifestations, including higher 24-hour urine protein excretion, lower eGFR and higher cresentic glomeruli proportion. Further in vitro experiments showed that increased podocyte death and reduced podocyte adhesion were induced by mesangial cell conditional medium from IgAN (IgAN-HMCM, as well as rhCXCL1 together with rhTGF-β1. In addition, the over-expression of CXCR2, the receptor for CXCL1, by podocytes was induced by IgAN-HMCM and rhTGF-β1, but not by rhCXCL1. Furthermore, the effect of increased podocyte death and reduced podocyte adhesion induced by IgAN-HMCM and rhCXCL1 and rhTGF-β1 was rescued partially by a blocking antibody against CXCR2. Moreover, we observed the expression of CXCR2 in urine exfoliated podocytes in IgAN patients. Our present study implied that IgA1 complexes from IgAN patients could up-regulate the secretion of CXCL1 and TGF-β1 in mesangial cells. Additionally, the synergistic effect of CXCL1 and TGF-β1 further induced podocyte death and adhesion dysfunction in podocytes via CXCR2. This might be a potential mechanism for podocyte loss

  9. Immuno-morphological aspects of the pathogenesis iga-nephropathy in patients with adenovirus infection with regard to age

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    I. A. Rakityanskaya

    2014-09-01

    Full Text Available In recent years, examines the role of viral infection in the development of IgA-nephropathy. In our study, an analysis of renal biopsy tissue from 17 patients IgA-nephropathy in the presence of adenoviral antigen. Shown the presence of adenovirus infection in kidney tissue in patients with IgA-nephropathy, regardless of age: 52% of patients 60 years and 33% of patients older than 60 years. Revealed that the presence of adenovirus in the glomerular zone of influence on the severity of global sclerosis in both age groups (p <0.05 and in patients younger than 60 years the presence of adenovirus in the interstitium correlated with the severity of degeneration of the epithelium of tubules (p = 0.014. It also shows that the presence of adenovirus in the interstitium correlated with cell phenotype CD19 / λ (p = 0,004 and CD19 / κ (p = 0,002, intenstivnostyu expression of IL-10 (p = 0,029 and membranoatakuyuschego complex S5b-C9 (p = 0.011 in the glomerular zone in patients younger than 60 years. In patients older than 60 years, the influence of adenoviral infection of renal tissue to a local immune response have been identified. Based on these results, it is concluded that the presence of adenovirus infection in the kidney plays a role in the pathogenesis of IgA-nephropathy

  10. Mesangial C3 deposition and decreased serum C3 levels in patients with IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    章晓炎

    2014-01-01

    Objective To explore the clinical significance of complement activation in Ig A nephropathy(IgAN)patients and provide new potential therapy targets.Methods Biopsy-proven IgAN patients admitted in our renal center were retrospectively recruited.Demographic,baseline clinical and pathological data were recorded as well as the follow-up results.Patients were divided into three groups,negative,weak positive and strong positive

  11. Case Report: Rare occurrence of Pseudomonas aeruginosa osteomyelitis of the right clavicle in a patient with IgA nephropathy [v1; ref status: indexed, http://f1000r.es/37r

    OpenAIRE

    Aishwarya Damodaran; Anusha Rohit; Georgi Abraham; Sanjeev Nair; Anand Yuvaraj

    2014-01-01

    We describe the case of a 47 year old patient with proven primary IgA nephropathy who presented with osteomyelitis of the medial end of the right clavicle. The patient was not on immunosuppressive medications. He underwent aspiration curettage and CT scan of the clavicle which yielded pus that grew Pseudomonas aeruginosa. Following treatment with appropriate antibiotic therapy the patient presented a complete recovery of the lesion with no loss of renal function. This case highlights the impo...

  12. Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome.

    Science.gov (United States)

    Yang, Shun-Min; Ka, Shuk-Man; Hua, Kuo-Feng; Wu, Tzu-Hua; Chuang, Yi-Ping; Lin, Ya-Wen; Yang, Feng-Ling; Wu, Shih-Hsiung; Yang, Sung-Sen; Lin, Shih-Hua; Chang, Jia-Ming; Chen, Ann

    2013-08-01

    High levels of reactive oxygen species (ROS), systemic T cell activation, and macrophage infiltration in the kidney are implicated in the acceleration and progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis. However, the pathogenic mechanism of IgAN is still little understood, and it remains a challenge to establish a specific therapeutic strategy for this type of glomerular disorder. Recently, we showed that antroquinonol (Antroq), a pure active compound from Antrodia camphorata mycelium, inhibits renal inflammation and reduces oxidative stress in a mouse model of renal fibrosis. But the anti-inflammatory and immune-regulatory effects of Antroq on the acceleration and progression of primary glomerular disorders have not been determined. In this study, we show that Antroq administration substantially impeded the development of severe renal lesions, such as intense glomerular proliferation, crescents, sclerosis, and periglomerular interstitial inflammation, in mice with induced accelerated and progressive IgAN (AcP-IgAN). Further mechanistic analysis in AcP-IgAN mice showed that, early in the developmental stage of the AcP-IgAN model, Antroq promoted the Nrf2 antioxidant pathway and inhibited the activation of T cells and NLRP3 inflammasome. Significantly improved proteinuria/renal function and histopathology in AcP-IgAN mice of an established stage supported potential therapeutic effects of Antroq on the disease. In addition, Antroq was shown to inhibit activation of NLRP3 inflammasome in vitro by an IgA immune complex (IC) partly involving a reduced ROS production in IgA-IC-primed macrophages, and this finding may be helpful in the understanding of the mode of action of Antroq in the treated AcP-IgAN mice. PMID:23567192

  13. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function

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    Onda Kisara

    2011-11-01

    Full Text Available Abstract Background Glomerular damage in IgA nephropathy (IgAN is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. Methods Membrane attack complex (MAC, properdin (P, factor H (fH and Complement receptor type 1 (CR1 were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens. Results Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p Conclusions Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.

  14. The role of Chlamydia Trachomatis in renal tissue in the pathogenesis IGA-nephropathy related to age

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    I. A. Rakityanskaya

    2014-09-01

    Full Text Available IgA-nephropathy is the most common form of primary glomerulonephritis in the world and therefore the mechanisms of this isease are actively explored. In our study, an analysis of renal biopsy issue from 117 patients IgA-nephropathy in the presence of Chlamydia trachomatis antigen related to age (before and after 60 years. It was shown that the presence of C. trachomatis in the glomerular zone influence on the severity of segmental sclerosis (p <0.05, and its presence in the interstitium affect on the size of the glomeruli (p <0.02 and severity of degeneration of epithelial tubules (p <0.02 regardless of patient age. It was shown the effect of C. trachomatis on the expression of local immune response of kidney tissue. In patients under 60 years: C. trachomatis in the glomeruli affects the number of cells of the phenotype CD25 (p = 0,04 and CD19 / κ (p = 0,034 in the glomerular infiltration and the presence of antigen in the interstitium affect the expression of CD95 (APO-1/Fas (p = 0,038 by mononuclear cells infiltration and formation of deposits S5b-C9 (p = 0,042 in the interstitial space. In patients older than 60 years of presence C. trachomatis in the glomerular zone impacts on the expression of TNF-α (p = 0,039 in the glomeruli, the presence of antigen in interstitium affect the number of cells CD71 (p = 0,025 in the interstitial infiltrate. Based on these results, we concluded that the presence of Chlamydia trachomatis antigen has an impact on the development and course of the disease and is the etiologic agent in patients with IgA-nephropathy, regardless of age.

  15. The Application of SILAC Mouse in Human Body Fluid Proteomics Analysis Reveals Protein Patterns Associated with IgA Nephropathy

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    Shilin Zhao

    2013-01-01

    Full Text Available Body fluid proteome is the most informative proteome from a medical viewpoint. But the lack of accurate quantitation method for complicated body fluid limited its application in disease research and biomarker discovery. To address this problem, we introduced a novel strategy, in which SILAC-labeled mouse serum was used as internal standard for human serum and urine proteome analysis. The SILAC-labeled mouse serum was mixed with human serum and urine, and multidimensional separation coupled with tandem mass spectrometry (IEF-LC-MS/MS analysis was performed. The shared peptides between two species were quantified by their SILAC pairs, and the human-only peptides were quantified by mouse peptides with coelution. The comparison for the results from two replicate experiments indicated the high repeatability of our strategy. Then the urine from Immunoglobulin A nephropathy patients treated and untreated was compared by this quantitation strategy. Fifty-three peptides were found to be significantly changed between two groups, including both known diagnostic markers for IgAN and novel candidates, such as Complement C3, Albumin, VDBP, ApoA,1 and IGFBP7. In conclusion, we have developed a practical and accurate quantitation strategy for comparison of complicated human body fluid proteome. The results from such strategy could provide potential disease-related biomarkers for evaluation of treatment.

  16. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway.

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    Kuo-Feng Hua

    Full Text Available Renal reactive oxygen species (ROS and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation of IgA nephropathy (IgAN, which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L. Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1 reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2 inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3 decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4 inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5 inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

  17. The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

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    Jiyun Yang

    2012-05-01

    Full Text Available Abstract Background Immunoglobulin A nephropathy (IgAN, an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition. Methods In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT in 291 IgAN cases and 420 matched controls. Results The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10-5, odds ratio (OR =1.381, 95% confidence interval (CI 1.178–1.619. Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects. Conclusion HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN.

  18. Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China.

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    Shui-Ming Guo

    Full Text Available Soluble urokinase receptor (suPAR may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN.We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed.We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001 and multivariate (P < 0.001 analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions.Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN.

  19. Baseline proteinuria, urinary osmotic pressure, and renal function as positive predictors of corticosteroids plus cyclophosphamide treatment efficacy in IgA nephropathy

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    Fang Jing; Li Wenge; Li Duo; Tan Zhao

    2014-01-01

    Background Very limited data are available on factors predictive of corticosteroids plus cyclophosphamide treatment efficacy on IgA nephropathy (IgAN).The aim of the study was to research the clinical factors predictive of treatment efficacy in IgAN.Methods One hundred and fifty-nine patients with IgAN (proteinuria ≥2 g/d and estimated glomerular filtration rate 30-89 ml·min-1·1.73 m-2) were treated with corticosteroids/cyclophosphamide followed by a 12-month follow-up.According to their response,these patients were divided into remission group (proteinuria <0.5 g/d) and non-remission group (proteinuria ≥0.5 g/d),and their clinical data collected.Results In the present study,72.96% of the individuals underwent a complete remission,and their response was related to baseline proteinuria,urinary osmotic pressure,and renal function (P <0.05).Patients with baseline proteinuria more than 3 g/d,urinary osmotic pressure greater than 600 mOsm/L,and eGFR 60-89 ml·min-1·1.73 m-2 responded well to the combination of corticosteroids and cyclophosphamide (86.90% vs.57.33%,P=0.000; 81.48% vs.64.10%,P=0.014; 83.17% vs.55.17%,P=0.000).Conclusion The response to the combination of corticosteroids and cyclophosphamide might be well associated with baseline proteinuria,urinary osmotic pressure,and renal function in patients with IgAN.

  20. Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study.

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    Yanhong Yuan

    Full Text Available Renal relapse is a very common manifestation of IgA nephropathy (IgAN. The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored.Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study.Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5% of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4% in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6% in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index and calibration curve. The results were validated using bootstrap resampling on the validation cohort.This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse.

  1. Case Report: Rare occurrence of Pseudomonas aeruginosa osteomyelitis of the right clavicle in a patient with IgA nephropathy [v1; ref status: indexed, http://f1000r.es/37r

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    Aishwarya Damodaran

    2014-11-01

    Full Text Available We describe the case of a 47 year old patient with proven primary IgA nephropathy who presented with osteomyelitis of the medial end of the right clavicle. The patient was not on immunosuppressive medications. He underwent aspiration curettage and CT scan of the clavicle which yielded pus that grew Pseudomonas aeruginosa. Following treatment with appropriate antibiotic therapy the patient presented a complete recovery of the lesion with no loss of renal function. This case highlights the importance of positive cultures in the choice of the appropriate therapy in an extremely rare case of an immunocompetent patient with osteomyelitis of the clavicle.

  2. Low Birth Weight and Risk of Progression to End Stage Renal Disease in IgA Nephropathy-A Retrospective Registry-Based Cohort Study.

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    Paschal Ruggajo

    Full Text Available Low Birth Weight (LBW is a surrogate for fetal undernutrition and is associated with impaired nephron development in utero. In this study, we investigate whether having been born LBW and/or small for gestational age (SGA predict progression to ESRD in IgA nephropathy (IgAN patients.Retrospective registry-based cohort study.The Medical Birth Registry has recorded all births since 1967 and the Norwegian Renal Registry has recorded all patients with ESRD since 1980. Based on data from the Norwegian Kidney Biopsy Registry we included all patients diagnosed with IgAN in Norway from 1988-2013. These registries were linked and we analysed risk of progression to ESRD associated with LBW (defined as birth weight less than the 10th percentile and/or SGA (defined as birth weight less than the 10th percentile for gestational week by Cox regression statistics.We included 471 patients, of whom 74 developed ESRD. As compared to patients without LBW, patients with LBW had a hazard ratio (HR of 2.0 (95% confidence interval 1.1-3.7 for the total cohort, 2.2 (1.1-4.4 for males and 1.3 (0.30-5.8 for females. Corresponding HRs for SGA were 2.2 (1.1-4.2, 2.7 (1.4-5.5 and 0.8 (0.10-5.9. Further analyses showed that as compared to patients with neither LBW nor SGA, patients with either SGA or LBW did not have significantly increased risks (HRs of 1.3-1.4 but patients who were both LBW and SGA had an increased risk (HR 3.2 (1.5-6.8.Mean duration of follow-up only 10 years and maximum age only 46 years.Among IgAN patients, LBW and/or SGA was associated with increased risk for progression to ESRD, the association was stronger in males.

  3. 乙酰肝素酶在原发性IgA肾病患者肾小球中的表达%Clinical Significance of Expression of Heparanase in Glomerulus of IgA Nephropathy

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    曹英杰; 陈晓岚; 范亚平; 杨红利

    2012-01-01

    目的:探讨IgA肾病患者肾小球中乙酰肝素酶(Hpa)表达的差异及其与临床相关指标的关系.方法:选择在本院行肾穿刺确诊为IgA肾病的患者78例,按照Lee氏Ⅰ~Ⅳ级分为4组,对照组采用肾癌患者肾切除标本中无癌细胞浸润的正常肾组织,比较各组患者的临床指标包括尿素氮、血清肌酐、24 h尿蛋白定量及尿C3、尿变形红细胞计数等,免疫组化法检测肾组织中Hpa的表达.结果:对照组肾小球内仅有极少量Hpa表达,4组IgA肾病患者肾小球内均有Hpa表达,均高于对照组(P<0.001).IgA肾病4组间肾小球内Hpa表达强度差异亦有统计学意义(P<0.001),且其表达的强度与24 h尿蛋白定量呈正相关(P<0.01),与血清肌酐、尿素氮、尿变形红细胞计数及尿C3水平无明显相关性(P>0.05).结论:Hpa的异常表达参与IgA肾病的病理损害与蛋白尿的形成,下调Hpa有益于IgA肾病的转归.%Objective: To explore the expression and clinical significance of heparanase in glomerulus of patients with IgA nephropathy and its relationship with clinical parameters. Methods: A total of 78 patients with IgA nephropathy diagnosed by biopsy were classified into 4 groups according to the Lees classification. Nephrectomy specimens of normal kidney tissues of renal carcinoma were used as the control group. Clinical parameters were detected in five groups of patients including urea nitrogen, serum creatinine, 24 h proteinuria, the third component of complement (C3) and urine red blood cells. The expression of heparanase in kidney was detected by immunohistochemistry. Results: There was very low expression of heparanase in glomerulus of control group. Compared with control group, expressions of heparanase were significantly increased in glomerulus of four IgA groups (P 0.05). Conclusion: The abnormal expressions of heparanase may correlate with the renal pathology and the development of proteinuria in patients with IgA

  4. Preliminary application of virtual touch tissue quantification imaging in diagnosis of IgA nephropathy%声触诊组织定量技术在系膜增生型IgA肾病诊断中的应用

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    梁晓宁; 郭瑞君; 李硕; 张颖; 张岩; 孙宏

    2015-01-01

    目的:探讨声触诊组织定量技术(VTQ)对系膜增生型IgA肾病的诊断价值。方法收集2013年12月至2014年7月在首都医科大学附属北京朝阳医院肾内科住院,被诊断为IgA肾病的患者85例,排除病情危重者、无法配合检查者、病理类型为非系膜细胞增生性IgA肾病者,最终入组54例系膜细胞增生型IgA肾病患者,108个肾脏。选取体检的健康志愿者54例,共计108个肾脏,作为健康对照组。使用VTQ技术分别测量健康对照组与系膜细胞增生型IgA肾病患者双肾中部肾实质及集合系统VTQ的SWV值,并进行比较。结果健康对照组双肾中部肾实质与集合系统的SWV值分别为(2.13±0.13)m/s、(1.15±0.02) m/s;IgA肾病组双肾中部肾实质与集合系统的SWV值分别为(3.07±0.62) m/s、(1.12±0.29) m/s。健康对照组肾实质与IgA肾病组肾实质SWV值比较,差异有统计学意义(t=-14.481,P0.05);健康对照组肾实质与集合系统SWV值比较,差异有统计学意义(t=-54.01,P<0.01);IgA肾病组肾实质与集合系统SWV值比较,差异有统计学意义(t=26.09,P<0.01)。伴随肾功能不全的加重,慢性肾病患者肾实质SWV值呈递增趋势(F=798.70, P<0.001)。叶间动脉阻力指数随慢性肾病1、2、3、4期逐渐增大。结论 VTQ技术对评价IgA肾病肾功能损害程度有一定诊断价值,为早期提示肾功能减低及判断其临床分期提供一个新的观察指标。%Objective To evaluate the value of virtual touch quantization (VTQ) imaging in diagnosis of IgA nephropathy. Methods The clinical data of 85 patients with IgA nephropathy were analyzed, who were treated in Capital Medical University Affiliate Beijing Chaoyang Hospital from December 2013 to July 2014. The patients who was with critical condition, unable to cooperate and with other pathological types were excluded. Finally 108 kidneys of IgA nephropathy with

  5. Elevated Levels of miR-146a and miR-155 in Kidney Biopsy and Urine from Patients with IgA Nephropathy

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    Gang Wang

    2011-01-01

    Full Text Available Background: Previous studies suggested miR-146a and miR-155 play important roles in innate and adaptive immune responses. We studied intra-renal and urinary levels of miR-146a and miR-155 in patients with immunoglobulin A nephropathy (IgAN.

  6. Factores moleculares implicados en el desarrollo de la nefropatía IgA en la población pediátrica / Molecular factors involved in the development of IgA nephropathy in the pediatric population

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    Pérez Morales, Rodrigo

    2011-01-01

    La nefropatía IgA, es una glomerulopatía primaria, de presentación habitual en la infancia, que puede conducir a falla renal terminal en un 25 a 30% de los casos, el problema radica, en que es una entidad que se diagnostica tarde debido al bajo índice de sospecha, a la necesidad de biopsia renal para su diagnóstico y que los síntomas son discretos, durante el curso de la enfermedad. Muchos aspectos de esta patología entre ellos: La clasificación histopatológica, la etiología...

  7. Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy

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    Alwin Tilanus

    2015-01-01

    Full Text Available We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic thrombocytopenic purpura (ITP and MPO-ANCA microscopic polyangiitis (MPA with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions.

  8. Serum and Urine Neutrophil Gelatinase-associated Lipocalin was related with clinical and pathological features in IgA nephropathy%血、尿NGAL与IgA肾病临床与病理的相关性研究

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    陈薪薪; 陈朝生; 陈宇; 吕吟秋; 陈波; 李凡凡; 陈孝倩; 许菲菲

    2013-01-01

    目的:探讨血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平与IgA肾病(IgAN)患者临床与病理表现的关系.方法:选择初次诊治经肾活检病理检查确诊为IgAN且未经激素或免疫抑制剂治疗的患者40例,同时选择10例健康体检者作为对照.收集临床和病理资料,应用酶联免疫吸附法(ELISA)检测血、尿NGAL水平,并分别用IgAN牛津分型和Katafuchi半定量标准对病理进行评分.分析血、尿NGAL与IgAN患者临床及病理指标的相关性.结果:血、尿NGAL反映IgAN肾功能情况较血肌酐(Scr)、血尿素氮(BUN)更敏感,与高血压、Scr、BUN、牛津分型的系膜增殖积分(M)、间质纤维化或小管萎缩(T)以及Katafuchi分型的系膜增殖、局灶节段病变、球性硬化、炎细胞浸润、间质纤维化、肾小管萎缩、血管壁增厚、小动脉玻变等多个指标相关性分析差异均有统计学意义(P0.6,P 0. 6, P < 0. 01 ). Receiver operating characteristic( ROC ) indicated that sNGAL and uNGAL were more sensitive than Scr and eGFR on reflecting the pathological damage in renal tubule and interstitium, while sNGAL was a more sensitive and specific than uNGAL. Conclusion: sNGAL and uNGAL were closely related with clinical and pathological features of IgA nephropathy. sNGAL and uNGAL were more sensitive and specific on reflecting the clinical and pathological lesions in IgAN , especially in renal tubule and interstitium. sNGAL and uNGAL could be sensitive markers to evaluate renal damage in IgA nephropathy.

  9. Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

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    Hernán Trimarchi

    2007-10-01

    Full Text Available Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 ± 13.26 years (50% male; 7 patients (35% were hypertensive; proteinuria 2.2 ± 1.86 g/day; serum creatinine 1.07 ± 0.29 mg/dl; mean follow-up 60.10 ± 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60% were class II; seven (35% were class III and one (5% class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 ± 0.07 g/day (P El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias >0.5 g/día y creatininas séricas <1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a <0.5 g

  10. 192例IgA肾病临床与牛津病理分型的分析%Analysis of the clinical characteristics and the Oxford classification of 192 cases of IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    马也娉; 李荣山; 王晨; 乔玉峰; 高丽芳

    2013-01-01

    目的 探讨IgA肾病患者的临床表现与牛津病理分型的相关性.方法 分析192例IgA肾病患者的临床表现(年龄、性别、病程、血压、血尿、24 h尿蛋白定量、血肌酐、血清白蛋白、甘油三酯、胆固醇、估计肾小球滤过率(eGFR))与病理资料(系膜细胞增生、内皮细胞增生、节段硬化或粘连、肾小管萎缩或间质纤维化、小动脉积分、细胞或细胞纤维新月体)的相关性.结果 (1)192例IgA肾病患者临床表现以蛋白尿合并血尿最多见,为72例(37.5%),依次为肾病综合征42例(21.9%),肾功能不全29例(15.1%),合并高血压72例(37.5%);(2)牛津病理分型中M1占60.0%,E1占55.2%,S1占46.9%,T0、T1、T2分别占59.9%、22.9%、17.2%,46.9%的患者存在小动脉内膜增厚,48.5%存在细胞或细胞纤维新月体,部分病理类型与年龄有关(P<0.01);(3)尿蛋白定量与系膜细胞增生、肾小管萎缩或间质纤维化、细胞或细胞纤维新月体有关(P <0.01或P<0.05).血压、肾功与节段硬化或粘连、肾小管萎缩或间质纤维化、小动脉内膜增厚、细胞或细胞纤维月体有关(P<0.01或P<0.05).结论 牛津病理分型对IgA肾病的治疗和预后评价有很好的指导作用.%Objective To investigate the relationship of the clinical characteristics and the Oxford classification of IgA nephropathy.Methods Clinical presentation (age,gender,course of disease,blood pressure,hematuria,24-hour proteinuria,serum creatinine,serum albumin,triglyceride,cholesterol,and estimated glomerular filtration rate (eGFR)),pathological data (mesangial hypercellularity,endocapillary hypercellularity,segmental sclerosis or adhesions,tubular atrophy or interstitial fibrosis,artery score,and cellular + fiberocellular crescents) and their correlation of 192 patients with IgA nephropathy patients were analyzed.Results (1)Clinically,hematuria + albuminuria type was the most common among 192 the patients

  11. Nefropatia por IgA em portadores de espondiloartrites acompanhados no Serviço de Reumatologia do Hospital das Clínicas da UFMG IgA nephropathy in patients with spondyloarthritis followed-up at the Rheumatology Service of Hospital das Clínicas/UFMG

    Directory of Open Access Journals (Sweden)

    Daniela Castelo Azevedo

    2011-10-01

    -B27 positivity, creatinine and urea serum levels, major comorbidities, hematuria and proteinuria. Patients with hematuria were subsequently assessed for the presence of dysmorphic red blood cells in urine, and those with proteinuria underwent 24-hour urine protein measurement. Renal biopsy was performed in patients with glomerular hematuria and/or proteinuria over 3.5 g/24-hour. RESULTS: Seventy-six patients were assessed. Microscopic hematuria was the most frequently found abnormality in urinalysis (44.7%, usually intermittent and in spot urine samples during patients' follow-up. In eight patients (10.5%, glomerular hematuria was suspected. Renal biopsy was performed in fi ve of them, showing IgA nephropathy in four (5.3% and thin membrane disease in one patient. CONCLUSIONS: A high frequency of urinalysis alterations was observed in that subgroup of patients, as well as a high prevalence of IgA nephropathy. Although further studies on this subject are needed to better clarify these results, periodic urinalysis of patients with spondyloarthritis should be recommended.

  12. 强直性脊柱炎合并IgA肾病与原发性IgA肾病临床资料对比研究%A comparative study of IgA nephropathy secondary to ankylosing spondylitis and primary IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    张洁; 黄烽; 张江林

    2015-01-01

    目的 通过对比强直性脊柱炎(AS)合并IgA肾病与原发性IgA肾病的临床资料,了解AS合并IgA肾病的特点.方法 检索2007年1月-2015年9月在我院行肾脏活检并确诊为IgA肾病的资料,其中AS合并IgA者纳入AS合并IgA肾病组,按1∶5比例随机抽取同期原发性IgA肾病者为原发性IgA肾病组;对比两组患者的临床资料、病理表现及预后转归.结果 AS合并IgA肾病组15例,原发性IgA肾病组75例;与原发性IgA肾病组比,AS合并IgA肾病组病程较短[(10.1±8.3)个月比(20.2±27.9)个月],出现肾功能不全和高血压的比例更低[1/15、1/15比52.0%(39/75)、46.7%(35/75)].AS合并IgA肾病组24 h尿蛋白定量、血肌酐水平低于原发性IgA肾病组[(1.42±0.67)g比(2.88±1.35)g;(79.0±18.2) mmol/L比(145.3 ±77.6) mmol/L].两组患者肾活检肾脏病理分型Lee分级为Ⅲ~Ⅴ级,差异无统计学意义.两组患者均接受糖皮质激素、免疫抑制剂、血管紧张素转化酶抑制剂或血管紧张素受体拮抗剂治疗.治疗1~6年后随访,AS合并IgA肾病组有3例(3/11)患者病情进一步恶化发展,而原发性IgA肾病组有13例(22.8%,13/57).结论AS合并IgA肾病患者较原发性IgA肾病患者病程更短,病情更轻,但针对原发病的治疗(包括糖皮质激素、免疫抑制剂、生物制剂)无法改变患者预后.%Objective To study the characteristics of IgA nephropathy (IgAN) secondary to ankylosing spondylitis (AS) compared with primary IgAN.Methods Clinical and pathologic data were collected in patients who were diagnosed with IgAN by renal biopsy and admitted to our hospital from Jan 2007 to Sep 2015.Patients with IgAN secondary to AS were recruited by the ratio 1 ∶ 5 of patients with primary IgAN as control group at the same period.Results There were 15 patients in AS group,proportionately 75 patients in the control group.Compared with those in control group,patients in AS group had shorter disease course [(10.1 ± 8

  13. Vogt-Koyanagi-Harada Syndrome in Two Patients with Immunoglobulin A Nephropathy

    Directory of Open Access Journals (Sweden)

    Sunami,Reiko

    2007-10-01

    Full Text Available We describe herein 2 patients who developed Vogt-Koyanagi-Harada syndrome in the course of renal biopsy-proven immunoglobulin A (IgA nephropathy. A 61-year-old man with an 11-year history of IgA nephropathy and a 16-year history of thyroiditis, and a 56-year-old man with a 5-year history of IgA nephropathy developed Vogt-Koyanagi-Harada syndrome. At the time of the eye disease presentation, IgA nephropathy was stable without corticosteroids in both patients. Vogt-Koyanagi-Harada syndrome was successfully treated with intravenous administration of prednisolone tapered from 200 mg daily. Vogt-Koyanagi-Harada syndrome is associated with IgA nephropathy, suggesting a similar autoimmune mechanism for both diseases.

  14. Hepatic-associated immunoglobulin-A nephropathy in a child with liver cirrhosis and portal hypertension

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    Sharifa A Alghamdi

    2012-01-01

    Full Text Available Hepatic-associated immunoglobulin A (IgA nephropathy is a relatively common condition that occurs in adults with liver cirrhosis and portal hypertension. However, it is rare in children. This condition is characterized by the deposition of IgA in the renal glomeruli. The present report describes a 14-year-old boy with cryptogenic liver cirrhosis and portal hypertension who presented with hematuria and proteinuria associated with histological changes of IgA nephropathy.

  15. The kinetics of glomerular deposition of nephritogenic IgA.

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    Kenji Yamaji

    Full Text Available Whether IgA nephropathy is attributable to mesangial IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce hematuria and subsequent proteinuria. This hinders the development of a specific therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of IgA nephropathy by nephritogenic IgA, we analyzed sequential events involving nephritogenic IgA from IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as hematuria.

  16. Radiogenic nephropathy; Radiogene Nephropathie

    Energy Technology Data Exchange (ETDEWEB)

    Gotthardt, M. [Univ. Medisch Centrum St Radboud, Nijmegen (Netherlands). Nucleaire Geneeskunde

    2010-07-01

    Patient-individual dosimetric analyses are a useful tool in external beam radiotherapy (EBR) to protect patients from side effects such as radiogenic nephropathy. At this point in time, individual dosimetry is not used as a standard in patient treated with radiolabelled antibody fragments or polypeptides. The reasons are a number of problems, which make patient dosimetry more challenging than in EBR. While in EBR, the dose is distributed evenly in the organ and the organ volume can exactly be determined, in internal radiotherapy the tracer is not evenly distributed within the organ leading to a non-uniform dose distribution. In addition, the dose rate of the most commonly used radionuclides is lower than in EBR and the range of their radiation differ, so that the radiobiological effects are differing considerably in comparison to EBR. Conclusion: More complex models have to be used for clinical kidney dosimetry in internal radiotherapy. In this paper, we give a concise overview of the reasons for accumulation of radiotracers in the kidney, the most recent developments in kidney dosimetry, and approaches to reduce the kidney uptake of radiotracers in order to avoid radiogenic nephropathy. (orig.)

  17. 伴有牙周炎的IgA肾病患者牙周治疗前后血清TNF-α与IL-8变化分析%Changes in levels of serum TNF-α and IL-8 before and after periodontal therapy for patients of IgA nephropathy with periodontitis

    Institute of Scientific and Technical Information of China (English)

    许志鹏; 宋勇; 孙燕

    2015-01-01

    Objective To examine the levels of serum tumor necrosis factor-α(TNF-α) and interleukin-8 (IL-8) for IgA nephropathy patients with periodontitis before and after periodontal therapy. Methods Fifty pa-tients of IgA nephropathy with chronic periodontitis (study group) and 30 healthy individuals (control group) were in-cluded in this study. The study group was treated by ultrasonic and VECTOR periodontal therapy apparatus, whereas the control group received no special treatment. We measured the periodontal indexes, and serum TNF-αand IL-8 lev-els by enzyme-linked immunosorbent assay (ELISA) at the visit of doctor in the control group as well as before treat-ment and 4 weeks after treatment in the study group. Results After periodontal therapy, the periodontal status was significantly improved, with the levels of periodontal indexes and serum TNF-α and IL-8 significantly decreased. Compared with the control group, the periodontal indexes and the serum TNF-αand IL-8 were still significantly higher. Conclusion Periodontal treatment can not only effectively improve the periodontal lesions and promote the recovery of periodontitis, but also reduce the levels of serum TNF-αand IL-8 and benefit the treatment for IgA nephropathy.%目的:观察伴有慢性牙周炎的IgA肾病患者牙周治疗前后血清肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)变化。方法选取伴有慢性牙周炎的IgA肾病患者50例(治疗组)和健康者30例(对照组)。对照组不予特殊处理,治疗组采用超声洁牙和VECTOR牙周治疗仪进行牙周治疗,对照组于初诊时,治疗组于治疗前及治疗后4周,分别检测两组受试者的牙周指数和血清TNF-α与IL-8的浓度。血清中TNF-α与IL-8的浓度采用酶联免疫吸附法测定。结果治疗组患者经过牙周治疗后,牙周状况明显好转,血清TNF-α与IL-8浓度与治疗前比较均明显降低,差异均有统计学意义(P<0.05),但是牙周指数、TNF-α和IL-8

  18. Acute Cresentric IgA Nephritis in a Patient with Hodgkin's Lymphoma

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    Ebru GÖK OĞUZ

    2014-09-01

    Full Text Available In glomerular diseases, the occurence of lymphoma is mostly observed in the form of both minimal change disease and Hodgkin’s lymphoma. The coocurrence of Membranous nephropathy and membranoproliferative glomerulonephritis are generally associated with non-Hodgkin’s lymphoma. While Ig A nephropathy-lymphoma association is rare, it is generally observed in the form of non- Hodgkin’s lymphoma, and there are also cases proposed the cooccurence of Ig A nephropathy and cutaneous T-cell lymphoma. In this case, it is emphasized that IgA nephropathy presented with cresentric glomerulonephritis should be considered in patients with hodgkin’s lymphoma who have sudden renal disorder.

  19. Suppression of Adiponectin by Aberrantly Glycosylated IgA1 in Glomerular Mesangial Cells In Vitro and In Vivo

    OpenAIRE

    Inoue, Tatsuyuki; Sugiyama, Hitoshi; Kitagawa, Masashi; Takiue, Keiichi; Morinaga, Hiroshi; Ogawa, Ayu; Kikumoto, Yoko; Kitamura, Shinji; Maeshima, Yohei; Makino,Hirofumi

    2012-01-01

    The pathogenesis of IgA nephropathy (IgAN) may be associated with the mesangial deposition of aberrantly glycosylated IgA1. To identify mediators affected by aberrantly glycosylated IgA1 in cultured human mesangial cells (HMCs), we generated enzymatically modified desialylated and degalactosylated (deSial/deGal) IgA1. The state of deglycosylated IgA1 was confirmed by lectin binding to Helix aspersa (HAA) and Sambucus nigra (SNA). In the cytokine array analysis, 52 proteins were upregulated an...

  20. Clinico-pathological characteristics and prognosis of IgA nephropathy patients with microalbuminuria and deposition of complement C3%微量白蛋白尿IgA肾病伴补体C3沉积患者的临床病理特征及预后分析

    Institute of Scientific and Technical Information of China (English)

    郭宗运; 周生国; 王营营; 李霞; 徐妍; 杜晓娅; 张伟; 吴玉梅

    2016-01-01

    Objective To analyze the clinical and pathological data and prognosis of IgA nephropathy patients with microalbuminuria and deposition of C3,and to investigate the significance of C3 deposition in IgA nephropathy with microalbuminuria.Methods The clinical and pathological data of 127 IgA nephropathy patients with microalbuminuria confirmed by renal biopsy in the Jining No.1 People's Hospital from January 2009 to January 2015 and minimum 6-month follow-up was reviewed,and patients were divided into positive group (72 cases,56.7%)and negative group (55 cases,43.3%) according to the deposition of C3 in the mesangial area of glomeruli.24 h urine quantitative protein being more than 1 g,or serum creatinine level becoming abnormal or double by renal biopsy was defined as endpoint of follow-up.Renal survival was calculated by Kaplan-Meier survival analysis.Results A total of 127 IgA nephropathy patients with microalbuminuria were followed up successfully,with an average follow-up of (49.6 ± 22.7) months.24 h urine albumin[(261.3 ±47.4) vs (238.7 ±51.9) mg,P =0.011],serum creatinine value [98.0(56.4,118.6) vs 85.7(51.9,107.8) μmol/L,P=0.003],uric acid value[(384.0 ±93.7) vs (360.5 ±88.4) μmol/L,P=0.043] and serum IgA value[(3.36 ± 1.17) vs (3.12 ± 1.05) g/L,P =0.044] were significantly higher in the C3 positive group than those in the negative group,while the serum complement C3 was significantly lower [(0.70 ± 0.42) vs (0.98 ± 0.49) mg,P =0.047].Pathological changes [Lee's grade Ⅲ and above Ⅲ:21 (16.5%) vs 11 (8.7%),P =0.034],glomerular sclerosis or adhesions [29 (22.8%) vs 19 (15.0%),P =0.047],renal tubular atrophy or interstitial fibrosis [13 (10.2%) vs 8 (6.3%),P =0.027] and crescent formation [7(5.5%) vs 2 (1.6%),P =0.035] in the complement C3 positive group were more severe than those in the negative group.38 cases of complement C3 positive group and 14 cases of negative group accomplished the study,and Kaplan-Meier survival

  1. Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?

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    Brandon S. Oberweis

    2013-01-01

    Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  2. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins

    OpenAIRE

    Moore, Jennifer S.; Kulhavy, Rose; Tomana, Milan; Moldoveanu, Zina; Brown, Rhubell; Hall, Stacy; Kilian, Mogens; Poulsen, Knud; Mestecky, Jiri; Julian, Bruce A.; Novak, Jan

    2007-01-01

    Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize potential differences in recognition of terminal N-acetylgalactosamine (GalNAc) on IgA1, we evaluated ...

  3. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins

    DEFF Research Database (Denmark)

    Moore, J.S.; Kulhavy, R.; Tomana, M.;

    2007-01-01

    Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins...... exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize potential differences in recognition of terminal N-acetylgalactosamine (GalNAc) on IgA1, we evaluated the binding characteristics of several commercial preparations of GalNAc-specific lectins using a panel...... of IgA1 and, as controls, IgA2 and IgG myeloma proteins. These lectins originated from snails Helix aspersa (HAA) and Helix pomatia (HPA), and the plant Vicia villosa (VV). Only HAA and HPA bound exclusively to IgA1, with its O-linked glycans composed of GalNAc, galactose, and sialic acid. In...

  4. Binding capacity of in vitro deglycosylated IgA1 to human mesangial cells.

    Science.gov (United States)

    Zhang, Jun-jun; Xu, Li-xia; Zhang, Ying; Zhao, Ming-hui

    2006-04-01

    IgA nephropathy (IgAN) is the most common glomerular disease and it is characterized by deposition of IgA1 molecules in mesangium. Recent studies had demonstrated that serum and mesangial IgA1 in IgAN were deglycosylated and IgA1 could bind to human mesangial cells (HMC) through a novel receptor. The aim of the current study is to investigate and compare the binding capacities of different in vitro deglycosylated IgA1 on human mesangial cells. Serum IgA1 was purified by jacalin affinity chromatography and then was desialylated (DesIgA1) and/or degalactosylated (Des/DeGalIgA1) with neuraminidase and/or beta-galactosidase. The efficacy of deglycosylations was assessed by Peanut agglutinin (PNA) and Vicia villosa (VV) lectin. The sizes of normal IgA1 and deglycosylated IgA1 were determined by Sephacryl S-300 chromatography and binding capacities to primary HMC were evaluated by radioligand binding assays. Normal IgA1 and deglycosylated IgA1 could bind to HMC in a dose-dependent, saturable manner. The maximal binding capacities and binding sites/cell of DesIgA1 and Des/DeGalIgA were significantly higher than that of normal IgA1. However, more aggregated IgA1 was found in DesIgA1 and Des/DeGalIgA1. Scatchard analysis revealed a similar Kd of normal IgA1 and deglycosylated IgA1. The current study suggested that the binding capacities of DesIgA1 and Des/DeGalIgA1 to HMC were significantly higher than that of normal IgA1, which at least in part was due to more macromolecular IgA1 in deglycoslated IgA1. However, there were no significant differences in the affinities of normal IgA1, DesIgA1 and Des/DeGalIgA1 with HMC. Deglycosylated IgA1 might play an important role in pathogenesis of IgAN. PMID:16442846

  5. Radiogenic nephropathy

    International Nuclear Information System (INIS)

    Patient-individual dosimetric analyses are a useful tool in external beam radiotherapy (EBR) to protect patients from side effects such as radiogenic nephropathy. At this point in time, individual dosimetry is not used as a standard in patient treated with radiolabelled antibody fragments or polypeptides. The reasons are a number of problems, which make patient dosimetry more challenging than in EBR. While in EBR, the dose is distributed evenly in the organ and the organ volume can exactly be determined, in internal radiotherapy the tracer is not evenly distributed within the organ leading to a non-uniform dose distribution. In addition, the dose rate of the most commonly used radionuclides is lower than in EBR and the range of their radiation differ, so that the radiobiological effects are differing considerably in comparison to EBR. Conclusion: More complex models have to be used for clinical kidney dosimetry in internal radiotherapy. In this paper, we give a concise overview of the reasons for accumulation of radiotracers in the kidney, the most recent developments in kidney dosimetry, and approaches to reduce the kidney uptake of radiotracers in order to avoid radiogenic nephropathy. (orig.)

  6. Immunoglobulin A Nephropathy and Malaria falciparum Infection; a Rare Association

    Directory of Open Access Journals (Sweden)

    Mahmoud Rafieian-Kopaei

    2013-05-01

    Full Text Available Glomerular involvement occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Here, we report a rare case of falciparum malaria-associated IgA nephropathy. A 28-year-old man was admitted because of fever and abdominal pain. Ultrasound and computed tomography (CT showed right kidney pyonenphrosis. Despite placing a nephrostomy tube, fever continued. Repeated CT was in favor of focal pyelonephritis. In addition, peripheral blood smear suggested malaria. Anti-malarial drugs were initiated and right nephrectomy was performed. One year after recovery from malaria, a persistent rise in serum creatinine was detected. A left kidney biopsy showed mesangial proliferation and dominant IgA deposits in immunofluorescence study while C1q was not deposited. The impression was IgA nephropathy with M1E0S0T0 of Oxford classification. The patient was prescribed a combination of low dose prednisolone and angiotensin converting enzyme inhibitor. Six months after treatment serum creatinine decreased from 1.6 mg/dL to 1.3mg/dL and urine abnormalities were disappeared. Our findings suggest that malaria infection might be associated with IgA nephropathy.

  7. 肾小管肝型脂肪酸结合蛋白对小鼠IgA肾病的肾脏保护作用%Protective effects of tubular liver-type fatty acid binding protein on murine IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    佐楠; 李艳秋; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    目的 探讨近曲小管肝型脂肪酸结合蛋白(L-FABP)对骨髓移植诱导的小鼠IgAN的肾脏保护作用.方法 通过骨髓移植在肾小管高表达人类L-FABP(hL-FABP)基因的转基因鼠(Tg)和相同背景的野生鼠(WT)上重建IgAN.受体鼠分别在骨髓移植后第6和12周处死,留取肾脏标本.用实时荧光定量PCR方法检测肾脏hL-FABP、纤连蛋白(FN)和单核细胞趋化蛋白1(MCP-1)的mRNA表达;免疫组化法检测hL-FABP和FN的蛋白表达分布;Western印迹法检测hL-FABP、4-羟壬烯醛(4-HNE)、血红素加氧酶1(HO-1)、FN、Ⅳ型胶原的蛋白表达水平;ELISA法检测血清IgA、尿白蛋白和尿hL-FABP水平.结果 骨髓移植在受体转基因鼠(Tg-ddY)和野生鼠(WT-ddY)上均重建了IgAN,血清IgA水平升高伴有系膜区IgA沉积,组间差异无统计学意义.正常Tg鼠的肾小管表达hL-FABP.与正常Tg鼠相比,骨髓移植后第6周,Tg-ddY鼠肾脏hL-FABP的mRNA(1.62±0.32比0.46±0.09,P<0.01)和蛋白(1.74±0.76比1.14±0.31,P<0.01)表达水平显著上调,伴有尿hL-FABP水平(μg/g肌酐)显著升高(59.87±26.75比31.01±14.86,P<0.05).与Tg-ddY鼠相比,WT-ddY鼠在第12周出现明显的白蛋白尿(mg/L)(828±656比82±22,P<0.01)、明显的系膜基质扩张(P<0.01),并在肾小球出现更多的FN及Ⅳ型胶原沉积.Tg-ddY鼠的肾脏HO-1和4-HNE修饰蛋白(均P<0.05)以及MCP-1 mRNA的表达(P<0.01)被显著抑制.结论 肾小管L-FABP可能通过抑制氧化应激和炎性介质的产生减轻肾小球损伤,在IgAN早期发挥了肾脏保护作用.%Objective To investigate the renoprotection of tubular L-FABP in murine IgA nephropathy (IgAN) induced by bone marrow transplantation(BMT). Methods IgAN models were reconstituted by BMT from IgAN-prone mice into mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP) and wild type (WT) mice. These recipients were sacrificed at 6 and 12 weeks after BMT and their kidneys were collected. The expressions

  8. Silica nephropathy.

    Science.gov (United States)

    Ghahramani, N

    2010-07-01

    Occupational exposure to heavy metals, organic solvents and silica is associated with a variety of renal manifestations. Improved understanding of occupational renal disease provides insight into environmental renal disease, improving knowledge of disease pathogenesis. Silica (SiO2) is an abundant mineral found in sand, rock, and soil. Workers exposed to silica include sandblasters, miners, quarry workers, masons, ceramic workers and glass manufacturers. New cases of silicosis per year have been estimated in the US to be 3600-7300. Exposure to silica has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease and end-stage renal disease. A rare syndrome of painful, nodular skin lesions has been described in dialysis patients with excessive levels of silicon. Balkan endemic nephropathy is postulated to be due to chronic intoxication with drinking water polluted by silicates released during soil erosion. The mechanism of silica nephrotoxicity is thought to be through direct nephrotoxicity, as well as silica-induced autoimmune diseases such as scleroderma and systemic lupus erythematosus. The renal histopathology varies from focal to crescentic and necrotizing glomerulonephritis with aneurysm formation suggestive of polyarteritis nodosa. The treatment for silica nephrotoxicity is non-specific and depends on the mechanism and stage of the disease. It is quite clear that further research is needed, particularly to elucidate the pathogenesis of silica nephropathy. Considering the importance of diagnosing exposure-related renal disease at early stages, it is imperative to obtain a thorough occupational history in all patients with renal disease, with particular emphasis on exposure to silica, heavy metals, and solvents. PMID:23022796

  9. Silica Nephropathy

    Directory of Open Access Journals (Sweden)

    N Ghahramani

    2010-06-01

    Full Text Available Occupational exposure to heavy metals, organic solvents and silica is associated with a variety of renal manifestations. Improved understanding of occupational renal disease provides insight into environmental renal disease, improving knowledge of disease pathogenesis. Silica (SiO2 is an abundant mineral found in sand, rock, and soil. Workers exposed to silica include sandblasters, miners, quarry workers, masons, ceramic workers and glass manufacturers. New cases of silicosis per year have been estimated in the US to be 3600–7300. Exposure to silica has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease and end-stage renal disease. A rare syndrome of painful, nodular skin lesions has been described in dialysis patients with excessive levels of silicon. Balkan endemic nephropathy is postulated to be due to chronic intoxication with drinking water polluted by silicates released during soil erosion. The mechanism of silica nephrotoxicity is thought to be through direct nephrotoxicity, as well as silica-induced autoimmune diseases such as scleroderma and systemic lupus erythematosus. The renal histopathology varies from focal to crescentic and necrotizing glomerulonephritis with aneurysm formation suggestive of polyarteritis nodosa. The treatment for silica nephrotoxicity is non-specific and depends on the mechanism and stage of the disease. It is quite clear that further research is needed, particularly to elucidate the pathogenesis of silica nephropathy. Considering the importance of diagnosing exposure-related renal disease at early stages, it is imperative to obtain a thorough occupational history in all patients with renal disease, with particular emphasis on exposure to silica, heavy metals, and solvents.

  10. Relationship of polymorphism of megsin C2093T and C2180T with IgA nephrology:a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Dan WU

    2011-02-01

    Full Text Available Objective To analyze the relation between the polymorphism of megsin C2093T and C2180T gene and IgA nephropathy.Methods Studies related to the relation of polymorphism of megsin C2093T and C2180T to IgA nephropathy were authenticated from databases including Medline,Embase and Cochrane Library from Jan.1980 to Aug.2010.The cited literature of obtained articles and some core English and Chinese medical journals relevant to nephropathy were also searched by hand(2000 to Aug.2010.The data were analyzed by RevMan 5.0 software.Results Five papers were finally included,meta-analysis results showed that there was statistical difference between megsin 2093C allele and risk for IgA nephropathy [odds ratio(OR = 1.20,95% CI 1.04 to 1.40].No statistical difference existed between megsin 2093CC genotype and risk for IgA nephropathy(OR=1.18,95% CI 0.90 to 1.55.In Asian subgroups,there was significant difference between megsin 2093C allele and risk for IgA nephropathy(OR=1.19,95% CI 1.01 to 1.40,while no significant association existed between megsin 2093CC genotype and risk for IgA nephropathy(OR=1.19,95% CI 0.88 to 1.61.Also,no significant difference was revealed in the total meta-analysis between the megsin 2180C allele and risk for IgA nephropathy(OR=0.89,95%CI 0.72 to 1.10 or CC genotype and risk for IgA nephropathy(OR=1.04,95%CI 0.69 to 1.56.Moreover,no significant difference was found between megsin 2093 and 2180C allele and IgA nephropathy progression(OR=0.89,95%CI 0.69 to 1.15;OR=0.84,95%CI 0.48 to 1.46,respectively.There was also no significant difference between megsin 2093 and 2180CC genotype and IgA nephropathy progression(OR=0.80,95%CI 0.42 to 1.49;OR=0.79,95%CI 0.32 to 1.93,respectively.Significant difference was found between the 2093T-2180T haplotype and IgA nephropathy progression(OR=0.54,95%CI 0.33 to 0.87.Conclusion Megsin 2093C allele is the susceptible gene of IgA nephropathy,while megsin 2093 genotype,2180 allele or genotype are not

  11. IgA Nephropathy: Molecular Mechanisms of the Disease

    Czech Academy of Sciences Publication Activity Database

    Městecký, Jiří; Raška, M.; Julian, B. A.; Gharavi, A. G.; Renfrow, M. B.; Moldoveanu, Z.; Novák, L.; Matoušovič, K.

    2013-01-01

    Roč. 8, č. 2013 (2013), s. 217-240. ISSN 1553-4006 Institutional support: RVO:61388971 Keywords : O-glycosylation * hinge region * circulating immune complexes Subject RIV: EC - Immunology Impact factor: 22.128, year: 2013

  12. Mesangial C3 deposition and decreased serum C3 levels in patients with IgA nephropathy%补体C3系膜区沉积与低C3血症在IgA肾病中的意义

    Institute of Scientific and Technical Information of China (English)

    章晓炎; 谢静远; 王伟铭; 王朝晖; 潘晓霞; 沈平雁; 徐静; 郝旭; 周琼秀

    2014-01-01

    目的 对IgA肾病(IgAN)患者的临床及病理资料进行分析,旨在探讨补体活化在IgAN中的意义,为临床治疗提供依据.方法 回顾性分析本院确诊的原发性IgAN患者,记录患者基线一般情况、临床指标、病理学检查及随访结果.根据免疫荧光下补体C3在系膜区沉积情况,分为阴性、弱阳性、强阳性3组,血C3降低组的定义为血清C3< 85 mg/dl.结果 本研究纳入528例患者,平均随访3年.肾组织C3沉积阴性组、弱阳性组、强阳性组患者分别为119例(22.5%)、164例(31.1%)和245例(46.4%);血C3降低组患者93例(21.7%),血C3正常组335例(78.3%);系膜区C3沉积与血清C3水平呈负相关(r=-0.209,P<0.01);不同肾组织C3沉积组间年龄、性别差异无统计学意义;随肾组织C3沉积加重,患者基线血肌酐、尿酸、血IgA水平升高,估算肾小球滤过率(eGFR)、体质量指数(BMI)降低(P<0.05),C3沉积较多的患者肾组织毛细血管内细胞增生和肾小管萎缩、肾间质纤维化更为严重(P< 0.05).与血C3正常组比较,血C3降低组患者白细胞、血红蛋白、三酰甘油、胆固醇、eGFR水平较低,而血肌酐水平较高(P<0.05).随访期间,共有54例患者进入终末期肾病(ESRD),血C3降低组ESRD发生率为23.7%,正常组为8.4%,Kaplan-Meier分析显示血C3降低组肾脏中位生存时间显著低于C3正常组[(145.0±22.5)个月比(150.8±17.0)个月,P<0.01].Cox回归分析显示,校正性别、年龄和临床指标(平均动脉压、eGFR、白蛋白、尿蛋白、血红蛋白水平)后,血清C3降低(HR=0.97,95%CI 0.96,0.99,P<0.01)为患者进入ESRD的独立危险因素.结论 IgAN患者存在不同程度补体系统活化,补体活化与患者基础肾功能及临床预后相关,血清C3下降为患者进入ESRD的独立危险因素,提示补体活化可能参与IgAN的进程.%Objective To explore the clinical significance of complement activation in IgA nephropathy (Ig

  13. Proliferative retinopathy predicts nephropathy

    DEFF Research Database (Denmark)

    Karlberg, Charlotte; Falk, Christine; Green, Anders;

    2012-01-01

    We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the sa...

  14. Immunoglobulin A nephropathy: Basic characteristics

    Directory of Open Access Journals (Sweden)

    Petrović Lada

    2003-01-01

    Full Text Available Introduction Immunoglobulin A nephropathy (IgAN is one of the most common forms of primary glomerulonephritis in many countries. Most clinical features of IgAN point to a renal problem, such as recurrent macroscopic hematuria or asymptomatic microscopic hematuria and proteinuria. Pathologic features of IgAN present with different types and different degrees of glomerular tubulointerstitial and vascular lesions. The aim of this study was detailed analysis of clinical and laboratory findings, as well as findings of immunofluorescence and light microscopy. We also investigated associations between these factors. Material and methods We investigated 60 patients who underwent renal biopsy. The study was partly retrospective and partly prospective. Results The average age of patients was 34.19 years. Male female ratio was 2.33:1. IgAN was most frequently asymptomatic (83.33% as microhematuria and proteinuria, while gross hematuria was found in 16.667%. Renal biopsy material was analyzed by light microscopy revealing changes in all glomerular structures. Immunofluorescence microscopy demonstrated dominant IgA deposits. This study established association of glomerulosclerosis with clinical features of disease. Discussion and conclusions IgAN frequently develops in the 4th decade of life, mostly in males and presents as asymptomatic (83.33%. Patohistological changes include all glomerular structures. There is no specific serological test for IgAN, but pathological changes affect clinical features of the disease, as proteinuria and increase of creatinine concentration.

  15. Reactivities of N-acetylgalactosamine-specific lectins with human IgA1 proteins.

    Science.gov (United States)

    Moore, Jennifer S; Kulhavy, Rose; Tomana, Milan; Moldoveanu, Zina; Suzuki, Hitoshi; Brown, Rhubell; Hall, Stacy; Kilian, Mogens; Poulsen, Knud; Mestecky, Jiri; Julian, Bruce A; Novak, Jan

    2007-04-01

    Lectins are proteins with specificity of binding to certain monosaccharides or oligosaccharides. They can detect abnormal glycosylation patterns on immunoglobulins in patients with various chronic inflammatory diseases, including rheumatoid arthritis and IgA nephropathy (IgAN). However, lectins exhibit binding heterogeneity, depending on their source and methods of isolation. To characterize potential differences in recognition of terminal N-acetylgalactosamine (GalNAc) on IgA1, we evaluated the binding characteristics of several commercial preparations of GalNAc-specific lectins using a panel of IgA1 and, as controls, IgA2 and IgG myeloma proteins. These lectins originated from snails Helix aspersa (HAA) and Helix pomatia (HPA), and the plant Vicia villosa (VV). Only HAA and HPA bound exclusively to IgA1, with its O-linked glycans composed of GalNAc, galactose, and sialic acid. In contrast, VV reacted with sugars of both IgA subclasses and IgG, indicating that it also recognized N-linked glycans without GalNAc. Furthermore, HAA and HPA from several manufacturers differed in their ability to bind various IgA1 myeloma proteins and other GalNAc-containing glycoproteins in ELISA and Western blot. For serum samples from IgAN patients, HAA was the optimal lectin to study IgA1 glycosylation in ELISA and Western blot assays, including identification of the sites of attachment of the aberrant glycans. The galactose-deficient glycans were site-specific, localized mostly at Thr228 and/or Ser230. Because of the heterogeneity of GalNAc-specific lectins, they should be carefully characterized with appropriate substrates before undertaking any study. PMID:17275907

  16. OBSTRUCTIVE NEPHROPATHY: ITS PHYSIOPATHOLOGY

    Directory of Open Access Journals (Sweden)

    Musso C

    2011-01-01

    Full Text Available Obstructive nephropathy is the functional and /or parenchymal renal damage secondary to the urinary tract occlusion at any part of it. The inducing urinary obstruction diseases can vary depending on the patient´s age and gender. There are many renal dysfunction inducing mechanisms involved in this entity: increase in the intra-luminal pressure, ureteral dilatation with ineffective ureteral peristalsis, glomerular ultrafiltration net pressure reduction, intra-renal glomerular blood flux reduction due to vasoconstriction, and local disease of chemotactic substances. Obstructive nephropathy can also lead to hypertension (vasoconstriction-hypervolemia, hyperkalemia, metabolic acidosis (aldosterone resistance, diabetes insipidus (vasopressine resistance. In conclusion, since obstructive nephropathy is a potentially reversible cause of renal dysfunction, it should always be taken into account among the differential diagnosis of renal failure inducing mechanisms.

  17. Kaliopenic nephropathy revisited.

    Science.gov (United States)

    Elitok, Saban; Bieringer, Markus; Schneider, Wolfgang; Luft, Friedrich C

    2016-08-01

    In the 'older' literature, a definitive renal pathology was described in patients with long-standing hypokalaemia and depletion of the body's potassium reserves. The topic is relevant because possibly a quite cheaply reversible element in the course of chronic kidney disease progression could be addressed. Earlier, pathologists drew attention to vacuolar changes in renal tubular epithelium accompanied by inflammatory interstitial changes in patients with potassium losses. The diagnostic term 'kaliopenic nephropathy' was coined to describe such patients. Kaliopenic nephropathy now receives less emphasis than in earlier times. However, with eating disorders, laxative abuse and other potential causes, we suggest that the syndrome should be resurrected. PMID:27478593

  18. Iga viies SVH on ennetatav

    Index Scriptorium Estoniae

    2009-01-01

    ONTARGET uuring tõestab, et telmisartaan kaitseb kõrge kardiovaskulaarse riskiga patsiente sama tõhusalt kui ramipriil, kuid on paremini talutav. Uuringust võib järeldada, et telmisartaaniga saab ennetada iga viiendat tõsist kardiovaskulaarset juhtumit. Eesti arstidele tutvustati uuringut 6. mail toimunud sümpoosiumil

  19. Phospholipase A2 receptor positive membranous nephropathy long after living donor kidney transplantation between identical twins.

    Science.gov (United States)

    Saito, Hisako; Hamasaki, Yoshifumi; Tojo, Akihiro; Shintani, Yukako; Shimizu, Akira; Nangaku, Masaomi

    2015-07-01

    Although membranous nephropathy (MN) is a commonly observed cause of post-transplant glomerulonephritis, distinguishing de novo from recurrent MN in kidney allograft is often difficult. Phospholipase A2 receptor (PLA2R) staining is useful for diagnosing recurrent MN in allografts similarly to idiopathic MN in native kidney. No specific treatment strategy has been established for MN, especially when accompanied with HCV infection in kidney transplant recipients. This report describes a 66-year-old man who was diagnosed as having PLA2R positive membranous nephropathy accompanied with already-known IgA nephropathy and HCV infection 26 years after kidney transplantation conducted between identical twins. PLA2R was detected along capillary loops, implying that this patient is affected by the same pathogenic mechanism as idiopathic MN, not secondary MN associated with other disorders such as HCV infection. The patient successfully achieved clinical remission after steroid therapy. PMID:26031599

  20. Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy%系膜细胞源性肿瘤坏死因子α上调IgA肾病肾小管肝型脂肪酸结合蛋白的表达及其肾脏保护作用

    Institute of Scientific and Technical Information of China (English)

    佐楠; 栗霄立; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P<0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P<0.05 and P<0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P<0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P <0.05 and P<0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.%目的 探讨体外近曲小管肝型脂肪酸结合蛋白(L-FABP)在IgA肾病(IgAN)中的上调机制及其对肾脏的保护作用.方法 原代培养的小鼠系膜

  1. Mouse Models of Diabetic Nephropathy

    OpenAIRE

    Brosius, Frank C.; Alpers, Charles E.; Bottinger, Erwin P.; Breyer, Matthew D.; Coffman, Thomas M.; Gurley, Susan B.; Harris, Raymond C.; Kakoki, Masao; Kretzler, Matthias; Leiter, Edward H.; Levi, Moshe; McIndoe, Richard A.; Sharma, Kumar; Smithies, Oliver; Susztak, Katalin

    2009-01-01

    Diabetic nephropathy is the major cause of end-stage renal disease worldwide. Despite its prevalence, identification of specific factors that cause or predict diabetic nephropathy has been delayed in part by lack of reliable animal models that mimic the disease in humans. The Animal Models of Diabetic Complications Consortium (AMDCC) was created 8 years ago by the National Institutes of Health to develop and characterize models of diabetic nephropathy and other complications. This interim rep...

  2. Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Qiang Zhou

    2011-01-01

    Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

  3. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter;

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic...... measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  4. Contrast induced nephropathy

    DEFF Research Database (Denmark)

    Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter;

    2011-01-01

    PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic...... measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml....../min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR = 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally....

  5. Scorpion sting nephropathy

    OpenAIRE

    Viswanathan, Stalin; Prabhu, Chaitanya

    2011-01-01

    Scorpion envenomations are ubiquitous, but nephropathy is a rare manifestation, reported mainly from the Middle East and North Africa. Rapid venom redistribution from blood, delayed excretion from the kidneys, direct toxicity of venom enzymes, cytokine release and afferent arteriolar constriction have been seen in experimental animals. Haemoglobinuria, acute tubular necrosis, interstitial nephritis and haemolytic–uraemic syndrome have been documented in human victims of scorpion envenomation....

  6. Nephropathy in leptospirosis

    OpenAIRE

    Visith S; Kearkiat P

    2005-01-01

    Renal involvement is common in leptospirosis. Bacterial invasion, inflammatory process, haemodynamic alterations and direct toxicity of bacterial products are thought to be responsible for the development of nephropathy. Pathologically, all renal structures are involved. Interstitial nephritis is the basic lesion, and is observed even in patients without clinical renal manifestations. Tubular necrosis is the important pathological counterpart of acute renal failure. The clinical spectrum of r...

  7. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Man [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Li, Fu-gang [Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China); Xie, Xi-sheng [Department of Nephrology, Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong City 637400 (China); Wang, Shao-qing [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Fan, Jun-ming, E-mail: junmingfan@163.com [Department of Nephrology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City 610500 (China); Department of Nephrology, Affiliated Hospital of Luzhou Medical College, Luzhou City 646000 (China)

    2014-02-07

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

  8. CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells

    International Nuclear Information System (INIS)

    Highlights: • CagA stimulated cell proliferation and the production of IgA1 in DAKIKI cells. • CagA promoted the underglycosylation of IgA1 in DAKIKI cells. • CagA decreased the expression of C1GALT1 and its chaperone Cosmc in DAKIKI cells. • Helicobacter pylori infection may participate in the pathogenesis of IgAN via CagA. - Abstract: While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of β1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells

  9. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  10. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases.

    Science.gov (United States)

    Senior, B W; Dunlop, J I; Batten, M R; Kilian, M; Woof, J M

    2000-02-01

    To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the hybrid molecule, as judged by its ability to bind to IgA Fcalpha receptors and trigger respiratory bursts in neutrophils. Although the IgA2/A1 hybrid contained only half of the IgA1 hinge, it was found to be cleaved by a variety of different bacterial IgA1 proteases, including representatives of those that cleave IgA1 in the different duplicated halves of the hinge, namely, those of Prevotella melaninogenica, Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition. PMID:10639405

  11. Radionuclide diagnosis of diabetic nephropathy

    International Nuclear Information System (INIS)

    The authors report the results of investigation of the state of filtration-excretory function of the kidneys, renal hemodynamics in patients with type I diabetes mellitus and stage II and III diabetic nephropathy

  12. ANTIOXIDANT STATUS IN DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Giriraja

    2015-12-01

    Full Text Available BACKGROUND Hyperglycemia and dislipidemia in DM induce increased lipid peroxdation and free radical formation. This is an important mechanism of microangiopathy. AIM To measure the antioxidant status in type 2 DM with nephropathy and compared with nondiabetic control group. MATERIALS AND METHODS 50 type 2 DM patients aged between 50 to 70 years according to national diabetes data group criteria with nephropathy diagnosed on the basis of history, physical examination and biochemical parameters were included. 50 age and sex matched apparently healthy individuals with normal plasma glucose, normal renal parameters and with no symptoms suggestive of DM were taken as controls. RESULTS Antioxidant status was significantly less in patients with diabetic nephropathy. CONCLUSION Data suggests that alteration in antioxidant status may help predict the risk of diabetic nephropathy.

  13. GENETICS ASPECTS OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Oana-Elena Sauca

    2010-09-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alteration, and various growth and genetic factors. The identification of the main genes would allow the detection of those individuals at high risk for diabetic nephropathy and better understanding of its pathophysiologyas well.The present review discusses the main information available in literature regarding some genetic variants (involved in the renin-angiotensin system, glucose and lipid metabolism and some cytoskeleton proteins that reaffirms the importance of genetic factors in diabetic nephropathy.

  14. Angiopoietins and diabetic nephropathy.

    Science.gov (United States)

    Gnudi, Luigi

    2016-08-01

    Diabetic nephropathy is the main cause of end-stage renal failure in the Western world. In diabetes, metabolic and haemodynamic perturbations disrupt the integrity of the glomerular filtration barrier, leading to ultrastructural alterations of the glomeruli, including podocyte foot process fusion and detachment, glomerular basement membrane thickening, reduced endothelial cell glycocalyx, and mesangial extracellular matrix accumulation and glomerulosclerosis, ultimately leading to albuminuria and end-stage renal disease. Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology. In normal physiology angiopoietins regulate the function of the glomerular filtration barrier. When they are dysregulated, however, as they are in diabetes, they drive the cellular mechanisms that mediate diabetic glomerular pathology. Modulation of angiopoietins expression and signalling has been proposed as a tool to correct the cellular mechanisms involved in the pathophysiology of diabetic microvascular disease, such as retinopathy in humans. Future work might evaluate whether this novel therapeutic approach should be extended to diabetic kidney disease. PMID:27207083

  15. Outcomes of renal transplantation in patients with immunoglobulin A nephropathy in India

    Directory of Open Access Journals (Sweden)

    Chacko B

    2007-01-01

    Full Text Available Background: There is a paucity of data on the course of renal transplant in patients with immunoglobulin A (IgA nephropathy (IgAN from India. While the natural history of IgAN in the Indian context is rapidly progressive, the post-transplant course remains speculative. Aim: To study the graft survival in renal transplant recipients whose native kidney disease was IgAN and the incidence and correlates of recurrent disease. Settings and Designs: Retrospective case control study from a Nephrology unit of a large tertiary care center. Materials and Methods: The outcomes of 56 transplant patients (58 grafts with biopsy-proven IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted during the same period were analyzed. Correlates of biopsy-confirmed recurrent disease were determined. Statistical Analysis: Means were analyzed by Student′s t test and Mann-Whitney test; proportions were determined by Chi-square analysis and graft survival curves were generated using the Kaplan-Meier. Results: Five-year graft survival for IgA patients was not significantly different from that in the reference group (90% and 79%, P = 0.6. During a mean follow-up of 42 months (range, 1-144, 28 event graft biopsies were required in 20 grafts of IgAN. Histological recurrence was diagnosed in five of the 20 available biopsies (25% after a mean duration of 28 months. Recurrence did not correlate with donor status, HLA B35 and A2, recipient age, gender or immunosuppression. Conclusions: Renal transplantation is an appropriate treatment modality for IgA nephropathy patients with end-stage renal disease in India, despite the potential for recurrent disease. The posttransplant course is an indolent one when compared to the malignant pretransplant phase.

  16. Videokonverentsiseadmete turg kahekordistub iga aasta / Jaak Ruusmaa

    Index Scriptorium Estoniae

    Ruusmaa, Jaak

    2005-01-01

    Ilmunud ka: Delovõje Vedomosti 24. aug. lk. 15. Videokonverentsiseadmete müük on Eestis viimase kuue aasta jooksul iga aasta keskmiselt kahekordistunud. Tabel: Videokonverentsiseade hoiab kulusid kokku

  17. Haridus - iga lapse õigus / Gerd Tarand

    Index Scriptorium Estoniae

    Tarand, Gerd, 1985-

    2009-01-01

    MTÜ Mondo alustas veebruaris maailmaharidusprojektiga „Haridus - iga lapse õigus“, mille üldine eesmärk on tõsta Eesti elanikkonna, eriti noorte huvi arengumaade vastu ning teadmisi ja arusaamist arengumaade haridusega seonduvatest probleemidest

  18. The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease

    Science.gov (United States)

    Hui, Gar Kay; Wright, David W.; Vennard, Owen L.; Rayner, Lucy E.; Pang, Melisa; Yeo, See Cheng; Gor, Jayesh; Molyneux, Karen; Barratt, Jonathan; Perkins, Stephen J.

    2015-01-01

    Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s020,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn263 were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN. PMID:26268558

  19. Characterization of nephritogenic IgA immune complexes separated by polyethylene glycol

    Energy Technology Data Exchange (ETDEWEB)

    Imai, H.; Rifai, A.

    1986-03-05

    The size of IgA immune complexes (IgA-IC) plays an important role in the pathogenesis of experimental IgA nephropathy. The ability of different concentrations (3.5%, 5% and 7% w/v) of polyethylene glycol (PEG) to selectively precipitate IgA-IC with defined size, was examined using convalently cross-linked /sup 125/I-radiolabelled IgA-IC. These complexes were prepared with purified IgA anti-dinitrophenyl (DNP) antibodies and bis-DNP-pimelic acid ester. Size analysis of IgA-IC by gradient polyacrylamide gel electrophoresis (GPAGE) revealed a composition of 33% large-size (> 2 x 10/sup 6/ mw), 39% intermediate-size (4-20 x 10/sup 5/ mw), and 28% mixture of dimer and monomer IgA. The standard 3.5% PEG precipitated less than 7% of large- and intermediate-size IgA-IC. In contrast, 5% and 7% PEG precipitated 40% and 100% of large-size complexes, respectively. The 7% PEG was also effective in precipitating (40%) of the intermediate-size complexes. The correlation between PEG concentration and size of the precipitated IgA-IC was further confirmed by GPAGE and quantitative autoradiography of resolubilized PEG precipitates of discrete size IgA-IC obtained by gel filtration. They conclude the standard 3.5% PEG is inappropriate for precipitation of IgA-IC and recommend the use of 7% PEG for the detection of intermediate- and large-size IgA-IC.

  20. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    Science.gov (United States)

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease. PMID:26971743

  1. Podocyte Pathology and Nephropathy

    Directory of Open Access Journals (Sweden)

    Sandra eMerscher

    2014-07-01

    Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

  2. Lithium nephropathy: a case report

    Directory of Open Access Journals (Sweden)

    Raphael Reis Pereira-Silva

    2014-01-01

    Full Text Available Although widely used in the management of bipolar disorder, lithium may cause adverse kidney effects. The importance of the present study is to report the case of a 59-year-old woman who was under regular treatment with lithium for bipolar disorder and whose imaging studies demonstrated the presence of multiple renal microcysts, suggesting lithium nephropathy as main diagnostic hypothesis.

  3. Membranous nephropathy in sibling cats.

    Science.gov (United States)

    Nash, A S; Wright, N G

    1983-08-20

    Membranous nephropathy was diagnosed in two sibling cats from the same household. Both cases presented with the nephrotic syndrome but 33 months elapsed before the second cat became ill, by which time the first cat had been in full clinical remission for over a year. PMID:6623883

  4. Evaluation of Children with IgA Nephropathy According to the Oxford Classification

    Directory of Open Access Journals (Sweden)

    Yel, Sibel

    2013-01-01

    Full Text Available OBJECTIVE: In this study, we aim to evaluate the clinical findings and short term results of our patients with IgAN according to Oxford classification.MATERIAL and METHODS: The medical records and the renal biopsy findings of 25 patients with IgAN were retrospectively reviewed. According to the pathological findings in Oxford classification, those without obvious disorder were accepted as Group 1 (n=16, and those with obvious disorders were accepted as Group 2 (n=9.These groups were compared for gender, age of onset, age of diagnosis, mean blood pressure and estimated glomerular filtration rate (GFR at diagnosis and follow-up, proteinuria, clinical presentation and prognosis.RESULTS: The most common complaint of the patients at presentation was hematuria. The most common histopathological renal finding was the proliferation of mesengial cells in varying degrees. Statistically no significant differences of mean blood pressure, GRF changes, protenuria, clinical findings, and prognosis were detected at presentation and follow-up.CONCLUSION: We could not show short-term effectiveness to predict clinical and laboratory findings, and prognosis of the patients of Oxford classification in children with IgAN.

  5. Cloning and structural analysis of two highly divergent IgA isotypes, IgA1 and IgA2 from the duck billed platypus, Ornithorhynchus anatinus.

    Science.gov (United States)

    Vernersson, M; Belov, K; Aveskogh, M; Hellman, L

    2010-01-01

    To trace the emergence of modern IgA isotypes during vertebrate evolution we have studied the immunoglobulin repertoire of a model monotreme, the platypus. Two highly divergent IgA-like isotypes (IgA1 and IgA2) were identified and their primary structures were determined from full-length cDNAs. A comparative analysis of the amino acid sequences for IgA from various animal species showed that the two platypus IgA isotypes form a branch clearly separated from their eutherian (placental) counterparts. However, they still conform to the general structure of eutherian IgA, with a hinge region and three constant domains. This indicates that the deletion of the second domain and the formation of a hinge region in IgA did occur very early during mammalian evolution, more than 166 million years ago. The two IgA isotypes in platypus differ in primary structure and appear to have arisen from a very early gene duplication, possibly preceding the metatherian eutherian split. Interestingly, one of these isotypes, IgA1, appears to be expressed in only the platypus, but is present in the echidna based on Southern blot analysis. The platypus may require a more effective mucosal immunity, with two highly divergent IgA forms, than the terrestrial echidna, due to its lifestyle, where it is exposed to pathogens both on land and in the water. PMID:19913303

  6. Linear IgA Bullous Dermatosis

    DEFF Research Database (Denmark)

    Lings, Kristina; Bygum, Anette

    2015-01-01

    Linear IgA bullous dermatosis (LAD) is an autoimmune, chronic bullous disease affecting primarily young children and adults. Studies on LAD are relatively sparse and from Scandinavia we could only find a few case reports. Therefore we decided to conduct a retrospective investigation of patients...

  7. IgA Antibodies in Rett Syndrome

    Science.gov (United States)

    Reichelt, K. L.; Skjeldal, O.

    2006-01-01

    The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

  8. Kaubamajal iga kuues kroon Kiadelt / Virge Lahe

    Index Scriptorium Estoniae

    Lahe, Virge

    2007-01-01

    Tallinna Kaubamaja kontserni müügitulust moodustas 2007. aasta esimesel poolel suure osa Kia mudelite müük Baltimaades. Diagramm: Tallinna Kaubamaja käive kolmekordistunud; Iga kuues kroon autode müügist. Vt. samas: Analüütik: Kaubamaja aktsiat tasub osta

  9. Structure and function relationships in IgA.

    Science.gov (United States)

    Woof, J M; Russell, M W

    2011-11-01

    Immunoglobulin A (IgA) has a critical role in immune defense particularly at the mucosal surfaces, and is equipped to do so by the unique structural attributes of its heavy chain and by its ability to polymerize. Here, we provide an overview of human IgA structure, describing the distinguishing features of the IgA1 and IgA2 subclasses and mapping the sites of interaction with host receptors important for IgA's functional repertoire. Remarkably, these same interaction sites are targeted by binding proteins and proteases produced by various pathogens as a means to subvert the protective IgA response. As interest in the prospect of therapeutic IgA-based monoclonal antibodies grows, the emerging understanding of the relationship between IgA structure and function will be invaluable for maximizing the potential of these novel reagents. PMID:21937984

  10. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

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

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of...... clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment. 6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion that...... lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  11. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

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

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of...... lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  12. Renal function in diabetic nephropathy.

    Science.gov (United States)

    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  13. Saliva and sera IgA and IgG in Egyptian Giardia-infected children.

    Science.gov (United States)

    El-Gebaly, Naglaa Saad M; Halawa, Eman Fawzy; Moussa, Hanaa M Ezzat; Rabia, Ibrahim; Abu-Zekry, Maha

    2012-08-01

    Giardiasis is a gastrointestinal infection of wide distribution that is more prevalent in childhood. Easy and rapid diagnosis of giardiasis is essential for reduction of this infection. This cross-sectional study included 62 children in which collection of saliva, stool and serum samples was performed. An enzyme-linked immunosorbent assay (ELISA) technique was evaluated to detect IgA and IgG responses in both saliva and serum samples. Twenty-two children were positive for Giardia duodenalis infection by direct examination of faecal specimens, 20 non-infected and 20 infected with other parasites. Salivary and serum IgA and IgG responses against G. duodenalis infection were significantly higher in Giardia parasitized than non-Giardia parasitized children (p < 0.001). This concludes that specific salivary IgA may serve as a diagnostic tool and specific salivary IgG as a screening tool in monitoring the exposure of various populations to Giardia duodenalis. The advantage of salivary assays over serum immunoglobulin assay is being easy and non-invasive in sampling technique which is important especially for young children. PMID:22402609

  14. Association of genetic variants with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Saliha; Rizvi; Syed; Tasleem; Raza; Farzana; Mahdi

    2014-01-01

    Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

  15. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR;

    2000-01-01

    melaninogenica, Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required...

  16. Explanatory style and Immunoglobulin A (IgA).

    Science.gov (United States)

    Brennan, F X; Charnetski, C J

    2000-01-01

    The construct of explanatory style has been related to numerous aspects of human psychology, including health. Our research has focused on the effects of various psychological variables on the immune system, in particular Immunoglobulin A (IgA). We had participants fill out the Attributional Style Questionnaire (ASQ), the predominant measure of explanatory style, and assayed saliva samples for secretory IgA. No relationship was observed between overall ASQ score and IgA, or composite optimism score and IgA. However, we observed significant negative correlations between both the composite pessimism score and IgA, as well as the hopelessness score and IgA. Pessimistic explanatory style may therefore be related to immune system deficits and poor health. PMID:11330488

  17. TCM Differential Treatment of IgA Nephrosis

    Institute of Scientific and Technical Information of China (English)

    聂莉芳

    2005-01-01

    @@ IgA nephrosis, with an incidence of 38%-49% in the primary glomerulopathy in China, is one of the main causes for the late renal failure. In view of the fact that there are no specific Western remedies for IgA nephrosis characterized by hematuria, the researches on TCM differential treatment of IgA nephrosis have been listed in the major projects of "the Scientific Technologies in thel0th 5-year plan of China".

  18. Sonographic findings in Gouty Nephropathy

    International Nuclear Information System (INIS)

    Ultrasound(US) findings of hyperechoic renal medulla in gouty nephropathy were compared with clinical features such as serum uric acid level to evaluate its usefulness in determination of the treatment and prognosis. A retrospective review of US of 36 cases of qouty arthritis was classified into four groups according to the medullary echogenicity (O :normal, grade I: renal medulla as isoechoic as renal cortex, grade II; heterogeneous increased echogenicity of renal medulla than that of renal cortex, grade III: the echogenicity of all renal medulla higher than that of renal cortex with renal contour deformity) which were compared with the serum urate level and associated conditions. Nephrocalcinosis and nephrolithiasis were analyzed through the KUB and the RGB. The degree of hyperechoic renal medulla was related to the level of serum uric acid, and in group IV, six cases of obstructive uropathy (nephrocalcinosis and nephrolithiasis) showed deformed renal contour. Associated conditions such as hypertension, alcoholism, diabetes mellitus and drug abuse were distributed in relation to the degree of hyperechoic renal medullas. US findings of hyperechoic renal mebulla was related with uric acid level in gouty nephropathy and thus could be valuable for treatment decision and prediction of prognosis

  19. Sonographic findings in Gouty Nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Jeon, Woo Ki; Kim, Ho Kyun; Kim, Yong Soo; Han, Chang Yul; Kim, Young Tong; Han, Sung Tag; Lee, Yoon Woo [Inje University College of Medicine, Seoul (Korea, Republic of)

    1994-09-15

    Ultrasound(US) findings of hyperechoic renal medulla in gouty nephropathy were compared with clinical features such as serum uric acid level to evaluate its usefulness in determination of the treatment and prognosis. A retrospective review of US of 36 cases of qouty arthritis was classified into four groups according to the medullary echogenicity (O :normal, grade I: renal medulla as isoechoic as renal cortex, grade II; heterogeneous increased echogenicity of renal medulla than that of renal cortex, grade III: the echogenicity of all renal medulla higher than that of renal cortex with renal contour deformity) which were compared with the serum urate level and associated conditions. Nephrocalcinosis and nephrolithiasis were analyzed through the KUB and the RGB. The degree of hyperechoic renal medulla was related to the level of serum uric acid, and in group IV, six cases of obstructive uropathy (nephrocalcinosis and nephrolithiasis) showed deformed renal contour. Associated conditions such as hypertension, alcoholism, diabetes mellitus and drug abuse were distributed in relation to the degree of hyperechoic renal medullas. US findings of hyperechoic renal mebulla was related with uric acid level in gouty nephropathy and thus could be valuable for treatment decision and prediction of prognosis.

  20. Significance of unilateral radiation nephropathy

    International Nuclear Information System (INIS)

    Thirteen patients with non-Hodgkin's lymphoma with residual disease in the abdomen were treated by irradiation to the whole abdomen and left upper quadrant. The entire or half of the left kidney received between 2550 rad in 6 weeks and 4900 rad in 5 weeks. Seven of 12 patients evaluated showed functional and/or morphological changes in the left kidney on renal function studies and renal scan at various intervals. None of these patients clinically demonstrated overt acute radiation nephropathy. Three patients developed elevated blood pressure; the plasma renin level was markedly elevated in one of these patients. With the possible exception of one patient, no patient was discovered to have any functional morphological changes in the right kidney. The lymphoma in the abdomen was under control in 12 out of 13 patients treated at this writing

  1. BIOCHEMICAL SCREENING OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Vivek

    2016-01-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by the following- Persistent albuminuria (>300mg/d or >200μg/min, that is confirmed on at least 2 occasions 3-6 months apart diabetic, progressive decline in the Glomerular Filtration Rate (GFR, elevated arterial blood pressure. The earliest biochemical criteria for the diagnosis of diabetic nephropathy is the presence of micro-albumin in the urine, which if left untreated will eventually lead to End-Stage Renal Disease (ESRD. Micro-albuminuria refers to the excretion of albumin in the urine at a rate that exceeds normal limits. The current study was conducted to establish the prevalence of micro-albuminuria in a sequential sample of diabetic patients attending hospital and OPD Clinic to determine its relationship with known and putative risk factors to identify micro- and normo-albuminuric patients in their sample for subsequent comparison in different age, sex, weight and creatinine clearance of the micro- and normo-albuminuric patients. This cross-sectional analytical study was conducted in one hundred patients at Saraswathi Institute of Medical Sciences, Anwarpur, Hapur, U. P. Patients having diabetes mellitus in different age group ranging from 30 to 70 years were selected. Data was analysed by SPSS software. Micro-albuminuria was observed in 35% in patients with type 2 diabetes mellitus. It was observed that 65% patients were free from any type of albuminuria. Also micro-albuminuria was present in 10% of the patients less than 50 yrs. of age, while 15% of the patients more than 50 yrs. of age were having micro-albuminuria. There was a statistically significant correlation of micro-albuminuria with duration of diabetes. Incidence of micro-albuminuria increases with age as well as increased duration of diabetes mellitus. Our study shows that only 5% patients developed macro-albuminuria. Glycosylated haemoglobin and fasting plasma glucose was significantly raised among all these

  2. Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae.

    Science.gov (United States)

    Lomholt, H; Poulsen, K; Kilian, M

    1995-02-01

    Cloning and sequencing of the IgA1 protease gene (iga) from Neisseria meningitidis strain HF13 showed an overall structure equivalent to iga genes from Neisseria gonorrhoeae and Haemophilus influenzae, although no region corresponding to the gonococcal alpha-peptide was evident. An additional 18 N. meningitidis and 3 H. influenzae iga genes were amplified by the polymerase chain reaction technique and sequenced corresponding approximately to the N-terminal half of the mature enzyme. Comparative analyses of a total of 29 iga genes showed that pathogenic Neisseria have iga genes with a significantly lower degree of heterogeneity than H. influenzae iga genes. Recombinational events indicated by mosaic-like structures corresponding to those found among N. gonorrhoeae protease genes were detected among N. meningitidis iga genes. One region showed characteristic differences in sequence and length which correlated with each of the different cleavage specificities. Meningococci were extremely conserved in this region with no evidence of recombination between isolates of different cleavage specificities. Sequences further downstream showed no obvious relationship with enzyme cleavage type. This region consisted of conserved areas interspersed with highly variable areas. Amino acid sequence homologies in the variable regions of meningococci reflected the antigenic types defined by using polyclonal neutralizing antibodies. PMID:7783620

  3. Phase Field Modeling Using PetIGA

    KAUST Repository

    Vignal, Philippe A.

    2013-06-01

    Phase field modeling has become a widely used framework in the computational material science community. Its ability to model different problems by defining appropriate phase field parameters and relating it to a free energy functional makes it highly versatile. Thermodynamically consistent partial differential equations can then be generated by assuming dissipative dynamics, and setting up the problem as one of minimizing this free energy. The equations are nonetheless challenging to solve, and having a highly efficient and parallel framework to solve them is necessary. In this work, a brief review on phase field models is given, followed by a short analysis of the Phase Field Crystal Model solved with Isogeometric Analysis us- ing PetIGA. We end with an introduction to a new modeling concept, where free energy functions are built with a periodic equilibrium structure in mind.

  4. The influences of hinge length and composition on the susceptibility of human IgA to cleavage by diverse bacterial IgA1 proteases.

    Science.gov (United States)

    Senior, Bernard W; Woof, Jenny M

    2005-06-15

    The influences of IgA hinge length and composition on its susceptibility to cleavage by bacterial IgA1 proteases were examined using a panel of IgA hinge mutants. The IgA1 proteases of Streptococcus pneumoniae, Streptococcus sanguis strains SK4 and SK49, Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae cleaved IgA2-IgA1 half hinge, an Ab featuring half of the IgA1 hinge incorporated into the equivalent site in IgA1 protease-resistant IgA2, whereas those of Streptococcus mitis, Streptococcus oralis, and S. sanguis strain SK1 did not. Hinge length reduction by removal of two of the four C-terminal proline residues rendered IgA2-IgA1 half hinge resistant to all streptococcal IgA1 metalloproteinases but it remained sensitive to cleavage by the serine-type IgA1 proteases of Neisseria and Haemophilus spp. The four C-terminal proline residues could be substituted by alanine residues or transferred to the N-terminal extremity of the hinge without affect on the susceptibility of the Ab to cleavage by serine-type IgA1 proteases. However, their removal rendered the Ab resistant to cleavage by all the IgA1 proteases. We conclude that the serine-type IgA1 proteases of Neisseria and Haemophilus require the Fab and Fc regions to be separated by at least ten (or in the case of N. gonorrhoeae type I protease, nine) amino acids between Val(222) and Cys(241) (IgA1 numbering) for efficient access and cleavage. By contrast, the streptococcal IgA1 metalloproteinases require 12 or more appropriate amino acids between the Fab and Fc to maintain a minimum critical distance between the scissile bond and the start of the Fc. PMID:15944283

  5. Exposures influencing total IgA level in colostrum.

    Science.gov (United States)

    Munblit, D; Sheth, S; Abrol, P; Treneva, M; Peroni, D G; Chow, L-Y; Boner, A L; Pampura, A; Warner, J O; Boyle, R J

    2016-02-01

    Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, Pcolostrum collection time (Pcolostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries. PMID:26387688

  6. Cancer risk after cyclophosphamide treatment in idiopathic membranous nephropathy

    NARCIS (Netherlands)

    Brand, J.A. van den; Dijk, P.R. van; Hofstra, J.M.; Wetzels, J.F.

    2014-01-01

    BACKGROUND AND OBJECTIVES: Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer

  7. IgA in the horse: cloning of equine polymeric Ig receptor and J chain and characterization of recombinant forms of equine IgA

    OpenAIRE

    Lewis, M J; Wagner, B.; Irvine, R M; Woof, J.M.

    2010-01-01

    As in other mammals, immunoglobulin A (IgA) in the horse has a key role in immune defense. To better dissect equine IgA function, we isolated complementary DNA (cDNA) clones for equine J chain and polymeric Ig receptor (pIgR). When coexpressed with equine IgA, equine J chain promoted efficient IgA polymerization. A truncated version of equine pIgR, equivalent to secretory component, bound with nanomolar affinity to recombinant equine and human dimeric IgA but not with monomeric IgA from eithe...

  8. Signaling pathways in diabetic nephropathy.

    Science.gov (United States)

    Kawanami, Daiji; Matoba, Keiichiro; Utsunomiya, Kazunori

    2016-10-01

    Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD), however, specific treatment for DN has not yet been elucidated. Therefore, it is critically important to understand the molecular mechanism underlying DN to develop cause-related therapeutic strategy. To date, various factors such as hemodynamic changes and metabolic pathways have been shown to be involved in the pathogenesis of DN. Excessive glucose influx activates cellular signaling pathways, including the diacylglycerol (DAG)-protein kinase C (PKC) pathway, advanced glycation end-products (AGE), polyol pathway, hexosamine pathway and oxidative stress. These factors interact with one another, thereby facilitating inflammatory processes, leading to the development of glomerulosclerosis under diabetic conditions. In addition to metabolic pathways, Rho-kinase, an effector of small-GTPase binding protein Rho, has been implicated as an important factor in the pathogenesis of DN. A number of studies have demonstrated that Rho-kinase plays key roles in the development of DN by inducing endothelial dysfunction, mesangial excessive extracellular matrix (ECM) production, podocyte abnormality, and tubulointerstitial fibrosis. In this review article, we describe our current understanding of the signaling pathways in DN. PMID:27094540

  9. [Scarring linear IgA dermatosis in the adult].

    Science.gov (United States)

    Kurz, K; Mahrle, G

    1986-10-15

    A 54-year-old woman had a six-months history of a scarring blistering disease with clinical signs of dermatitis herpetiformis and bullous pemphigoid. Direct immunofluorescence examination showed homogeneously linear deposits of IgA along the dermo-epidermal junction. Electron microscopic studies revealed blistering above and beneath the lamina densa. Referring to this new case of a scarring linear IgA disease we discuss some other forms of scarring bullous diseases in adults. PMID:3541412

  10. The gastrointestinal frontier: IgA and viruses

    Directory of Open Access Journals (Sweden)

    Margaret E. Conner

    2013-11-01

    Full Text Available Viral gastroenteritis is one of the leading causes of diseases that kill approximately 2.2 million people world wide each year. IgA is one of the major immune effector products present in the gastrointestinal tract yet its importance in protection against gastrointestinal viral infections has been difficult to prove. In part this has been due to a lack of small and large animal models in which pathogenesis of and immunity to gastrointestinal viral infections is similar to that in humans. Much of what we have learned about the role of IgA in the intestinal immune response has been obtained from experimental animal models of rotavirus infection. Rotavirus-specific intestinal IgA appears to be one of the principle effectors of long term protection against rotavirus infection. Thus, there has been a focus on understanding the immunological pathways through which this virus specific IgA is induced during infection. In addition, the experimental animal models of rotavirus infection provide excellent systems in which new areas of research on viral-specific intestinal IgA including the long term maintenance of viral-specific IgA.

  11. Treatment of Diabetic Nephropathy with Acupuncture

    Institute of Scientific and Technical Information of China (English)

    CHU Qin; WANG Lin; LIU Guo-zhen; HAN Chou-ping

    2007-01-01

    Objective: to observe the clinical efficacy of acupuncture on diabetic nephropathy.Methods: altogether 54 cases were randomly allocated into acupuncture group (30 cases) and control group of western medications (24 cases), the latter was treated with routine western medication, while the former was combined acupuncture based on routine western medication,and the treatment course of the two groups were both 30 days. Results: the effect of treatment group was superior to the control group (P<0.05). Conclusion: acupuncture can improve symptoms of diabetic nephropathy, lower blood glucose, urine albumin, blood urine nitrogen,and creatinine and improve the function of kidney.

  12. Metabolic Syndrome in IgA Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Kati Kaartinen

    2014-08-01

    Full Text Available Background/Aims: Metabolic syndrome (MetS may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN and its impact on disease progression in a retrospective fashion. Patients and Methods: Altogether, 174 subjects (104 males were examined 11 years (first visit after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded. Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol constitutes the diagnosis. Results: The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. Conclusion: The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable.

  13. Metabolic Syndrome in IgA Glomerulonephritis

    Science.gov (United States)

    Kaartinen, Kati; Syrjänen, Jaana; Pörsti, Ilkka; Harmoinen, Aimo; Huhtala, Heini; Mustonen, Jukka

    2014-01-01

    Background/Aims Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Patients and Methods Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. Results The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. Conclusion The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable. PMID:25337083

  14. Antigenic heterogeneity of IgA anti-GBM disease: new renal targets of IgA autoantibodies.

    Science.gov (United States)

    Ho, Julie; Gibson, Ian W; Zacharias, James; Fervenza, Fernando; Colon, Selene; Borza, Dorin-Bogdan

    2008-10-01

    Anti-glomerular basement membrane (anti-GBM) disease is an aggressive form of glomerulonephritis, usually mediated by immunoglobulin G (IgG) autoantibodies to the noncollagenous (NC1) domain of alpha 3(IV) collagen. Less is known about the target antigen(s) in patients with atypical anti-GBM disease involving IgA autoantibodies. We report a new case of IgA anti-GBM disease in a patient with a history of proliferative lupus nephritis who presented with increasing creatinine levels, proteinuria, and hematuria, but no clinical or serological evidence of lupus recurrence. Renal biopsy showed focal and segmental necrotizing glomerulonephritis with strong linear capillary loop IgA staining by means of immunofluorescence. Serological test results were negative for IgG or IgA autoantibodies against the alpha 3NC1 domain. By means of immunoblotting, IgA from patient serum bound to 38- to 48-kd antigens collagenase-solubilized from human GBM, but not to purified NC1 domains of GBM collagen IV. The target of patient's IgA autoantibodies thus was identified as a novel GBM antigen, distinct from the alpha 3NC1 domain or other known targets of anti-GBM IgA autoantibodies. Clinical resolution was attained by means of conventional treatment with steroids and cyclophosphamide. The diversity of antigens recognized by anti-GBM IgA autoantibodies highlights the importance of renal biopsy for the reliable diagnosis of this rare condition because conventional serological immunoassays likely would yield false-negative results. PMID:18752876

  15. Vesicoureteral reflux and reflux nephropathy

    International Nuclear Information System (INIS)

    Vesicoureteral reflux (VUR) is mainly a primary phenomenon due to incompetence of the ureterovesical junction, mostly affecting a pediatric population. During micturition cystourethrography (MCU) reflux into the kidney - intrarenal reflux (IRR) - is occasionally seen. In areas with IRR the kidney surface may subsequently be depressed and the papillae retracted (reflux nephropathy (RN)). VUR may lead to hypertension and/or end-stage renal failure. Most commonly, VUR is discovered during evaluation for urinary tract infection, but it may also be present in patients with hypertension, toxemia of pregnancy, chronic renal failure and proteinuria, and it may be found in siblings of patients with VUR. For the time being VUR is demonstrated at radiographic MCU, whereas RN is diagnosed by demonstration of focal scars and of abnormal parenchymal thickness at urography. In children with VUR and no abnormalities of calyces or parenchymal defects standardized measurement of the parenchymal thickness at three sites may identify kidneys which are likely to develop focal scars. Quantitation of focal scarring should be performed in connection with a measure of the overall kidney size. The occurrence of IRR is dependent of the papillary morphology, intrapelvic pressure and urine flow. There may be an important relationship between renal ischemia and IRR in producing a 'vicious circle of deleterious effects' which, combined with parenchymal extravasation, may lead to RN. Treatment of VUR includes medical and surgical management. Since renal scarring may occur in infancy, prevention should focus on infants and young children. Infants and young children with severe VUR may have normal urograms. Therefore a MCU should also be performed, preferably with the recommended standardized technique. (orig.)

  16. Monitoring Diabetic Nephropathy by Circulating Gangliosides.

    Science.gov (United States)

    Ene, Corina Daniela; Penescu, Mircea; Anghel, Amalia; Neagu, Monica; Budu, Vlad; Nicolae, Ilinca

    2016-01-01

    Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria. PMID:26359623

  17. Diabetic nephropathy: Prescription trends in tertiary care

    Directory of Open Access Journals (Sweden)

    Devi D

    2008-01-01

    Full Text Available Diabetic nephropathy is a leading cause of end stage renal disease. Drug utilization studies could promote rational drug use. The objective of this study was to evaluate prescribing trends in hospitalized patients with diabetic nephropathy. A prospective, observational study was conducted in a tertiary care hospital. The demographic, disease and treatment data of patients with diabetic nephropathy were collected for a period of six months and analysed. Drugs were classified using World Health Organization recommended Anatomic Therapeutic Chemical classification. A total of 755 drugs (7.4 drugs per prescription were prescribed to 102 study patients, who were all hypertensive and in late stages of diabetic nephropathy. Drug classes with largest representation were those acting on gastrointestinal tract plus metabolism (37% and cardiovascular drugs (28%. Calcium channel blockers represented the largest antihypertensive drug class (41%. Almost three-fourths of patients received more than one antihypertensive agent. Approximately 37% of patients did not receive any antidiabetic medication. Of those who did, prescriptions for insulin (91% exceeded those of oral hypoglycaemic drugs (9%. Antimicrobials accounted for 10.2% of all drugs prescribed, of which 31.8% were quinolones. Drugs prescribed by generic name accounted for 11.98%. While all patients received antihypertensive therapy, more than a third were not on any antidiabetic treatment. Antihypertensive poly-therapy was observed in the majority with calcium channel blockers being most frequently prescribed antihypertensive drug class. Insulin was the preferred to hypoglycaemic drugs.

  18. Application of bioeffect to clinical radiation nephropathy

    International Nuclear Information System (INIS)

    Normal tissue injury is usually the dose limiting factor in radiotherapy. It is, therefore, important to gain information on the tolerance of normal tissues to radiation and on the sensitivity to fractionation of the total radiation dose. The aim of the present study was to correlate prognostic factors with clinical radiation nephropathy

  19. The course of incipient diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    1985-01-01

    With the aim of defining the transitional phase from normal or near normal albumin excretion to overt diabetic nephropathy, 23 male diabetics of more than 7 years' duration, below 40 years of age and a baseline urinary albumin excretion above 15 micrograms/min but without clinical proteinuria (in...

  20. Development of ASSURE® Dengue IgA Rapid Test for the Detection of Anti-dengue IgA from Dengue Infected Patients

    OpenAIRE

    Yun Ying Tan; Sekaran, Shamala D.; Seok Mui Wang; Firoz Ahmed; Anowar Hossain; Bijon Kumar Sil

    2011-01-01

    Background: Rapid and early dengue diagnosis is essential for patient management and early disease intervention. MP Diagnostics ASSURE® Dengue IgA Rapid Test (Dengue IgA RT) was developed for the rapid detection of anti-dengue IgA in patients′ biological samples. The performance of Dengue IgA RT was examined using multiple categories of well-characterized samples. Materials and Methods: Dengue IgA RT was designed and developed. Following characterization of samples by reference ELISAs, the pe...

  1. Recombinant human immunoglobulin (Ig)A1 and IgA2 anti-D used for detection of IgA deficiency and anti-IgA

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Dziegiel, Morten Hanefeld

    2008-01-01

    To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA....

  2. Sites in the CH3 domain of human IgA1 that influence sensitivity to bacterial IgA1 proteases.

    Science.gov (United States)

    Senior, Bernard W; Woof, Jenny M

    2006-09-15

    The influence of regions, other than the hinge, on the susceptibility of human IgA1 to cleavage by diverse bacterial IgA1 proteases, was examined using IgA1 mutants bearing amino acid deletions, substitutions, and domain swaps. IgA1 lacking the tailpiece retained its susceptibility to cleavage by all of the IgA1 proteases. The domain swap molecule alpha1alpha2gamma3, in which the CH3 domain of IgA1 was exchanged for that of human IgG1, was resistant to cleavage with the type 1 and 2 serine IgA1 proteases of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae, but remained sensitive to cleavage with the metallo-IgA1 proteases of Streptococcus pneumoniae, Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis. Substitution of the IgA1 Calpha3 domain motif Pro440 -Phe443 into the corresponding position in the Cgamma3 domain of alpha1alpha2gamma3 resulted now in sensitivity to the type 2 IgA1 protease of N. meningitidis, indicating the possible requirement of these amino acids for sensitivity to this protease. For the H. influenzae type 2 protease, resistance of an IgA1 mutant in which the CH3 domain residues 399-409 were exchanged with those from IgG1, but sensitivity of mutant HuBovalpha3 in which the Calpha3 domain of bovine IgA replaces that of human IgA1, suggests that CH3 domain residues Glu403, Gln406, and Thr409 influence sensitivity to this enzyme. Hence, unlike the situation with the metallo-IgA1 proteases of Streptococcus spp., the sensitivity of human IgA1 to cleavage with the serine IgA1 proteases of Neisseria and Haemophilus involves their binding to different sites specifically in the CH3 domain. PMID:16951354

  3. Serum IL-18 Is Closely Associated with Renal Tubulointerstitial Injury and Predicts Renal Prognosis in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Beili Shi

    2012-01-01

    Methods. Serum IL-18 levels in 76 IgAN patients and 36 healthy blood donors were measured by ELISA. We evaluated percentage of global and segmental sclerosis (GSS and extent of tubulointerstitial damage (TID. The correlations between serum IL-18 levels with clinical, histopathological features and renal prognosis were evaluated. Results. The patients were 38.85±10.95 years old, presented with 2.61 (1.43∼4.08 g/day proteinuria. Serum IL-18 levels were significantly elevated in IgAN patients. Baseline serum IL-18 levels were significantly correlated with urinary protein excretion (r=0.494, P=0.002, Scr (r=0.61, P<0.001, and eGFR (r=−0.598, P<0.001. TID scores showed a borderline significance with serum IL-18 levels (r=0.355, P=0.05. During follow-up, 26 patients (34.21% had a declined renal function. Kaplan-Meier analysis found those patients with elevated IL-18 had a significant poor renal outcome (P=0.03, and Cox analysis further confirmed that serum IL-18 levels were an independent predictor of renal prognosis (β=1.98, P=0.003.

  4. IgA Nephropathy: A Rare Lesion in Renal Biopsy in Systemic Lupus Erythematosus: Case Reports and Review of Literature

    OpenAIRE

    Gürsel YILDIZ; Emre ÇİÇEKLİ; Kayataş, Mansur; Yilmaz, Abdulkerim; Ferhan CANDAN

    2013-01-01

    Lupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus (SLE). Lupus nephritis is a frequent complication of SLE that increases mortality and morbidity. Minimal glomerular lesions, mesangial proliferative, focal proliferative, membranous and diffuse glomerulonephritis can be seen in renal biopsies of patients with lupus nephritis. It has been reported that non-lupus nephritis can also rarely occur in SLE. While non-lupus nephritis cases usually manifest as foca...

  5. Combination regimen of leflunomide plus methylprednisolone in a female patient with reactive arthritis and concomitant IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-zhi; ZHAO Xue-zhi; WU Jun; MEI Chang-lin

    2010-01-01

    @@ Spondyloarthropathies (SpAs) include five categories: ankylosing spondylitis (AS),1 reactive arthritis (ReA), psoriatic arthritis (PsA), enteropathic arthritis (EA) and undifferentiated spondyloarthropathy (USpA).~2 ReA is an aseptic arthritis occurring after extra-articular infections, particularly genitourinary (GU) or gastrointestinal (GI) tracts. When arthritis is accompanied by conjunctivitis and urethritis, the diagnosis of Reiter syndrome will be suitable for this clinical triad; however, the term "ReA" has been proposed to substitute for Reiter syndrome.

  6. Isogeometric Analysis of Hyperelastic Materials Using PetIGA

    KAUST Repository

    Bernal, L.M.

    2013-06-01

    In this work different nonlinear hyperelastic models for slightly compressible materials are implemented in an isogeometric finite element model. This is done within the recently developed computational framework called PetIGA, which uses isoge- ometric analysis and modern computational tools to solve systems of equations directly and iteratively. A flexible theoretical background is described to implement other hyperelastic models and possibly transient problems in future work. Results show quadratic convergence of the nonlinear solution consistent with the Newton-Raphson method that was used. Finally, PetIGA proves to be a powerful and versatile tool to solve these types of problems efficiently.

  7. Genetic associations in diabetic nephropathy: a meta-analysis

    OpenAIRE

    Mooyaart, A. L.; Valk, E. J. J.; L. A. van Es; Bruijn, J. A.; de Heer, E.; Freedman, B.I.; Dekkers, O. M.; Baelde, H. J.

    2010-01-01

    Aims/hypothesis This meta-analysis assessed the pooled effect of each genetic variant reproducibly associated with diabetic nephropathy. Methods PubMed, EMBASE and Web of Science were searched for articles assessing the association between genes and diabetic nephropathy. All genetic variants statistically associated with diabetic nephropathy in an initial study, then independently reproduced in at least one additional study, were selected. Subsequently, all studies assessing these variants we...

  8. Tubular biomarkers to assess progression of diabetic nephropathy.

    Science.gov (United States)

    Tramonti, Gianfranco; Kanwar, Yashpal S

    2011-05-01

    Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy. However, Nielsen et al. report a lack of an independent correlation between these biomarkers and glomerular filtration rate. Therefore, these markers seem to offer no improvement in the management of diabetic nephropathy. PMID:21527942

  9. Experimental cholestasis promotes the deposition of glomerular IgA immune complexes.

    OpenAIRE

    Emancipator, S. N.; Gallo, G. R.; Razaboni, R.; Lamm, M. E.

    1983-01-01

    Previous experimental and clinical studies support a role for the hepatobiliary system in the clearance of oligomeric IgA from serum, and alterations of this system have been associated with the deposition of IgA in the renal mesangium. The present studies in mice address the question of whether the mesangial deposition of IgA following cholestasis includes immune complexes. While bile duct ligation resulted in mesangial IgA deposition within several days in approximately 75% of animals, whet...

  10. Diabetic Nephropathy : Evaluation with Doppler Ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Jung Suk; Kim, Seung Hyup; Kang, Heung Sik; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1996-06-15

    To compare Doppler ultrasonography with laboratory tests in evaluation of diabetic nephropathy. Fifty-five patients (mean age = 60, M : F = 26 : 29) with diabetes mellitus underwent renal Doppler ultrasonography. Resistive indices were compared with degree of proteinuria, serum creatinine level, and creatinine clearance rate. Eighteen patients who showed no proteinuria or microscopic proteinuria had a mean resistive index (RI) of 0.72 (SD, 0.05), 16 patients with macroscopic proteinuria without nephrotic syndrome had a mean RI of 0.82 (SD, 0.13), and 21 patients with nephrotic syndrome had a mean RI of 0.90 (SD, 0.12). Renal RI correlated highly with serum creatinine level (r = 0.62) and creatinine clearance rate (r = -0.43). Renal Doppler ultrasonography provides a useful indication of renal function in diabetic nephropathy but cannot offer an advantage over conventional laboratory test

  11. Alteration of pulmonary function in diabetic nephropathy

    OpenAIRE

    Shafiee, Gita; Khamseh, Mohammad E.; Rezaei, Nader; Aghili, Rokhsareh; MALEK, Mojtaba

    2013-01-01

    Background Type 2 diabetes mellitus is increasing worldwide with an alarming rate. It is associated with the development of various chronic complications. The aim of this study was to explore the alteration of pulmonary function, and its association with renal complications in people with type 2 diabetes mellitus. Methods This cross-sectional study was conducted on three groups; 40 diabetic subjects without nephropathy (urinary albumin300 mg/day) .Diabetic subjects were matched to the control...

  12. Biomarkers for early detection of sickle nephropathy

    OpenAIRE

    Sundaram, Nambirajan; Bennett, Michael; Wilhelm, Jamie; Kim, Mi-Ok; Atweh, George; Devarajan, Prasad; Malik, Punam

    2011-01-01

    Renal complications affect nearly 30–50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, noninvasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for n...

  13. Contrast-induced nephropathy: risks, pathogenetic, prevention

    International Nuclear Information System (INIS)

    Full text: The aim of the presentation is to review the contrast induced nephropathy ? nature, mechanisms of development, risk factors. Summary of the most important ways of prevention, diagnostics and treatment. The definition of CIN according the European Association of Urogenital Radiology is: 'A condition, in which renal function is impaired (elevation of serum creatinine with more than 25% or 44 μmol/l above the initial level) due to intravasal application of contrast media (CM) within 3 days following the application and when no other etiology factors are present'. We summarize the main risk factors of developing CIN - renal failure, diabetic nephropathy, dehydration, congestive heart failure, high blood pressure, age above 70 yrs, nephrotoxic medicines. The most effective ways of preventing CIN are the good hydratation of the patients and the usage of low-osmolar or iso-osmolar CM. Therapeutic treatment is with no proven preventive effect and currently is not routinely recommended. An early hem dialysis does not decrease the risk level of CIN development in patients with chronic renal failure (CRF). In such patients complete elimination of CM is achieved only after several hem dialyses. Hem filtration reliably decreases the risk of CIN in CRF patients, but is expensive and not widely available. We present a case from our hospital of a patient with diabetic nephropathy, who developed CIN following a coronary angiography

  14. Abortide arv kahaneb Eestis iga aastaga / Rebekka Lotman

    Index Scriptorium Estoniae

    Lotman, Rebekka, 1978-

    2005-01-01

    Vt. ka Zdorovje dlja Vsehh 2005 märts, lk. 6. Kuigi abortide arv väheneb Eestis iga aastaga, tuleb naistearstide hinnangul oodata veel kümmekond aastat, et see langeks sama madalale tasemele nagu Põhjamaades. Lisaks diagramm abortide arvu kohta 1991-2004

  15. Streikijate armee paisub iga päevaga / Aivar Reinap

    Index Scriptorium Estoniae

    Reinap, Aivar, 1968-

    2004-01-01

    23. septembril alanud raudteetöötajate streigist osavõtjate arv kasvab iga päevaga, kaubarongid veel liiguvad, kuid kui vajalikke samme ei astuta, võib kogu rongiliiklus seiskuda. Lisa: Ronge asendavad bussid. Vt. ka: Edelaraudtee rendib streigi ajaks bussid

  16. Diagnostic Significance of Reduced IgA in Children

    Science.gov (United States)

    Nurkic, Jasmina; Numanovic, Fatima; Arnautalic, Lejla; Tihic, Nijaz; Halilovic, Dzenan; Jahic, Mahira

    2015-01-01

    Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. At the University Clinical Center Tuzla, children with suspected deficient immune response due to reduced values of IgA, goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. Material and methods: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. Conclusion: The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof. PMID:26543309

  17. Childhood Leukemia

    Science.gov (United States)

    ... cells. It is the most common type of childhood cancer. Your blood cells form in your bone ... in the bones or joints Risk factors for childhood leukemia include having a brother or sister with ...

  18. Childhood Stress

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy Childhood Stress KidsHealth > For Parents > Childhood Stress Print A A ... and feel stress to some degree. Sources of Stress Stress is a function of the demands placed ...

  19. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases.

    Science.gov (United States)

    Batten, Margaret R; Senior, Bernard W; Kilian, Mogens; Woof, Jenny M

    2003-03-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement for either proline or threonine at residues 227 to 228. By contrast, the IgA1 proteases of Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis had an absolute requirement for proline at 227 but not for threonine at 228, which could be replaced by valine. There was evidence in S. mitis that proteases from different strains may have different amino acid requirements for cleavage. Remarkably, some streptococcal proteases appeared able to cleave the hinge at a distant alternative site if substitution prevented efficient cleavage of the original site. Hence, this study has identified key residues required for the recognition of the IgA1 hinge as a substrate by streptococcal IgA1 proteases, and it marks a preliminary step towards development of specific enzyme inhibitors. PMID:12595464

  20. Development of ASSURE® dengue IgA rapid test for the detection of anti-dengue IgA from dengue infected patients

    Directory of Open Access Journals (Sweden)

    Yun Ying Tan

    2011-01-01

    Full Text Available Background: Rapid and early dengue diagnosis is essential for patient management and early disease intervention. MP Diagnostics ASSURE® Dengue IgA Rapid Test (Dengue IgA RT was developed for the rapid detection of anti-dengue IgA in patients′ biological samples. The performance of Dengue IgA RT was examined using multiple categories of well-characterized samples. Materials and Methods: Dengue IgA RT was designed and developed. Following characterization of samples by reference ELISAs, the performance of the kit was evaluated. Results: The overall sensitivity and specificity of Dengue IgA RT were 86.70% (n=233 and 86.05% (n=681 respectively; in which Dengue IgA RT detected 77.42% primary and 92.86% secondary cases; compared to 70.97% and 72.14% by IgM-Cap ELISA and 89.25% and 20% by Non-Structural Protein 1 (NS1 Ag ELISA respectively. Using 125 paired samples, Dengue IgA RT showed 84.80% sensitivity at acute phase and 99.20% sensitivity at convalescent phase; with 92% specificity at both phases. Dengue IgA RT also demonstrated a consistent performance (sensitivity: 85.53%, specificity: 80% with 76 whole blood samples. In detecting all four serotypes of DENV (n=162, the performance of Dengue IgA RT was comparable with in-house IgM-Cap ELISA. Kinetics of anti-dengue IgA production was elucidated with 42.86% detection level as early as one-two days after fever onset, which increased to 83.33% between five and seven days after fever onset. Conclusion: Dengue IgA RT demonstrated a good performance and is applicable as one of the dengue early diagnostic tools at all levels of health care system.

  1. Childhood Obesity

    OpenAIRE

    Wilkinson, Justine; Howard, Simon

    2014-01-01

    Childhood obesity has important consequences for health and wellbeing both during childhood and also in later adult life. The rising prevalence of childhood obesity poses a major public health challenge in both developed and developing countries by increasing the burden of chronic non-communicable diseases. Despite the urgent need for effective preventative strategies, there remains disagreement over its definition due to a lack of evidence on the optimal cut-offs linking childhood BMI to dis...

  2. Childhood Cancer

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Childhood Cancer KidsHealth > For Parents > Childhood Cancer Print A A A Text Size What's ... in children, but can happen. The most common childhood cancers are leukemia , lymphoma , and brain cancer . As ...

  3. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens;

    2003-01-01

    effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement......The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...

  4. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, BW; Batten, MR; Kilian, Mogens;

    2002-01-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....

  5. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases.

    Science.gov (United States)

    Senior, B W; Batten, M R; Kilian, M; Woof, J M

    2002-08-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases. PMID:12196126

  6. IgA Protease Activity in Haemophilus parasuis in the Absence of a Recognizable IgA Protease Gene

    Science.gov (United States)

    Background. Haemophilus parasuis, the bacterium responsible for Glasser’s disease, is a pathogen of significant concern in modern high-health swine production systems. Little is known regarding the molecular mechanisms of H. parasuis infection. In some Pasteurellaceae species, IgA proteases aid in d...

  7. Purification and characterization of chimeric human IgA1 and IgA2 expressed in COS and Chinese hamster ovary cells.

    Science.gov (United States)

    Morton, H C; Atkin, J D; Owens, R J; Woof, J M

    1993-11-01

    Ag-specific chimeric human IgA molecules, of the two human subclasses, IgA1 and IgA2, have been expressed in two mammalian cell systems. Analysis of the secreted IgA molecules, purified in milligram quantities from stable Chinese hamster ovary transfectants by Ag affinity chromatography, has allowed a direct comparison of the biologic properties of the two subclasses. HPLC gel filtration analysis revealed that in both subclasses, the IgA molecules associate predominantly into dimers. The monomer units are presumed to interact noncovalently, inasmuch as no dimers are evident when the antibodies are subjected to SDS-PAGE. The recombinant antibodies are glycosylated, inasmuch as a lectin blotting procedure revealed that the H chains of both subclasses are recognized by Con A. When subjected to digestion by preparations of IgA1-specific proteases secreted by two pathogenic streptococcal strains, Streptococcus sanguis and Streptococcus oralis, the recombinant IgA molecules behave just as their natural equivalents. Thus, only the chimeric IgA1 molecule is cleaved, with the IgA2 remaining intact. In terms of interaction with natural effector molecules, both recombinant IgA isotypes were shown to interact with Fc alpha receptors on calcitriol-stimulated HL-60 cells with similar affinity, but neither antibody was found to interact with human C1q. The expression system described readily permits manipulation of the human IgA genes, which should lead to a fuller molecular understanding of how this important antibody mediates its function. PMID:8409433

  8. Luo Lingjie's Experience in Treating Chronic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    Cai Min; Yang Yonghe; Luo Lingjie; Duan Shumin

    2008-01-01

    @@ In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.

  9. VANCOMYCIN-INDUCED LINEAR IGA BULLOUS DERMATOSIS WITH ISOMORPHIC RESPONSE

    Directory of Open Access Journals (Sweden)

    Tatsuhiko Mori

    2013-11-01

    Full Text Available Linear IgA bullous dermatosis (LABD is occasionally induced by certain drugs, of which vancomycin is the most common. We herein describe a case of vancomycin-induced LABD on the trunk and extremities. Our case was unique in which tense bulla was induced on the old operation scars. A 92-year-old man developed diffuse erythema and bullas on his trunk and extremities. Also, blister formation was observed on the operation scar on the abdomen. A biopsy specimen showed subepidermal split with neutrophilic and lymphocytic infiltration in the upper dermis. Direct immunofluorescence showed a linear IgA deposition at the basement membrane zone. His skin conditions were improved by stoppage of vancomycin and topical corticosteroids. We should know about the occurrence of LABD in patients under vancomycin treatment.

  10. Isolation and detection of human IgA using a streptococcal IgA-binding peptide.

    Science.gov (United States)

    Sandin, Charlotta; Linse, Sara; Areschoug, Thomas; Woof, Jenny M; Reinholdt, Jesper; Lindahl, Gunnar

    2002-08-01

    Bacterial proteins that bind to the Fc part of IgG have found widespread use in immunology. A similar protein suitable for the isolation and detection of human IgA has not been described. Here, we show that a 50-residue synthetic peptide, designated streptococcal IgA-binding peptide (Sap) and derived from a streptococcal M protein, can be used for single-step affinity purification of human IgA. High affinity binding of IgA required the presence in Sap of a C-terminal cysteine residue, not present in the intact M protein. Passage of human serum through a Sap column caused depletion of >99% of the IgA, and elution of the column allowed quantitative recovery of highly purified IgA, for which the proportions of the IgA1 and IgA2 subclasses were the same as in whole serum. Moreover, immobilized Sap could be used for single-step purification of secretory IgA of both subclasses from human saliva, with a recovery of approximately 45%. The Sap peptide could also be used to specifically detect IgA bound to Ag. Together, these data indicate that Sap is a versatile Fc-binding reagent that may open new possibilities for the characterization of human IgA. PMID:12133959

  11. Diagnostic Significance of Reduced IgA in Children

    OpenAIRE

    Nurkic, Jasmina; Numanovic, Fatima; Arnautalic, Lejla; Tihic, Nijaz; Halilovic, Dzenan; Jahic, Mahira

    2015-01-01

    Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In olde...

  12. Clinical application of urodilatin in Type 2 diabetic nephropathy

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical application of urodilatin (URO) in tubular injury of DM2. Methods: 41 healthy controls, 33 type 2 diabetics without nephropathy, 37 patients with early stage of diabetic nephropathy and 26 patients with clinical diabetic nephropathy were enrolled in the study and categorized into four groups. Urodilatin was measured by radioimmunoassay (RIA). The changes of urodilatin levels among four groups were analyzed, and correlation analyses were performed between urodilatin and urinary micro-albumin/urine creatinine(mA/UCr). The efficiency index of URO were evaluated by receiver operation characteristic (ROC). Results: Compared with those in the controls,diabetics without nephropathy, early stage of diabetic nephropathy and clinical diabetic nephropathy, the urodilatin level decreased significantly in the course of diabetic nephropathy (P<0.001). The value of URO was significantly correlated with mA/UCr (r=-0.626, P<0.01). In early phase of DM2, The area under curve was 0.759. When the cut-off vaule of URO was ≤51.5 pg/ml, The sensitivity and specificity were 67.14% and 70.29%, respectively. Furthermore, Urodilatin had similar diagnosis efficiency with mA/UCr. Conclusion: The decrease of urodilatin level had clinical value in pristine tubular injury of DM2 and can serve as an evaluation parameter. (authors)

  13. Risk factors and management of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Mohamed Akheel Ahmed

    2013-01-01

    Full Text Available To determine the risk factors for nephropathy in diabetic patients and to study the management of diabetic nephropathy (DN, we conducted a hospital-based prospective study in the Internal Medicine department of our hospital on 60 patients with DN and 60 diabetic patients without DN. An odds ratio (OR disclosed the following risk factors: Hypertension (OR = 2.06, family history of diabetes (OR = 1.23, family history of DN (OR = 2.86, uncontrolled hyperglycemia (OR = 11.80, obesity (OR = 1.07, duration of diabetes between 11 and 20 years (OR = 4.69, smoking (OR = 2.79, alcohol consumption (OR = 3.75, other complications (OR = 2.03, lack of physical activity (OR = 1.51 and anemia (OR = 2.29. According to these risk factors, we suggest that improving patient′s knowledge on diabetes and its treatment, life style modifications and aggressive management of the disease may delay the progression of disease to advanced stages.

  14. Minimizing the risk of chronic allograft nephropathy.

    Science.gov (United States)

    Weir, Matthew R; Wali, Ravinder K

    2009-04-27

    Chronic allograft nephropathy, now defined as interstital fibrosis and tubular atrophy not otherwise specified, is a near universal finding in transplant kidney biopsies by the end of the first decade posttransplantation. After excluding death with functioning graft, caused by cardiovascular disease or malignancy, chronic allograft nephropathy is the leading cause of graft failure. Original assumptions were that this was not a modifiable process but inexorable, likely due to past kidney injuries. However, newer understandings suggest that acute or subacute processes are involved, and with proper diagnosis, appropriate interventions can be instituted. Our method involved a review of the primary and secondary prevention trials in calcineurin inhibitor withdrawal. Some of the more important causes of progressive graft deterioration include subclinical cellular or humoral rejection, and chronic calcineurin inhibitor toxicity. Early graft biopsy, assessment of histology, and changes in immunosuppression may be some of the most important measures available to protect graft function. The avoidance of clinical inertia in pursuing subtle changes in graft function is critical. Modification in maintenance immunosuppression may benefit many patients with early evidence of graft deterioration. PMID:19384181

  15. Relationship between E-cadherin and diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    姜洪娟

    2014-01-01

    Objective To identify novel biomarker for diabetic nephropathy(DN)by urinary proteomic methods,and to detect the expression of E-cadherin in urine and renal tissue of patients with DN.Methods Urine samples were collected from 12 cases of type 1 diabetic nephropathy patients(T1DN),12 cases of type 2 diabetic nephropathy patients(T2DN),12 cases of nephritic syndrome patients(NS),and 12 cases of healthy Controls.Comparative proteomic approach of two-dimensional gel electro-

  16. IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches.

    Science.gov (United States)

    Reboldi, Andrea; Arnon, Tal I; Rodda, Lauren B; Atakilit, Amha; Sheppard, Dean; Cyster, Jason G

    2016-05-13

    Immunoglobulin A (IgA) induction primarily occurs in intestinal Peyer's patches (PPs). However, the cellular interactions necessary for IgA class switching are poorly defined. Here we show that in mice, activated B cells use the chemokine receptor CCR6 to access the subepithelial dome (SED) of PPs. There, B cells undergo prolonged interactions with SED dendritic cells (DCs). PP IgA class switching requires innate lymphoid cells, which promote lymphotoxin-β receptor (LTβR)-dependent maintenance of DCs. PP DCs augment IgA production by integrin αvβ8-mediated activation of transforming growth factor-β (TGFβ). In mice where B cells cannot access the SED, IgA responses against oral antigen and gut commensals are impaired. These studies establish the PP SED as a niche supporting DC-B cell interactions needed for TGFβ activation and induction of mucosal IgA responses. PMID:27174992

  17. Acute Cresentric IgA Nephritis in a Patient with Hodgkin's Lymphoma

    OpenAIRE

    Ebru GÖK OĞUZ; Bulut, Mesudiye; Müge EREK; Özkayar, Nihal; Didem TURGUT; Fatih DEDE

    2014-01-01

    In glomerular diseases, the occurence of lymphoma is mostly observed in the form of both minimal change disease and Hodgkin’s lymphoma. The coocurrence of Membranous nephropathy and membranoproliferative glomerulonephritis are generally associated with non-Hodgkin’s lymphoma. While Ig A nephropathy-lymphoma association is rare, it is generally observed in the form of non- Hodgkin’s lymphoma, and there are also cases proposed the cooccurence of Ig A nephropathy and cutaneous T-cell lymphoma. I...

  18. Quantitative estimation of IgA in rats: a comparison of two methods

    International Nuclear Information System (INIS)

    Two methods for estimating IgA in body fluids of rats were devised and tested for their accuracy and reliability. Specifically purified monomeric and polymeric IgA was prepared so that results obtained could be properly assessed. The two systems tried were rocket immunoelectrophoresis, carried out after reduction of samples with dithiothreitol and using monomeric IgA as standard, and a radioimmunoassay utilising a double antibody precipitation method and polymeric IgA as standard. Rocket immunoelectrophoresis was found generally unsuitable for IgA estimation: the reduction methods employed were found to be unreliable or unsuitable for some samples, and the estimation of IgA in bile by this method was further complicated by the presence of IgA fragments. The radio-immunoassay system, however, could be used to estimate IgA to a lower limit of 1 μg/ml, and accurate results could be obtained almost irrespective of the molecular weights of the IgA in the sample. (Auth.)

  19. Mutagenesis of the human IgA1 heavy chain tailpiece that prevents dimer assembly.

    Science.gov (United States)

    Atkin, J D; Pleass, R J; Owens, R J; Woof, J M

    1996-07-01

    The structural features of the human IgA1 tailpiece required for interaction with J chain in IgA dimer assembly were investigated using a protein engineering approach. Wild-type and mutant forms of IgA1 were expressed in the mouse myeloma cell line, J558L, which endogenously expresses J chain. Wild-type IgA1 was secreted as a mixture of dimers and monomers. Deletion of the entire tailpiece by stop codon introduction completely prevented dimer formation. Similarly, substitution of the penultimate residue of the tailpiece, Cys471, with serine resulted in the secretion of IgA monomers alone. Substitution of Asn459 with alanine to prevent attachment of N-linked carbohydrate to the tailpiece also resulted in markedly reduced dimer assembly. These results indicate the critical role played by the tailpiece, and Cys471 in particular, in IgA dimerization. In addition, we found tailpiece-deleted IgA1 and the Cys to Ser471 mutant IgA1 were secreted as mixtures of covalently associated monomers (alpha 2L2) and alpha L half-molecules. The tailpiece may thus play some role in promoting the association of alpha-chains required for IgA monomer assembly. PMID:8683109

  20. Childhood Obesity

    OpenAIRE

    Aydın, Ahmet; Koca, Fahrettin; Fıçıcıoğlu, Can; Çam, Halit; Mıkla, Şerare

    1995-01-01

    Management of childhood obesity and its early and late complications are among the most difficult problems confronted by pediatricians and practitioners The purpose of this review is to provide information for the evaluation and treatment of childhood obesity Key nbsp;words: nbsp;Child Obesity Etiology Management Complications

  1. Dermatose por IgA linear induzida pela gestação Linear IgA dermatosis induced by pregnancy

    Directory of Open Access Journals (Sweden)

    Telma Kanagusuko

    2008-02-01

    Full Text Available A dermatose por IgA linear é doença bolhosa auto-imune subepidérmica rara, caracterizada pelo depósito linear de IgA na zona da membrana basal da epiderme. Nos relatos de gestação em pacientes com essa dermatose, nota-se sempre melhora do quadro clínico. Contrariando essas observações,é apresentado caso de dermatose por IgA linear induzida pela gestação, que demonstrou boa resposta terapêutica à dapsona e prednisona , sem complicações materno-fetais.Linear IgA disease is a rare autoimmune subepidermal bullous disorder characterized by linear IgA deposits at the epidermal basement membrane zone. According to the literature, in patients who have linear IgA disease and become pregnant, the disease tends to improve. We report a case of linear IgA disease induced by pregnancy, successfully treated with dapsone and prednisone with no adverse effects observed in the patient and her newborns.

  2. IgA in the horse: cloning of equine polymeric Ig receptor and J chain and characterization of recombinant forms of equine IgA.

    Science.gov (United States)

    Lewis, M J; Wagner, B; Irvine, R M; Woof, J M

    2010-11-01

    As in other mammals, immunoglobulin A (IgA) in the horse has a key role in immune defense. To better dissect equine IgA function, we isolated complementary DNA (cDNA) clones for equine J chain and polymeric Ig receptor (pIgR). When coexpressed with equine IgA, equine J chain promoted efficient IgA polymerization. A truncated version of equine pIgR, equivalent to secretory component, bound with nanomolar affinity to recombinant equine and human dimeric IgA but not with monomeric IgA from either species. Searches of the equine genome localized equine J chain and pIgR to chromosomes 3 and 5, respectively, with J chain and pIgR coding sequence distributed across 4 and 11 exons, respectively. Comparisons of transcriptional regulatory sequences suggest that horse and human pIgR expression is controlled through common regulatory mechanisms that are less conserved in rodents. These studies pave the way for full dissection of equine IgA function and open up possibilities for immune-based treatment of equine diseases. PMID:20631692

  3. Effect of mutations in the human immunoglobulin A1 (IgA1) hinge on its susceptibility to cleavage by diverse bacterial IgA1 proteases.

    Science.gov (United States)

    Senior, Bernard W; Woof, Jenny M

    2005-03-01

    Components of the human immunoglobulin A1 (IgA1) hinge governing sensitivity to cleavage by bacterial IgA1 proteases were investigated. Recombinant antibodies with distinct hinge mutations were constructed from a hybrid comprised of human IgA2 bearing half of the human IgA1 hinge region. This hybrid antibody and all the mutant antibodies derived from it were resistant to cleavage by the IgA1 proteases from Streptococcus oralis and Streptococcus mitis biovar 1 strains but were cleaved to various degrees by those of Streptococcus pneumoniae, some Streptococcus sanguis strains, and the type 1 and 2 IgA1 proteases of Haemophilus influenzae, Neisseria meningitidis, and Neisseria gonorrhoeae. Remarkably, those proteases that cleave a Pro-Ser peptide bond in the wild-type IgA1 hinge were able to cleave mutant antibodies lacking a Pro-Ser peptide bond in the hinge, and those that cleave a Pro-Thr peptide bond in the wild-type IgA1 hinge were able to cleave mutant antibodies devoid of a Pro-Thr peptide bond in the hinge. Thus, the enzymes can cleave alternatives to their preferred postproline peptide bond when such a bond is unavailable. Peptide sequence analysis of a representative antibody digestion product confirmed this conclusion. The presence of a cleavable peptide bond near the CH2 end of the hinge appeared to result in greater cleavage than if the scissile bond was at the CH1 end of the hinge. Proline-to-serine substitution at residue 230 in a hinge containing potentially cleavable Pro-Ser and Pro-Thr peptide bonds increased the resistance of the antibody to cleavage by many IgA1 proteases. PMID:15731049

  4. Therapeutic potential of Keishi-bukuryo-gan on diabetic nephropathy

    OpenAIRE

    中川, 孝子

    2004-01-01

    Keishi-bukuryo-gan is a Chinese traditional medicine, which is used clinically as a vascular system disordereliminating drug. This review summarizes the effects of Keishi-bukuryo-gan on the occurrence and progression of diabetic nephropathy. To prove its usefulness, we employed two kinds of experimental model animals ; diabetic nephropathy rats induced by subtotal nephrectomy plus streptozotocin injection and spontaneously diabetic WBN/Kob rats. In both animal models, Keishi-bukuryo-gan treat...

  5. Erythropoietin Produktion bei akuter und chronischer obstruktiven Nephropathie

    OpenAIRE

    Tawosh, Ammar

    2008-01-01

    EPO is a circulating hormon that stimulates erythrocyte generation in bone marrow. EPO is secreted by the kidney and its production is stimulated following hypoxic stimuli. Little is known about the influence of obtructive nephropathy on hypoxia-stimulated EPO production. Therefore, we established a model of obstructive nephropathy (ONP) by unilateral ureteral ligation (UUL) in rats which were subjected to CO and hypobaric hypoxia (8% O2). We also tested the reversibility of UUL on EPO plasma...

  6. Preventive effect of taurine on experimental type II diabetic nephropathy

    OpenAIRE

    Lin Shumei; Yang Jiancheng; Wu Gaofeng; Liu Mei; Luan Xinhong; Lv Qiufeng; Zhao He; Hu Jianmin

    2010-01-01

    Abstract Background It has been verified that taurine has some preventive effects on diabetes and its complications when used alone or together with other drugs, but there are few reports about taurine on the prevention of diabetic nephropathy, the mechanisms of which are still unknown. Methods Taurine was administered to type Ⅱ diabetic rats induced by high fat high sugar diet combined with STZ injection. The preventive effect of taurine on diabetic nephropathy was investigated by detecting ...

  7. Vesicoureteral Reflux, Reflux Nephropathy, and End-Stage Renal Disease

    OpenAIRE

    Paul Brakeman

    2008-01-01

    Objective. To review the contribution of vesicoureteral reflux and reflux nephropathy to end-stage renal disease. Data Source. Published research articles and publicly available registries. Results. Vesicoureteral reflux (VUR) is commonly identified in pediatric patients and can be associated with reflux nephropathy (RN), chronic kidney disease (CKD), and rarely end-stage renal disease (ESRD). Patients with reduced GFR, bilateral disease, grade V VUR, proteinuria, and hypertension are more l...

  8. Contrast medium-induced nephropathy: the pathophysiology

    DEFF Research Database (Denmark)

    Persson, P B; Tepel, Martin

    2006-01-01

    A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN...... haemodynamics, regional hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen species) to direct cytotoxic effects. Although these potential mediators of CIN will be discussed separately, several factors may act in concert to perturb kidney function after exposure to contrast media. From...... the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting...

  9. Acute bile nephropathy secondary to anabolic steroids.

    Science.gov (United States)

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

  10. Complex networks analysis of obstructive nephropathy data

    Science.gov (United States)

    Zanin, M.; Boccaletti, S.

    2011-09-01

    Congenital obstructive nephropathy (ON) is one of the most frequent and complex diseases affecting children, characterized by an abnormal flux of the urine, due to a partial or complete obstruction of the urinary tract; as a consequence, urine may accumulate in the kidney and disturb the normal operation of the organ. Despite important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks, based on vectors of features of control and ON subjects, is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction.

  11. Role of metabolic control on diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Macedo Célia Sperandéo

    2002-01-01

    Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

  12. Diabetic nephropathy in Africa: A systematic review

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To determine the prevalence and incidence ofdiabetic nephropathy in Africa.METHODS: We performed a systematic narrativereview of published literature following the MOOSEGuidelines for Meta-Analysis and Systematic Reviewsof Observational Studies. We searched PubMed-MEDLINE for all articles published in English and Frenchlanguages between January 1994 and July 2014 usinga predefined strategy based on the combination ofrelevant terms and the names of each of the 54 Africancountries and African sub-regions to capture the largestnumber of studies, and hand-searched the referencelists of retrieved articles. Included studies reported onthe prevalence, incidence or determinants of chronickidney disease (CKD) in people with diabetes withinAfrican countries.RESULTS: Overall, we included 32 studies from 16countries; two being population-based studies andthe remaining being clinic-based surveys. Most of thestudies (90.6%) were conducted in urban settings.Methods for assessing and classifying CKD variedwidely. Measurement of urine protein was the mostcommon method of assessing kidney damage (62.5%of studies). The overall prevalence of CKD varied from11% to 83.7%. Incident event rates were 94.9% forproteinuria at 10 years of follow-up, 34.7% for endstagerenal disease at 5 years of follow-up and 18.4%for mortality from nephropathy at 20 years of followup.Duration of diabetes, blood pressure, advancingage, obesity and glucose control were the commondeterminants of kidney disease.CONCLUSION: The burden of CKD is importantamong people with diabetes in Africa. High quality datafrom large population-based studies with validatedmeasures of kidney function are still needed to bettercapture the magnitude and characteristics of diabeticnephropathy in Africa.

  13. Contrast-induced nephropathy in interventional cardiology

    Directory of Open Access Journals (Sweden)

    Sudarsky D

    2011-07-01

    Full Text Available Doron Sudarsky, Eugenia NikolskyCardiology Department, Rambam Health Care Campus and Technion-Israel Institute of Technology, Haifa, IsraelAbstract: Development of contrast-induced nephropathy (CIN, ie, a rise in serum creatinine by either ≥0.5 mg/dL or by ≥25% from baseline within the first 2–3 days after contrast administration, is strongly associated with both increased inhospital and late morbidity and mortality after invasive cardiac procedures. The prevention of CIN is critical if long-term outcomes are to be optimized after percutaneous coronary intervention. The prevalence of CIN in patients receiving contrast varies markedly (from <1% to 50%, depending on the presence of well characterized risk factors, the most important of which are baseline chronic renal insufficiency and diabetes mellitus. Other risk factors include advanced age, anemia, left ventricular dysfunction, dehydration, hypotension, renal transplant, low serum albumin, concomitant use of nephrotoxins, and the volume of contrast agent. The pathophysiology of CIN is likely to be multifactorial, including direct cytotoxicity, apoptosis, disturbances in intrarenal hemodynamics, and immune mechanisms. Few strategies have been shown to be effective to prevent CIN beyond hydration, the goal of which is to establish brisk diuresis prior to contrast administration, and to avoid hypotension. New strategies of controlled hydration and diuresis are promising. Studies are mixed on whether prophylactic oral N-acetylcysteine reduces the incidence of CIN, although its use is generally recommended, given its low cost and favorable side effect profile. Agents which have been shown to be ineffective or harmful, or for which data supporting routine use do not exist, include fenoldopam, theophylline, dopamine, calcium channel blockers, prostaglandin E1, atrial natriuretic peptide, statins, and angiotensin-converting enzyme inhibitors.Keywords: contrast-induced nephropathy, contrast media

  14. Evaluation of the Diagnostic Accuracy of a New Dengue IgA Capture Assay (Platelia Dengue IgA Capture, Bio-Rad) for Dengue Infection Detection

    OpenAIRE

    Sophie De Decker; Muriel Vray; Viridiana Sistek; Bhety Labeau; Antoine Enfissi; Dominique Rousset; Séverine Matheus

    2015-01-01

    Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, I...

  15. CCL28 Controls Immunoglobulin (Ig)A Plasma Cell Accumulation in the Lactating Mammary Gland and IgA Antibody Transfer to the Neonate

    OpenAIRE

    Wilson, Eric; Butcher, Eugene C.

    2004-01-01

    The accumulation of immunoglobulin (Ig)A antibody-secreting cells (ASCs) in the lactating mammary gland leads to secretion of antibodies into milk and their passive transfer to the suckling newborn. This transfer of IgA from mother to infant provides transient immune protection against a variety of gastrointestinal pathogens. Here we show that the mucosal epithelial chemokine CCL28 is up-regulated in the mammary gland during lactation and that IgA ASCs from this tissue express CCR10 and migra...

  16. "Iga päev..." : [luuletused] / Doris Kareva

    Index Scriptorium Estoniae

    Kareva, Doris, 1958-

    2001-01-01

    Tekst eesti ja inglise k. D. Kareva lühibiograafia eesti ja inglise k. lk. 175. Sisu: "Iga päev..." = "Every day..." ; "Ma nägin unes - Saatan kõneles..." = "I dream that I heard Satan speak..." ; "Viib sünnieelsest unest surmaunne..." = "Rainbow-coloured confusion bears us..." ; "Vaadeldes vikerkaarlevat maailma..." = "Viewing the rainbowing world..." ; "Ei jõua kirjutada puhtandit..." = "No time to write the final draft..." ; "Põletatud luuletused..." = ""Burnt poems..." ; Fraktalia ; Müsteerium 1-5 = Enigma 1-5 ; "Jumal juhtub..." = "God happens..." ; Moira 1-7 = Wishing well 1-7 ; Concerto strumenti e voce

  17. An unusual presentation of childhood vasculitis presenting in adulthood: A challenging diagnosis of Henoch-Schönlein Purpura

    Directory of Open Access Journals (Sweden)

    Charat Thongprayoon

    2014-01-01

    Full Text Available Context: Henoch-Schφnlein purpura (HSP, a systemic IgA vascultitis, is uncommon in adults, with an incidence rate of 0.1 to 1.2 per million in adults over 20 years old. This vasculitic syndrome can present as an uncommon cause of intestinal obstruction in older patients. We report a case of an older woman with HSP presenting with small bowel obstruction and vasculitic rash. Case Report: We report a 67-year-old woman who presented with small bowel obstruction and skin rash. Skin biopsy revealed leukocytoclastic vasculitis with +IgA granular deposition within the walls of superficial dermal vessels. Kidney biopsy confirmed the diagnosis of HSP with mild mesangial proliferative IgA nephropathy. Her abdominal pain and small bowel obstruction were improved with conservative treatment. She continued to do well with normal kidney function at a 3-month follow-up visit. Conclusion: HSP, a systemic IgA vasculitis, is a predominantly pediatric vasculitis and is uncommon in adults. In adults, the disease process is identical to that in children. However, gastrointestinal manifestation is less common in older patients, and bowel perforation and obstruction are rare. Intestinal obstruction with skin rash and renal involvement should raise suspicions of HSP.

  18. Selective IgA deficiency associated with allergy to cow's milk protein, case report

    OpenAIRE

    Cristina Isabel Herrera Morales

    2015-01-01

    Background: IgA is the most abundant immunoglobulin in the human; it is found in tissues and in secretions especially from the gastrointestinal tract reflecting its role in mucosal immunity and the development of tolerance. Selective IgA deficiency (

  19. Childhood Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  20. Childhood leukaemia

    International Nuclear Information System (INIS)

    The debate on whether there is any link between leukaemia clusters and nuclear installations has been raging since the early eighties. A Government Inquiry found no link between childhood leukaemia and residence near Seascale, an area near British Nuclear Fuels Sellafield plant. Research in the 1980s linked childhood leukaemia to fathers' occupations prior to conception in the Seascale plant but also to workers in the iron, steel, farming and chemical industries. This article reviews research findings to date. (UK)

  1. Renal Biopsy in Patients Developing Severe Pre-eclampsia: Crescentic IgA Nephritis

    Directory of Open Access Journals (Sweden)

    Dilek GİBYELİ GENEK

    2011-09-01

    Full Text Available IgA nephritis is known as the most common glomerulonephritis and a disease with good prognosis. Acute renal failure, nephrotic syndrome and malignant hypertension can be seen less than 10% of patients with IgA nephritis. Acute renal failure occurs due to crescentic IgA nephritis or tubular occlusion or tubuler injury due to severe glomerular hematuria. IgA nephritis in pregnancy have a good prognosis. On the other hand; the most common renal complication during pregnancy is development of preeclampsia. Preeclampsia occurs in approximately 5% of all pregnancies. Underlying renal pathology increases the risk of preeclampsia. We presented this case with cresentic IgA nephritis with severe preeclampsia to emphasize this issue.

  2. Study of the IGA/SCC behavior of Alloy 600 and 690 in high temperature solutions

    International Nuclear Information System (INIS)

    IGA/SCC of Alloy 600 steam generator (SG) tubes in the secondary side has been recognized as a matter of great concern for PWRs. IGA/SCC behavior of Alloy 600 and 690 in high temperature solutions were studied using CERT method under potentiostatic conditions. The IGA/SCC susceptible regions were investigated as the function of pH and electrode potential. To understand the cause of IGA/SCC, the electrochemical measurements and surface film analysis were also performed in acidic and alkaline solutions. To verify the results of CERT test, the long term model boiler tests were also carried out. Thermally treated Alloy 690 showed higher IGA/SCC resistance than Alloy 600 under both acid and alkaline conditions

  3. PetIGA: A framework for high-performance isogeometric analysis

    KAUST Repository

    Dalcin, L.

    2016-05-25

    We present PetIGA, a code framework to approximate the solution of partial differential equations using isogeometric analysis. PetIGA can be used to assemble matrices and vectors which come from a Galerkin weak form, discretized with Non-Uniform Rational B-spline basis functions. We base our framework on PETSc, a high-performance library for the scalable solution of partial differential equations, which simplifies the development of large-scale scientific codes, provides a rich environment for prototyping, and separates parallelism from algorithm choice. We describe the implementation of PetIGA, and exemplify its use by solving a model nonlinear problem. To illustrate the robustness and flexibility of PetIGA, we solve some challenging nonlinear partial differential equations that include problems in both solid and fluid mechanics. We show strong scaling results on up to 40964096 cores, which confirm the suitability of PetIGA for large scale simulations.

  4. Bench-to-bedside review: preventive measures for contrast-induced nephropathy in critically ill patients

    OpenAIRE

    Berk, van den, G.E.; Tonino, S.; Fijter, de, C.; Smit, W.; Schultz, M.J

    2005-01-01

    An increasing number of diagnostic imaging procedures requires the use of intravenous radiographic contrast agents, which has led to a parallel increase in the incidence of contrast-induced nephropathy. Risk factors for development of contrast-induced nephropathy include pre-existing renal dysfunction (especially diabetic nephropathy and multiple myeloma-associated nephropathy), dehydration, congestive heart failure and use of concurrent nephrotoxic medication (including aminoglycosides and a...

  5. Solution structure determination of monomeric human IgA2 by X-ray and neutron scattering, analytical ultracentrifugation and constrained modelling: a comparison with monomeric human IgA1.

    Science.gov (United States)

    Furtado, Patricia B; Whitty, Patrick W; Robertson, Alexis; Eaton, Julian T; Almogren, Adel; Kerr, Michael A; Woof, Jenny M; Perkins, Stephen J

    2004-05-14

    Immunoglobulin A (IgA), the most abundant human immunoglobulin, mediates immune protection at mucosal surfaces as well as in plasma. It exists as two subclasses IgA1 and IgA2, and IgA2 is found in at least two allotypic forms, IgA2m(1) or IgA2m(2). Compared to IgA1, IgA2 has a much shorter hinge region, which joins the two Fab and one Fc fragments. In order to assess its solution structure, monomeric recombinant IgA2m(1) was studied by X-ray and neutron scattering. Its Guinier X-ray radius of gyration R(G) is 5.18 nm and its neutron R(G) is 5.03 nm, both of which are significantly smaller than those for monomeric IgA1 at 6.1-6.2 nm. The distance distribution function P(r)for IgA2m(1) showed a broad peak with a subpeak and gave a maximum dimension of 17 nm, in contrast to the P(r) curve for IgA1, which showed two distinct peaks and a maximum dimension of 21 nm. The sedimentation coefficients of IgA1 and IgA2m(1) were 6.2S and 6.4S, respectively. These data show that the solution structure of IgA2m(1) is significantly more compact than IgA1. The complete monomeric IgA2m(1) structure was modelled using molecular dynamics to generate random IgA2 hinge structures, to which homology models for the Fab and Fc fragments were connected to generate 10,000 full models. A total of 104 compact best-fit IgA2m(1) models gave good curve fits. These best-fit models were modified by linking the two Fab light chains with a disulphide bridge that is found in IgA2m(1), and subjecting these to energy refinement to optimise this linkage. The averaged solution structure of the arrangement of the Fab and Fc fragments in IgA2m(1) was found to be predominantly T-shaped and flexible, but also included Y-shaped structures. The IgA2 models show full steric access to the two FcalphaRI-binding sites at the Calpha2-Calpha3 interdomain region in the Fc fragment. Since previous scattering modelling had shown that IgA1 also possessed a flexible T-shaped solution structure, such a T-shape may be

  6. Determination of levels of salivary IgA subclasses in patients with minor recurrent aphthous ulcer

    Directory of Open Access Journals (Sweden)

    Ramandeep Saluja

    2012-01-01

    Full Text Available Context: Recurrent Aphthous Ulcer (RAU is an inflammatory disease characterized by recurrent, painful oral ulcers. It is of multifactorial etiology. Salivary immunoglobulins have important role in the protection of mucosal surfaces. Aim: The aim of this study was to determine salivary immunoglobulin A1 (IgA1 and IgA2 in acute and remission phases of the disease. Materials and Methods: Thirty clinically confirmed cases of RAU and 30 age-and sex-matched controls were included in the study. After detailed case history and thorough clinical examination, 2 mL of saliva was collected in both acute and remission phases of the disease. The obtained saliva samples were subjected to quantification of IgA1 and IgA2 levels using RID kit. Results: The mean IgA2 level was significantly higher (P<.001 in both acute and remission phase of the study group. The mean IgA1 level also showed a significant increase in the acute phase compared to remission as well as controls (P<.05. Females exhibited a higher level in acute phase for IgA1 and in both phases for IgA2 (P<.05. Conclusion: The results associated with clinical observations suggest that acute phase is characterized with increase in IgA2 that might reflect increased immune response as a possible result of the microbial stimulation seen in the acute phase in comparison to the remission period. IgA plays an important role in the pathogenesis of RAU and it can be used as a parameter to assess the mucosal immune status

  7. Vitamin D receptor and its protective role in diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Guan Xiaoling; Yang Huajie; Zhang Wei; Wang Huanjun; Liao Lin

    2014-01-01

    Objective To review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.Study selection Articles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.Results The ligands as well as construction and tissue distribution of vitamin D receptor were summarized.Pathogenesis of diabetic nephropathy was analyzed.The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system,anti-inflammation,anti-fibrosis and the reduction of proteinuria were reviewed.Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.Conclusion Our study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.

  8. Paracetamol and analgesic nephropathy: Are you kidneying me?

    Directory of Open Access Journals (Sweden)

    Waddington F

    2014-12-01

    Full Text Available Freya Waddington, Mark Naunton, Jackson Thomas Faculty of Health, University of Canberra, Canberra, ACT, Australia Introduction: Analgesic nephropathy is a disease resulting from the frequent use of combinations of analgesic medications over many years, leading to significant impairment of renal function. The observation of a large number of cases of renal failure in patients abusing analgesic mixtures containing phenacetin led to the initial recognition of the nephrotoxicity from the use of analgesics. Phenacetin was subsequently exclusively blamed for this disease. However, the role of a single analgesic as a sole cause of analgesic nephropathy was challenged, and a number of researchers have since attempted to determine the extent of involvement of other analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs, aspirin, and paracetamol. Case presentation: We present the case of an 83-year-old woman with a history of NSAID-induced nephropathy with poor pain control and reluctance to use paracetamol. We attempt to briefly review the evidence of paracetamol being implicated in the development of analgesic-induced nephropathy. Conclusion: There is a lack of concrete data regarding causative analgesics, including paracetamol. Patients should therefore not be withheld paracetamol, an effective and commonly recommended agent, for fear of worsening renal function. Keywords: kidney, paracetamol, nephropathy, phenacetin

  9. Chronic hypokalemic nephropathy: a clinical study.

    Science.gov (United States)

    Bock, K D; Cremer, W; Werner, U

    1978-01-01

    Description of 23 patients (21 women, 2 men) with an average age of 36.6 (19--68) years, who were hypokalemic during 6.5 years on the average (range 1/2--16 years). The cause of the potassium depletion was malnutrition (anorexia nervosa, vomiting) and/or abuse of laxatives and/or diuretics. With increasing duration of potassium depletion renal function deteriorated; in two cases terminal renal failure developed. Histology of the kidneys (9 cases) showed the picture of chronic abacterial interstitial nephritis. Urinalysis was negative or non-specific. The blood pressure levels were normal or low, hypertensive values being exceptional. Aside of hypokalemia a tendency to hyponatriemia, hypochloremia and metabolic alcalosis was observed, the latter turning into hypokalemic normochloremic acidosis with advancing renal insufficiency. Plasma renin activity and aldosterone concentration or excretion frequently were elevated, but no close correlation was found between these parameters or with the blood pressure. Bacterial infection of the urinary tract occured, if at all, in the late phase and seems to be complication rather than the cause of the kidney disease. The discussion of other possible pathogenetic factors leads to the conclusion that the term "chronic kaliopenic nephropathy" is justified. Some diagnostic and therapeutic consequences are mentioned. PMID:732256

  10. Balkan nephropathy: evolution of our knowledge.

    Science.gov (United States)

    Bamias, Giorgos; Boletis, John

    2008-09-01

    Balkan endemic nephropathy (BEN), originally described in the late 1950s as a chronic tubulointerstitial kidney disease, is identified by its unique epidemiological features. The most remarkable characteristic of BEN is the focal topographical nature that characterizes its occurrence at the global, national, and even household level. BEN affects only certain endemic rural foci along tributaries of the Danube River in the Balkan countries of Bosnia, Bulgaria, Croatia, Romania, and Serbia. The spatial distribution has remained astonishingly unchanged with time because the disease affects the same endemic clusters as 50 years ago. The natural course of the disease is characterized by universal development of end-stage renal disease and the frequent development of upper urinary tract tumors, posing a substantial disease burden to the afflicted areas. The greatest challenge in the study of BEN has been the elucidation of its cause. The unique features of the disease, in particular its endemic nature and the long incubation period required for the disease to develop, have led to the proposal that BEN represents a unique environmental disease. The quest for the responsible environmental factor has been long and diverse, and although no definitive answer has been provided to date, converging lines of evidence support the theory that long-term consumption of food contaminated with aristolochic acid underlies the pathogenesis of BEN. The present review describes the evolution of our knowledge of BEN in relation to the development of the main theories for its pathogenesis. PMID:18725017

  11. Histone Lysine Methylation in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Guang-dong Sun

    2014-01-01

    Full Text Available Diabetic nephropathy (DN belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

  12. Improved prognosis of diabetic nephropathy in type 1 diabetes

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken L; Carstensen, Bendix;

    2015-01-01

    The natural history of diabetic nephropathy offered an average survival of only 5-7 years. During the past decades, multiple changes in therapy and lifestyle have occurred. The prognosis of diabetic nephropathy after implementing stricter control of blood pressure (including increased use of long......-term renin-angiotensin system inhibition), lipids, and glycemia, along with less smoking and other lifestyle and treatment advancements, is inadequately analyzed. To clarify this, we studied 497 patients with type 1 diabetes and diabetic nephropathy at the Steno Diabetes Center and compared them...... previously 4.0 to 3.3 ml/min per 1.73 m2/year. During a median follow-up of 9.1 years, 29% of participants doubled their plasma creatinine or developed end-stage renal disease. Mortality risk was similar to our prior study (hazard ratio 1.05 (0.76-1.43). However, after age adjustment, as both diabetes...

  13. Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

    International Nuclear Information System (INIS)

    Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter.

  14. Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

    2012-01-15

    Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter.

  15. Significance of serum IgA in patients with acute hepatitis E virus infection

    Institute of Scientific and Technical Information of China (English)

    De-Ying Tian; Yan Chen; Ning-Shao Xia

    2006-01-01

    AIM: To study the significance of serum anti-hepatitis E virus (HEV) IgA in patients with hepatitis E.METHODS: A new method was established to assay anti-HEV IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA.RESULTS: The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20 ± 11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90 ± 15 d and 120 ± 23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA (P <0.05).CONCLUSION: The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.

  16. Childhood obesity

    DEFF Research Database (Denmark)

    Heitmann, Berit L; Koplan, Jeffrey; Lissner, Lauren

    2009-01-01

    Despite progress toward assuring the health of today's young population, the 21(st) century began with an epidemic of childhood obesity. There is general agreement that the situation must be addressed by means of primary prevention, but relatively little is known about how to intervene effectively....... The evidence behind the assumption that childhood obesity can be prevented was discussed critically in this roundtable symposium. Overall, there was general agreement that action is needed and that the worldwide epidemic itself is sufficient evidence for action. As the poet, writer, and scholar...

  17. Autoimmunity in Membranous Nephropathy Targets Aldose Reductase and SOD2

    OpenAIRE

    Prunotto, Marco; Carnevali, Maria Luisa; Candiano, Giovanni; Murtas, Corrado; Bruschi, Maurizio; Corradini, Emilia; Trivelli, Antonella; Magnasco, Alberto; Petretto, Andrea; Santucci, Laura; Mattei, Silvia; Gatti, Rita; Scolari, Francesco; Kador, Peter; Allegri, Landino

    2010-01-01

    Glomerular targets of autoimmunity in human membranous nephropathy are poorly understood. Here, we used a combined proteomic approach to identify specific antibodies against podocyte proteins in both serum and glomeruli of patients with membranous nephropathy (MN). We detected specific anti–aldose reductase (AR) and anti–manganese superoxide dismutase (SOD2) IgG4 in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG4 from microdissected glomeruli of three biopsi...

  18. Specific Blood Pressure Targets for Patients With Diabetic Nephropathy?

    Science.gov (United States)

    Grassi, Guido; Mancia, Giuseppe; Nilsson, Peter M

    2016-08-01

    Diabetic nephropathy represents a condition frequently detected in current clinical practice characterized by a very high cardiovascular risk profile. Blood pressure reduction via antihypertension drug treatment represents a therapeutic approach capable of exerting favorable effects on renal and cardiovascular outcomes. The purpose of this article is to review the current literature and results of key clinical trials pertaining to blood pressure goals of antihypertension treatment in these patients. The pros and cons of a less or a more intensive blood pressure goal in diabetic nephropathy will be discussed, with particular emphasis on the cardiovascular and renal effects of each therapeutic strategy. PMID:27440837

  19. Secretory IgA as a diagnostic tool for Pseudomonas aeruginosa respiratory colonization

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Johansen, Helle Krogh; Poulsen, Steen Seier; Pressler, Tacjana; Buchwald, Christian; Høiby, Niels

    2012-01-01

    BACKGROUND: Pseudomonas aeruginosa sinusitis may be the focus for intermittent lung colonization in patients with cystic fibrosis (CF). The sinusitis may induce elevated IgA levels in nasal secretion and saliva against P. aeruginosa. METHODS: 120 CF patients chronically infected, intermittently...... colonized or without P. aeruginosa in the lungs participated in this cross-sectional study. IgA and IgG against P. aeruginosa sonicate and alginate were measured in nasal secretions, saliva, and in serum by ELISA. RESULTS: The intermittently colonized patients had significantly higher IgA levels in nasal...

  20. Iodinated contrast agent-induced nephropathy

    International Nuclear Information System (INIS)

    Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management. A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.). (orig.)

  1. Detection of rubella-specific serum IgG and IgA and nasopharyngeal IgA responses using a radioactive single radial immunodiffusion technique

    International Nuclear Information System (INIS)

    A radioactive, single radial immunodiffusion technique (RSRID) employing 125I-labelled antiglobulins, was developed to determine rubella-specific serum IgG and IgA and nasopharyngeal IgA antibody responses following both naturally acquired rubella and vaccination with four attenuated vaccines. Rubella-specific IgG antibodies developed in parallel with haemagglutination inhibiting (HAI) antibodies and both persisted for at least a year in all cases of naturally acquired and vaccine induced infection. However, the RSRID test detected rises in titre in all of five volunteers challenged intranasally with RA27/3, whereas only one volunteer showed a rise by HAI. Serum IgA antibodies generally persisted for at least a year following naturally acquired infection but rubella vaccines induced variable responses. Thus, following administration of RA27/3 and To-336 vaccines, rubella-specific IgA usually persisted for a year, whereas Cendehill vaccine failed to induce a detectable response. Rubella-specific nasopharyngeal IgA was detected in all five patients following naturally acquired infection and was still present in the only two patients tested a year after infection. These antibodies were detected in fourteen of twenty-three vaccinees at 3 weeks, but persisted for a year in only two vaccinees, both of whom were given RA27/3 intranasally. (author)

  2. Childhood Obesity

    Science.gov (United States)

    Yuca, Sevil Ari, Ed.

    2012-01-01

    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  3. Childhood Obesity

    Centers for Disease Control (CDC) Podcasts

    2013-08-06

    In this podcast, Dr. Tom Frieden, CDC Director, discusses the decrease in childhood obesity rates and what strategies have been proven to work to help our children grow up and thrive.  Created: 8/6/2013 by National Center for Injury Prevention and Control.   Date Released: 3/6/2014.

  4. Iga seitsmes kindlustusvõtja üritab seltsi petta / Erkki Erilaid

    Index Scriptorium Estoniae

    Erilaid, Erkki

    2003-01-01

    Kindlustusseltside hinnangul üritab iga seitsmes kahjukindlustusvõtja kas kahju suurendada või pärast õnnetust tagantjärele kindlustust vormistades seltse petta. Vt. samas: Näiteid petuskeemidest

  5. Euroliidu odava aseaine tunneb ära iga riik / Urmas Paet

    Index Scriptorium Estoniae

    Paet, Urmas, 1974-

    2007-01-01

    Eesti välisminister Urmas Paet kirjutab Euroopa identiteedist, Euroopa Liidu laienemisest, selle toetamise vajalikkusest ja Türgi ning Balkanimaade perspektiivist EL-iga liitumisel, euroopalike reformide toimumisest neis riikides

  6. Genetic analysis and gene mapping of a mutant dwarf gene IGA-1 in rice

    International Nuclear Information System (INIS)

    The rice material, Hangai-1, which studied in this paper, was a stabile dwarf mutant by space mutation of rice cultivar Texianzhan 13(indica). Genetic analysis showed that its dwarf trait was controlled by two recessive semi-dwarf genes, sd1 and a new semi-dwarf gene, named as iga-1. The new semi-dwarf gene iga-1 was located between microsatellite markers RM6645 and RM3837 on chromosome 5, the genetic distances between them were 0. 07cM and 1.21 cM, respectively. The iga-1 gene is possibly a multiple allele to the d-1 gene. The semi-dwarf mutant with the new semi-dwarf gene iga-1 was found insensitive to gibberellin 3(GA3). (author)

  7. Alteration in serum osteocalcin levels in patients with diabetic nephropathy

    International Nuclear Information System (INIS)

    The fact that bone mass density (BMD) is not useful for assessing fracture risk in diabetic patients (DM) seems problematic, because those populations are increasing in every country. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation. The present study was carried out to evaluate the usefulness of OC as noninvasive biomarker of bone formation in diabetes mellitus type 2 (uncomplicated) and diabetic nephropathy. Immunoradiometric assay(IRMA) was used for the quantitative measurement of human intact OC both N-terminal and C-terminal fragments in the serum of the control and the studied groups. OC levels in the uncomplicated diabetic group were significantly lower while in the diabetic nephropathy group was significantly higher compared to control values . There was a weak negative correlation between OC and both fasting blood glucose and glycated Hb% in the diabetic group. In diabetic nephropathy patients, a weak positive correlation was observed between OC and protein creatinine ratio. The results concluded that changes in bone remodelling marker OC are present in both DM type 2 and diabetic nephropathy explaining osteopenia and osteoporosis observed in both cases.Therefore, an effective glycaemic control should be the hallmark of prevention and treatment of diabetes mellitus induced osteoporosis

  8. Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Smidt, U M;

    1983-01-01

    arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy....

  9. Uric acid as a mediator of diabetic nephropathy

    DEFF Research Database (Denmark)

    Jalal, Diana I; Maahs, David M; Hovind, Peter;

    2011-01-01

    Despite advances in the management of patients with diabetes, diabetic nephropathy (DN) remains the most common cause of end-stage renal disease in the United States and worldwide. Inflammation and endothelial dysfunction appear to play a central role in the onset and the progression of DN. Recent...

  10. Chronic constipation causing obstructive nephropathy in a delayed toddler.

    LENUS (Irish Health Repository)

    Barrett, Michael Joseph

    2012-01-01

    Chronic constipation causing obstructive nephropathy is very rare in children. However, it can cause urinary tract obstruction with acute impairment of renal function with a need for emergent disimpaction. The authors discuss a 2 years 4 months old child who presented to our emergency department with acute renal failure due to faecal impaction.

  11. Diabetic Kidney Disease (Diabetic Nephropathy) (Beyond the Basics)

    Science.gov (United States)

    ... SP, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005; 28:164. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and ... of intensive treatment of type 1 diabetes mellitus on development and ...

  12. Drug induced linear IgA dermatosis: case report and a short review:

    OpenAIRE

    Arzenšek, Jože; Benedičič, Ana; Berčič, Marija; Kansky, Aleksej; Pejovnik Pustinek, Alenka; Vizjak, Alenka; Wojnarowska, Fenella T.

    2003-01-01

    A significant number of reports incriminate various drugs, especially vancomycin and amiodarone of provoking bullous linear IgA dermatosis. This entity also includes the subset of IgA-mediated epidermolysis bullosa acquisita. We report on a patient with histopathologically and immunologicallyproven bullous linear IgA dermatosis, who developed this condition during treatment for hypertension with enalapril. Treatment with lowdoses of dapsone, 25 mg daily, was efficient. There is strong evidenc...

  13. Predicting diabetic nephropathy using a multifactorial genetic model.

    Directory of Open Access Journals (Sweden)

    Ilana Blech

    Full Text Available AIMS: The tendency to develop diabetic nephropathy is, in part, genetically determined, however this genetic risk is largely undefined. In this proof-of-concept study, we tested the hypothesis that combined analysis of multiple genetic variants can improve prediction. METHODS: Based on previous reports, we selected 27 SNPs in 15 genes from metabolic pathways involved in the pathogenesis of diabetic nephropathy and genotyped them in 1274 Ashkenazi or Sephardic Jewish patients with Type 1 or Type 2 diabetes of >10 years duration. A logistic regression model was built using a backward selection algorithm and SNPs nominally associated with nephropathy in our population. The model was validated by using random "training" (75% and "test" (25% subgroups of the original population and by applying the model to an independent dataset of 848 Ashkenazi patients. RESULTS: The logistic model based on 5 SNPs in 5 genes (HSPG2, NOS3, ADIPOR2, AGER, and CCL5 and 5 conventional variables (age, sex, ethnicity, diabetes type and duration, and allowing for all possible two-way interactions, predicted nephropathy in our initial population (C-statistic = 0.672 better than a model based on conventional variables only (C = 0.569. In the independent replication dataset, although the C-statistic of the genetic model decreased (0.576, it remained highly associated with diabetic nephropathy (χ(2 = 17.79, p<0.0001. In the replication dataset, the model based on conventional variables only was not associated with nephropathy (χ(2 = 3.2673, p = 0.07. CONCLUSION: In this proof-of-concept study, we developed and validated a genetic model in the Ashkenazi/Sephardic population predicting nephropathy more effectively than a similarly constructed non-genetic model. Further testing is required to determine if this modeling approach, using an optimally selected panel of genetic markers, can provide clinically useful prediction and if generic models can be

  14. Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid.

    Science.gov (United States)

    Cozzani, Emanuele; Drosera, Massimo; Parodi, Aurora; Carrozzo, Marco; Gandolfo, Sergio; Rebora, Alfredo

    2004-01-01

    Circulating and bound IgA antibodies can be found in the autoimmune blistering diseases, but their prevalence, clinical relevance and target antigens remain unknown. Thirty-two patients with pemphigus, 73 with bullous pemphigoid and 28 with mucous membrane pemphigoid were studied retrospectively. Direct immunofluorescence (DIF) analysis of IgG, IgA, IgM and C3 was carried out for all cases. Sera were studied by standard indirect immunofluorescence, indirect immunofluorescence on salt-split skin, immunoblotting for bullous pemphigoid and mucous membrane pemphigoid and ELISA for pemphigus. With DIF, we found IgA autoantibodies in 22 of all 133 cases. Circulating IgA antibodies to skin were detected in 2 of 3 IgA-DIF-positive patients with pemphigus, in 3 of 6 with bullous pemphigoid, and in 6 of 13 with mucous membrane pemphigoid. We confirm that the IgA reactivity is more frequently associated with mucous membrane involvement, especially in cases without critical involvement (5/8). The role of IgA and its antigenic specificity in these diseases remain unclear. PMID:15370705

  15. In vivo activation of complement by IgA in a rat model.

    Science.gov (United States)

    Stad, R K; Bogers, W M; Thoomes-van der Sluys, M E; Van Es, L A; Daha, M R

    1992-01-01

    In this study we investigated the capacity of rat IgA to activate complement (C) in vivo in a rat model. Rat monomeric (m-), dimeric (d-) and polymeric (p-) IgA MoAbs were injected intravenously and assessed for deposition of C3 and C4 on IgA. By ELISA it was shown that both d- and p-IgA bound C3 whereas no binding of C3 by m-IgA was observed. Polymeric IgA was more efficient in binding of C3 as compared with d-IgA. However, in haemolytic assays no consistent decrease of plasma complement levels was observed except for dimeric IgA which induced a marginal consumption of AP50. When rats were pre-treated with cobra venom factor (CVF) to deplete C3, no C3 deposition was found on m-, d- or p-IgA. Neither m- nor d- or p-IgA was able to bind C4 in vivo. In agreement with the results described above, large sized polymeric IgA was shown to be taken up by Kupffer cells (KC) together with C3. No C3 was detected when rats were depleted of C using CVF. Taken together, the experimental data suggest that d- and p-IgA are able to activate C via the alternative pathway in vivo. PMID:1733628

  16. Isolated lymphoid follicles are not IgA inductive sites for recombinant Salmonella

    International Nuclear Information System (INIS)

    In this study, we investigated whether isolated lymphoid follicles (ILF) play a role in the regulation of intestinal IgA antibody (Ab) responses. The transfer of wild type (WT) bone marrow (BM) to lymphotoxin-α-deficient (LTα-/-) mice resulted in the formation of mature ILF containing T cells, B cells, and FDC clusters in the absence of mesenteric lymph nodes and Peyer's patches. Although the ILF restored total IgA Abs in the intestine, antigen (Ag)-specific IgA responses were not induced after oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin. Moreover, Ag-specific cell proliferation was not detected in the ILF. Interestingly, no IgA anti-LPS Abs were detected in the fecal extracts of LTα-/- mice reconstituted with WT BM. On the basis of these findings, ILF can be presumed to play a role in the production of IgA Abs, but lymphoid nodules are not inductive sites for the regulation of Ag-specific intestinal IgA responses to recombinant Salmonella

  17. Childhood vitiligo

    Directory of Open Access Journals (Sweden)

    Aparna Palit

    2012-01-01

    Full Text Available Childhood vitiligo is often encountered in dermatological practice. When present in infancy or early childhood, various nevoid and hereditary disorders are to be differentiated. In many cases, familial aggregation of the disease is seen and other autoimmune disorders may be associated. Segmental presentation is more common, and limited body surface area involvement is usual in this age group. Children with vitiligo often suffer from anxiety and depression because of their unusual appearance. Management of vitiligo in children is difficult as therapeutic options are restricted when compared to that in adult patients. Selection of treatment should be careful in these patients with the aim to achieve best results with minimal side effects as well as relieving patients′ and parents′ anxiety.

  18. Childhood psoriasis

    OpenAIRE

    Dogra Sunil; Kaur Inderjeet

    2010-01-01

    Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexu...

  19. Childhood Traumatic Grief

    Science.gov (United States)

    ... Educators Resources for Kids and Teens Childhood Traumatic Grief What is Childhood Traumatic Grief? Children grieve in their own way following the ... child may have a condition called Childhood Traumatic Grief (CTG). Thinking about the person who died—even ...

  20. Childhood Cancer Statistics

    Science.gov (United States)

    ... Shop With CureSearch Blog Donate Now Select Page Childhood Cancer Statistics Home > Understanding Children’s Cancer > Childhood Cancer Statistics Childhood Cancer Statistics – Graphs and Infographics Number of Diagnoses ...

  1. Childhood sarcoidosis: Louisiana experience.

    Science.gov (United States)

    Gedalia, Abraham; Khan, Tahir A; Shetty, Avinash K; Dimitriades, Victoria R; Espinoza, Luis R

    2016-07-01

    A retrospective chart review was conducted to detect patients with sarcoidosis seen by pediatric rheumatology service from the period of 1992 to 2013 at Children's hospital of New Orleans. Twenty-seven patients were identified. The average duration of symptoms before diagnosis was 5 (range 1-120) months. Five patients had onset before the age of 5 years and were diagnosed with early-onset sarcoidosis. The most common manifestations at presentation were constitutional symptoms (62 %) followed by ocular (38 %). During the course of illness, 19/27 (70 %) had multiorgan involvement. Common manifestations included uveitis/iritis (77 %), fever (50 %), hilar adenopathy (42 %), arthritis (31 %), peripheral lympadenopathy (31 %), hepatosplenomegaly (31 %), parenchymal lung disease (27 %), and skin rash (19 %). Unusual manifestations included granulomatous bone marrow disease (3 cases), hypertension (2), abdominal aortic aneurysm (large vessel vasculitis; 1), granulomatous hepatitis (1), nephrocalcinosis (1), membranous nephropathy (1), refractory granulomatous interstitial nephritis with recurrence in transplanted kidney (1), CNS involvement (2), parotid gland enlargement (1), and sensorineural hearing loss (1). Biopsy specimen was obtained in 21/27 (77 %) patients, and demonstration of noncaseating granuloma associated with negative stains for mycobacteria and fungi was seen in 18 patients. Elevated angiotensin-converting enzyme level was seen in 74 % of patients. Treatment with oral prednisone was initiated in symptomatic patients with significant clinical improvement. Low-dose methotrexate (MTX) 10-15 mg/m(2)/week orally, as steroid-sparing agent, was administered in 14 patients. Other immunomodulators included cyclophosphamide (2 patients), etanercept (2), infliximab (2), mycophenolate mofetil (1), and tacrolimus (1). Childhood sarcoidosis is prevalent in Louisiana. Most of the affected children present with a multisystem disease associated with

  2. Relationship between serum IV-C, β2-m levels and diabetic nephropathy

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between the serum type IV collagen (IV-C), β2-micro globulin (β2-m) levels and diabetic nephropathy. Methods: Serum IV-C, β2-m levels were measured with RIA in 30 controls and 86 patients with type 2 diabetics mellitus (35 with diabetic nephropathy and 51 without nephropathy). Results: the serum levels of IV-C and β2-m in diabetic patients with nephropathy were significantly higher than those in controls (P0.05). Conclusion: Serum IV-C and β2-m levels increased gradually as the diabetic nephropathy got more severe. They could be a sensitive marker for early diagnosis of development of diabetic nephropathy. (authors)

  3. Relationship between serum leptin and adiponectin levels in patients with primary hypertensive nephropathy

    International Nuclear Information System (INIS)

    Objective: To explore the relationship between serum leptin and adiponectin levels in patients with primary hypertensive nephropathy. Methods: Serum leptin (wire RIA) and serum adiponectin (with ELISA) levels were measured in 34 patients with primary hypertensive nephropathy, in 50 patients with essential hypertension but no nephropathy, as well as in 35 controls. Results: Serum leptin levels in the patients were significantly higher than those in controls (P<0.01). While the serum adiponectin levels were significantly lower than those in controls (P<0.01 ). Among the patients, serum leptin levels were significantly higher in subject with nephropathy than those in subjects without nephropathy (P<0.05) while the reverse was true for adiponectin (P<0.05). Conclusion: The development of primary hypertensive nephropathy is correlated with a higher serum leptin and a decreased serum adiponectin levels. (authors)

  4. Prevalence & Risk Factors of Nephropathy in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Vimalkumar V K

    2011-08-01

    Full Text Available Background: 31.7 million people in India are suffering from diabetes. Diabetic nephropathy (Kimmelstiel-Wilson syndrome is the leading cause of end-stage renal disease (ESRD worldwide and a leading cause of DM-related morbidity and mortality. It is estimated that 79.4 million diabetic patients will be in India by 2030. So a study was done on the prevalence rate of diabetic nephropathy (DN and its associated risk factors.Aims and Objectives: This study is a small cross sectional study conducted in a tertiary hospital (Dr. Ambedkar institute of diabetes, Kilpauk medical college hospital, Chennai.. The objective is to analyze the prevalence of DN and to determine the factors leading to DN in type 2 diabetic patients (mainly containing urban Asian Indian populationMaterials and Methods: 200 Type 2 diabetic patients were randomly selected. All the patients were interviewed with a questionnaire. A detailed history including risk factors like age ,sex , socio economic status, duration of diabetes , smoking , alcohol , family history of DM and kidney disease, Ischemic heart disease(IHD, Oral Hypoglycemic Drugs(OHA , Insulin was taken followed by measurement of blood pressure, BMI assessment, urine analysis for albuminuria and microalbuminuria using dipsticks, lipid profile, GFR estimation, retinopathy screening. Statistical analysis was done by SPSS software. Univariate analysis, Chi-square and Binary Logistic Regression Model was used.Results: In this study prevalence rate of overt nephropathy is 2.5% and microalbuminuria is 13%, Using Binary logistic regression analysis, Woman gender, Duration of diabetes, family history of kidney disease, Hypertension, BMI, GFR, retinopathy were found to be significantly associated with overt DN. There was no increased risk among IHD patients, smokers, alcoholics and no significant relationship with treatment history.Limitations: This is a hospital based cross sectional study. Population based Case control studies

  5. Concomitant macro and microvascular complications in diabetic nephropathy

    International Nuclear Information System (INIS)

    To determine the prevalence of concomitant microvascular and macro vascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 + -11.4 years, mean duration of diabetes was 15.4 + -7.5 years, mean age at the onset of nephropathy was 61.5 + - 12.4 years, and mean duration of nephropathy was 3.9 + - 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate

  6. Improvement of the method of obtaining human IgA Fc-fragments

    Directory of Open Access Journals (Sweden)

    O. Y. Galkin

    2015-02-01

    Full Text Available To address a number of fundamental and applied problems in immunology, molecular and cellular biology and biotechnology it is necessary to obtain Fc-fragments of immunoglobulins. Fc-fragments may be used for studying of the effector functions of antibodies which are mediated by these areas. They are often used as an immunogen to produce anti-specie (based on so-called secondary antibody conjugate in the development of serological tests for diagnostics (predominantly such conjugate based on monoclonal antibodies. The work is aimed to develop improved methods of obtaining and allocation of Fc-fragments of human IgA. To achieve this objective, optimization of hydrolysis of IgA with subsequent purification of Fс-fragments have been carried out. Improved method of obtaining Fc-fragments of IgA provides: papain hydrolysis of immunoglobulin in the environment of nitrogen for 4 h, allowing to achieve maximum output of Fc-fragments without their further degradation: isolation and purification of Fc-fragments of human IgA by one-stage gel filtration on sephadex G-100; control of purity of the target product by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate and Ouchterlony immunodiffusion. Enzymatic hydrolysis was carried out at the optimal temperature of papain (37 °C. As the oxygen in the air may have inhibitory effect on enzymatic hydrolysis reaction, the reaction mixture was incubated in the nitrogen atmosphere to prevent inactivation of papain. To reduce the incident degradation of immunoglobulin molecules, papain hydrolysis was carried out without using an enzyme activator (cysteine. Usage of the proposed scheme allows obtaining Fc-fragments of human IgA of high purity. Outcome of Fc-fragments after all stages of purification was about 18% of the initial amount of IgA in the preparation. Molecular weight from Fc-fragments of human IgA was equal to approximately 70 kDa.

  7. Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Ahuja, Monica; Rai, Taranjit Singh;

    2008-01-01

    .23-16.31). Haplotype with all the wild alleles (T-b-G) was found to be associated with a decreased risk of nephropathy (OR: 0.68, P = 0.005) and haplotype with all mutant alleles (C-a-T) was associated with higher risk of diabetic nephropathy as compared to diabetes without nephropathy group (OR: 2.6, P = 0.14). No...

  8. Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey

    OpenAIRE

    Jae Hee Ahn; Ji Hee Yu; Seung-Hyun Ko; Hyuk-Sang Kwon; Dae Jung Kim; Jae Hyeon Kim; Chul Sik Kim; Kee-Ho Song; Jong Chul Won; Soo Lim; Sung Hee Choi; Kyungdo Han; Bong-Yun Cha; Nan Hee Kim

    2014-01-01

    Background Diabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR), and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and de...

  9. Analysis of a Urinary Biomarker Panel for Obstructive Nephropathy and Clinical Outcomes

    OpenAIRE

    Yuanyuan Xie; Wei Xue; Xinghua Shao; Xiajing Che; Weijia Xu; Zhaohui Ni; Shan Mou

    2014-01-01

    OBJECTIVES: To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis. METHODS: A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-...

  10. Childhood psoriasis

    Directory of Open Access Journals (Sweden)

    Dogra Sunil

    2010-01-01

    Full Text Available Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexural involvement is common and guttate type is the characteristic presentation. Whether onset in childhood predicts a more severe form of psoriasis is a matter of controversy, it may cause significant morbidity particularly if it keeps relapsing. Most children have mild form of psoriasis which can be generally treated effectively with topical agents such as emollients, coal tar, corticosteroids, dithranol, calcipotriol etc. according to age and the sites affected. Narrow band UVB is the preferred form of phototherapy in children for moderate to severe disease or in patients not responding to topical therapy alone. Systemic therapies are reserved for more severe and extensive cases that cannot be controlled with topical treatment and/or phototherapy such as severe plaque type, unstable forms like erythrodermic and generalized pustular psoriasis and psoriatic arthritis. There are no controlled trials of systemic therapies in this age group, most experience being with retinoids and methotrexate with favorable results. Cyclosporine can be used as a short-term intermittent crisis management drug. There is an early promising experience with the use of biologics (etanercept and infliximab in childhood psoriasis. Systemic treatments as well as phototherapy have limited use in children due to cumulative dose effects of drugs, low acceptance, and risk of gonadal toxicity. More evidence-based data is needed about the effectiveness and long-term safety of topical

  11. Animal model and research on pathogenesis of IgA nephropathy%动物模型与IgA肾病的发病机制研究

    Institute of Scientific and Technical Information of China (English)

    王乾了; 李贵森

    2014-01-01

    AlthoughthepathogenesisofIgAnephropathy(IgAN)isstillunclearyet,multi-hit theory has become an accepted mechanism at present. Based on different pathogenetic mechanisms,a variety of IgAN animal models have been established,including passive immunity model,active immunity model, secondary IgAN model,spontaneous IgAN model,and early onset IgAN model. In this article,features of some representative animal models of IgAN will be reviewed briefly. Besides,a new animal model,namelyα1K1-CD89Tg IgAN mouse model,will also be introduced. These different animal models of IgAN have played important roles in the research on IgAN pathogenesis.%IgA肾病(IgAN)的发病机制仍然不清楚,目前较公认的是多重打击学说。基于不同发病机制,已经建立了多种IgAN的动物模型,包括被动免疫模型,主动免疫模型,继发IgAN模型,以及自发性IgAN模型和早发性IgAN动物模型。本文选择一些具有代表性的IgAN动物模型并就其特点作一简单介绍,同时介绍一种新的动物模型,即α1K1-CD89Tg IgAN小鼠模型。这些不同的IgAN动物模型在IgAN发病机制的研究中发挥了重要作用。

  12. Chemical substances as risk factors of nephropathy in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2009-12-01

    Full Text Available Although diabetes mellitus, a metabolic disease, does not fall into the group of diseases induced by toxic substances or environmental pollution, there is much evidence that some chemicals have considerable importance in its development. Exposure to substances with potential renal toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic nephropathy. This paper discusses the relationship between the xenobiotics and the development of diabetes mellitus and diabetic nephropathy with particular emphasis on those substances that causes the greatest damage to the kidneys. These are cadmium, iron, lead, arsenic, polychlorinated organic compounds, nitrogen compounds, and contrast agents. In addition, the mechanisms of diabetes mellitus induction or kidney damage by these xenobiotics are described.

  13. Vesicoureteral Reflux, Reflux Nephropathy, and End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Paul Brakeman

    2008-07-01

    Full Text Available Objective. To review the contribution of vesicoureteral reflux and reflux nephropathy to end-stage renal disease. Data Source. Published research articles and publicly available registries. Results. Vesicoureteral reflux (VUR is commonly identified in pediatric patients and can be associated with reflux nephropathy (RN, chronic kidney disease (CKD, and rarely end-stage renal disease (ESRD. Patients with reduced GFR, bilateral disease, grade V VUR, proteinuria, and hypertension are more likely to progress to CKD and ESRD. Because progression to ESRD is rare in VUR and often requires many decades to develop, there are limited prospective, randomized, controlled trials available to direct therapy to prevent progression to ESRD. Conclusions. Identification of patients with increased risk of progression to CKD and ESRD should be the goal of clinical, biochemical, and radiological evaluation of patients with VUR. Treatment of patients with VUR should be directed at preventing new renal injury and preserving renal function.

  14. Evaluation of reflux nephropathy, pyelonephritis and renal dysplasia

    International Nuclear Information System (INIS)

    MR urography has the potential to significantly improve our understanding of the relationship between reflux nephropathy, pyelonephritis, vesicoureteric reflux and renal dysplasia. MR urography utilizes multiple parameters to assess both renal anatomy and function and provides a more complete characterization of acquired and congenital disease. Pyelonephritis and renal scarring can be distinguished by assessing the parenchymal contours and signal intensity. Characteristic imaging features of renal dysplasia include small size, subcortical cysts, disorganized architecture, decreased and patchy contrast enhancement as well as a dysmorphic pelvicalyceal system. Because of its ability to subdivide and categorize this heterogeneous group of disorders, it seems inevitable that MR urography will replace DMSA renal scintigraphy as the gold standard for assessment of pyelonephritis and renal scarring. MR urography will contribute to our understanding of renal dysplasia and its relationship to reflux nephropathy. (orig.)

  15. Features of endothelial dysfunction in early diabetic nephropathy

    DEFF Research Database (Denmark)

    Jensen, T; Bjerre-Knudsen, J; Feldt-Rasmussen, B; Deckert, T

    1989-01-01

    ); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls. The rise in tPA antigen with exercise was similar in the controls and.......01) and II (difference not significant, p = 0.06) than in group I and normal controls. These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage. It is not yet clear whether these changes are......The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h...

  16. Association of renal adenocarcinoma and BK virus nephropathy post transplantation.

    Science.gov (United States)

    Kausman, Joshua Yehuda; Somers, Gino Rene; Francis, David Michael; Jones, Colin Lindsay

    2004-04-01

    While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health. PMID:14986088

  17. Aplastic anemia and membranous nephropathy induced by intravenous mercury

    OpenAIRE

    Priya, N.; Nagaprabhu, V. N.; Kurian, G.; Seethalakshmi, N.; Rao, G. G.; Unni, V. N.

    2012-01-01

    Self-injection of mercury can be life-threatening. We report a case of attempted suicide by self-intravenous injection of elemental mercury. The patient suffered from two side effects : membranous nephropathy and aplastic anemia. She was treated and the systemic effects of mercury were reversed after 4 years. The toxicology of mercury, mechanisms of renal and systemic toxicities, and the various therapeutic measures for mercury poisoning are discussed.

  18. Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy

    OpenAIRE

    Zurbig, P.; Jerums, G; Hovind, P.; MacIsaac, R.; Mischak, H.; Nielsen, S. E.; Panagiotopoulos, S.; Persson, F.; Rossing, P.

    2012-01-01

    Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventing the need for renal replacement therapy. We evaluated urinary proteome analysis as a tool for prediction of DN. Capillary electrophoresis–coupled mass spectrometry was used to profile the low–mol...

  19. Chronic interstitial nephropathy after plasma cutting in stainless steel.

    OpenAIRE

    Petersen, R.; Mikkelsen, S; Thomsen, O F

    1994-01-01

    Chromium is nephrotoxic in experimental animals. In subjects with acute chromium intoxication acute nephritis has been reported and renal function has been affected in chromium exposed workers with a high urinary chromium concentration. Chronic kidney disease after long term occupational exposure to chromium has, however, not been reported previously. A case report is presented concerning a 48 year old man who was diagnosed with chronic interstitial nephropathy. He had worked for nine years a...

  20. The role of ultrasonography in the study of medical nephropathy

    OpenAIRE

    Fiorini, F.; Barozzi, L.

    2007-01-01

    Diagnostic techniques in nephrology include clinical history, physical examination, laboratory tests, scintigraphy, diagnostic imaging techniques as well as renal biopsy. In kidney diseases, ultrasonography is used as a first-line imaging technique, and its role in medical nephropathy is to exclude urological pathologies, to differentiate between acute and chronic renal failure, to follow-up on the course of a disease, to guide needle biopsy, etc. Ultrasound images are useful at characterizin...

  1. Vitamin E and diabetic nephropathy in mice model and humans

    OpenAIRE

    Farid, Nakhoul; Inbal, Dahan; Nakhoul, Nakhoul; Evgeny, Farber; Miller-Lotan, Rachel; Levy, Andrew P.; Rabea, Asleh

    2013-01-01

    Diabetes mellitus (DM) is associated with increased oxidative stress due to elevated glucose levels in the plasma. Glucose promotes glycosylation of both plasma and cellular proteins with increased risk for vascular events. Diabetic patients suffer from a higher incidence of cardiovascular complications such as diabetic nephropathy. Haptoglobin (Hp) is an antioxidant plasma protein which binds free hemoglobin, thus preventing heme-iron mediated oxidation. Two alleles exist at the Hp gene locu...

  2. [Mechanism of Chinese herbal medicine delaying glomerulosclerosis in diabetic nephropathy].

    Science.gov (United States)

    Chen, Jing; Wan, Yigang; Bian, Rongwen; Gu, Liubao; Wang, Chaojun; Zhang, Huilan; Yao, Jian

    2010-02-01

    The pathomechanisms of glomerulosclerosis in diabetic nephropathy (DN) are considered to be related with glycometabolism disorder, podocyte injury, intra-renal hemodynamics abnormality, fibrogenic cytokines over-expression, oxidative stress and inflammatory reaction. Chinese herbal medicine could delay the progression of glomerulosclerosis in DN by ameliorating the harmful factors of these pathological changes. Therefore, it is possible to postpone the progress of DN to end-stage renal disease through the treatment with Chinese herbal medicine. PMID:20450059

  3. Cholera toxin B suppresses allergic inflammation through induction of secretory IgA.

    Science.gov (United States)

    Smits, H H; Gloudemans, A K; van Nimwegen, M; Willart, M A; Soullié, T; Muskens, F; de Jong, E C; Boon, L; Pilette, C; Johansen, F-E; Hoogsteden, H C; Hammad, H; Lambrecht, B N

    2009-07-01

    In healthy individuals, humoral immune responses to allergens consist of serum IgA and IgG4, whereas cellular immune responses are controlled by regulatory T (Treg) cells. In search of new compounds that might prevent the onset of allergies by stimulating this type of immune response, we have focused on the mucosal adjuvant, cholera toxin B (CTB), as it induces the formation of Treg cells and production of IgA. Here, we have found that CTB suppresses the potential of dendritic cells to prime for Th2 responses to inhaled allergen. When we administered CTB to the airways of naïve and allergic mice, it strongly suppressed the salient features of asthma, such as airway eosinophilia, Th2 cytokine synthesis, and bronchial hyperreactivity. This beneficial effect was only transferable to other mice by transfer of B but not of T lymphocytes. CTB caused a transforming growth factor-beta-dependent rise in antigen-specific IgA in the airway luminal secretions, which was necessary for its preventive and curative effect, as all effects of CTB were abrogated in mice lacking the luminal IgA transporting polymeric Ig receptor. Not only do these findings show a novel therapeutic avenue for allergy, they also help to explain the complex relationship between IgA levels and risk of developing allergy in humans. PMID:19404246

  4. Phagocytosis of IgA Immune Complexes by Human U937 Cells

    Institute of Scientific and Technical Information of China (English)

    郭彩云; 崔薇; 张伟

    2003-01-01

    In order to study FcαR Ⅰ mediated phagocytosis ot lgA immune complexes by U937 cells, antigen 8.9NIP/BSA was labeled with FITC and reacted with anti-NIP IgA or anti-NIP IgG antibody to form immune complexes (ICs). They were then incubated with phorbol 12-myristate B-acetate (PMA) stimulated U937 cells. The phagocytosed ICs were quantified by flow cytometry. The results was that the expression of FcαR Ⅰ on U937 cells was higher than that of FcγR Ⅰ , FcyR Ⅱ and FcγR Ⅲ. After stimulation by PMA, expression of FcαR Ⅰ on U937 cells was markedly upregulated and the phagocytosis of IgA ICs was enhanced. FcαR Ⅰ mediated specific IgA phagocytosis was stronger than FcγR Ⅰ and FcγR Ⅱ mediated IgG phagocytosis. Complement receptors, CR1 and CR3, enhanced U937 cell phagocytosis of IgA ICs. It concludes that FcγR Ⅰ mediated strong phagocytosis of IgA ICs.

  5. A novel human IgA monoclonal antibody protects against tuberculosis.

    Science.gov (United States)

    Balu, Sucharitha; Reljic, Rajko; Lewis, Melanie J; Pleass, Richard J; McIntosh, Richard; van Kooten, Cees; van Egmond, Marjolein; Challacombe, Stephen; Woof, Jenny M; Ivanyi, Juraj

    2011-03-01

    Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the mycobacterial α-crystallin Ag and for the human FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-γ significantly inhibited pulmonary H37Rv infection in mice transgenic for human CD89 but not in CD89-negative littermate controls, suggesting that binding to CD89 was necessary for the IgA-imparted passive protection. 2E9IgA1 added to human whole-blood or monocyte cultures inhibited luciferase-tagged H37Rv infection although not for all tested blood donors. Inhibition by 2E9IgA1 was synergistic with human rIFN-γ in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of FcαRI (CD89) for human IgA-mediated protection is important for understanding of the mechanisms involved and also for translation of this approach toward development of passive immunotherapy of tuberculosis. PMID:21257971

  6. Childhood obesity.

    Science.gov (United States)

    Han, Joan C; Lawlor, Debbie A; Kimm, Sue Y S

    2010-05-15

    Worldwide prevalence of childhood obesity has increased greatly during the past three decades. The increasing occurrence in children of disorders such as type 2 diabetes is believed to be a consequence of this obesity epidemic. Much progress has been made in understanding of the genetics and physiology of appetite control and from these advances, elucidation of the causes of some rare obesity syndromes. However, these rare disorders have so far taught us few lessons about prevention or reversal of obesity in most children. Calorie intake and activity recommendations need reassessment and improved quantification at a population level because of sedentary lifestyles of children nowadays. For individual treatment, currently recommended calorie prescriptions might be too conservative in view of evolving insight into the so-called energy gap. Although quality of research into both prevention and treatment has improved, high-quality multicentre trials with long-term follow-up are needed. Meanwhile, prevention and treatment approaches to increase energy expenditure and decrease intake should continue. Recent data suggest that the spiralling increase in childhood obesity prevalence might be abating; increased efforts should be made on all fronts to continue this potentially exciting trend. PMID:20451244

  7. Crystallographic investigationsof urine at newborns with ischemic nephropathy

    Directory of Open Access Journals (Sweden)

    Loboda A.

    2012-01-01

    Full Text Available The study is devoted to the identification of structural markers of ischemic nephropathy by studying facies (dry drops of urine in newborn infants. The study involved two groups of full-term newborns with gestational age 38-41 weeks and signs of ischemic nephropathy: 1st - 75 children who suffered severe asphyxia, 2nd - 75 children with moderate asphyxia. Comparison group consisted of 20 infants without asphyxia at birth. Morphological changes were detected in dry drops by microscopy at 40-fold increase in 1-2 and 7-8 days of life. Asphyxia cause disturbance of renal filtration, tubular reabsorption and secretion that lead to increase levels of organic components and mineral salts in urine, crystallization of which forms a specific picture of facies. By urine’s facies morphology at 1-2 days of life is possible to evaluate renal function in newborns suffered from asphyxia. The number of inclusions in facies, their total area and distribution are depending on the severity of asphyxia. Structural changes in the urine of children with ischemic nephropathy remain till the end of the early neonatal period.

  8. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alejandra Guillermina Miranda-Díaz

    2016-01-01

    Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

  9. Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ramdas Pandhare

    2012-09-01

    Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

  10. Iodinated contrast agent-induced nephropathy; Mit jodhaltigen Kontrastmitteln induzierte Nephropathie

    Energy Technology Data Exchange (ETDEWEB)

    Erley, C. [St. Joseph-Krankenhaus Berlin, Berlin (Germany)

    2007-09-15

    Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management. A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.). (orig.) [German] Die Kontrastmittelnephropathie (contrast

  11. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    International Nuclear Information System (INIS)

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH2-CH = O), L5 lipids (-CH2-C = O), and L3 lipids (-CH2-CH2-C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research. These

  12. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  13. Regulation of IgA responses in cattle, humans and mice.

    Science.gov (United States)

    Estes, D Mark

    2010-12-15

    Secretory IgA (SIgA) constitutes the largest component of the humoral immune system of the body with gram quantities of this isotype produced by mammals on a daily basis. Secretory IgA (SIgA) antibodies function by both blocking pathogen/commensal entry at mucosal surfaces and virus neutralization. Several pathways of induction of IgA responses have been described which depend on T cells (T cell dependent or TD) pathways or are independent of T cells (T-independent or TI) and are mediated by dendritic cells (DCs) and/or epithelial cells. Many elements of IgA regulation readily cross species barriers (adjuvants, soluble and cognate factors) and are highly conserved whereas other pathways may be more specific to any given species and must be evaluated. Regulation of IgA production in cattle is not completely understood and thus we have focused in part on highly conserved factors such as transforming growth factor beta, Type I and Type 2 interferons, neuropeptides which interdigitate mucosal tissues (vasoactive intestinal peptide or VIP), and a small peptide (IgA inducing peptide or IGIP) which can serve as targets for modulation and increasing SIgA virus-specific antibodies. We have evaluated the potential utility of modulating these factors in vitro in regulation of qualitative aspects of antibodies of the IgM, IgG and IgA isotypes at mucosal surfaces and in secretions of the upper and lower respiratory tract to a virus of economic and public health importance, foot and mouth disease virus (FMDV). IgA responses in cattle are essential for host defense in response to various infectious agents. In cattle, IgA is not released into the colostrum, as is the case for other mammals but only IgG1 is selectively transported. In previous studies in cattle, IgA has been shown to be regulated by several cytokines including IFN-gamma, Type I interferons such as IFN-alpha and IFN-tau, transforming growth factor beta, IgA inducing peptide and other potential factors such as APRIL

  14. The susceptibility of Candu steam generator tubing alloys to IGA/IGSCC in acid sulphate environments

    International Nuclear Information System (INIS)

    Constant extension rate tests (CERT) were carried out to assess the susceptibility of CANDU steam generator (SG) tube materials to intergranular stress corrosion cracking (IGSCC) in acidified sulphate solutions calculated to exist in SG crevices following sulphuric acid and Lake Huron water ingress. The results indicate significant susceptibility of Alloy 600 tubing (i.e. Bruce A) to IGSCC following sulphuric acid ingress and some susceptibility to intergranular attack (IGA) following Lake Huron water ingress. Alloy 800 was slightly susceptible to IGA in sulphuric acid ingress crevice chemistries but not at all to Lake Huron water ingress crevice chemistry. Alloy 690 was not susceptible to IGSCC or IGA in any of the chemistries tested. Preliminary results suggest that lead contamination of 1000 ppm does not increase the susceptibility of any of the Alloys tested to IGSCC following sulphuric acid ingress. (authors). 3 figs., 2 tabs., 6 refs

  15. Circulating IgA immune complexes in patients with psoriasis

    International Nuclear Information System (INIS)

    The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p . 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis

  16. Directional dominance for low IgM and IgA levels.

    OpenAIRE

    Clark, P.; Jardine, R.; Jones, P.; Martin, N G; Walsh, R J

    1981-01-01

    A biometrical genetical analysis of IgG, IgM, and IgA levels in 134 sets of twins is reported. High heritabilities, around .8, are found for all three immunoglobulin levels, and possible reasons for lower heritabilities found in family studies are discussed. There is evidence for genetical dominance tending to decrease IgM and IgA levels, but there is no evidence for the importance of family environment although the presence of dominance may make its detection difficult. The causes of covaria...

  17. The Role of Interleukin-6 in Mucosal IgA Antibody Responses in Vivo

    Science.gov (United States)

    Ramsay, Alistair J.; Husband, Alan J.; Ramshaw, Ian A.; Bao, Shisan; Matthaei, Klaus I.; Koehler, Georges; Kopf, Manfred

    1994-04-01

    In mice with targeted disruption of the gene that encodes interleukin-6 (IL-6), greatly reduced numbers of immunoglobulin A (IgA)-producing cells were observed at mucosae and grossly deficient local antibody responses were recorded after mucosal challenge with either ovalbumin or vaccinia virus. The IgA response in the lungs was completely restored after intranasal infection with recombinant vaccinia viruses engineered to express IL-6. These findings demonstrate a critical role for IL-6 in vivo in the development of local IgA antibody responses and illustrate the effectiveness of vector-directed cytokine gene therapy.

  18. Structural requirements for the interaction of human IgA with the human polymeric Ig receptor.

    Science.gov (United States)

    Lewis, Melanie J; Pleass, Richard J; Batten, Margaret R; Atkin, Julie D; Woof, Jenny M

    2005-11-15

    Transport of polymeric IgA onto mucosal surfaces to become secretory IgA is mediated by the polymeric Ig receptor (pIgR). To study the interaction of human dimeric IgA (dIgA) (the predominant form of IgA polymer) with the human pIgR (hpIgR), we generated recombinant wild-type dIgA1 and dIgA2m(1) and various mutant dIgA1 and analyzed their interaction with a recombinant human secretory component and membrane-expressed hpIgR. We found that wild-type dIgA1 and dIgA2m(1) bound to recombinant human secretory component with similar affinity and were transcytosed by the hpIgR to the same extent. Mutation of the IgA Calpha2 domain residue Cys311 to Ser reduced binding to hpIgR, possibly through disruption of noncovalent interactions between the Calpha2 domain and domain 5 of the receptor. Within the Calpha3 domain of IgA1, we found that combined mutation of residues Phe411, Val413, and Thr414, which lie close to residues previously implicated in hpIgR binding, abolished interaction with the receptor. Mutation of residue Lys377, located very close to this same region, perturbed receptor interaction. In addition, 4 aa (Pro440-Phe443), which lie on a loop at the domain interface and form part of the binding site for human FcalphaRI, appear to contribute to hpIgR binding. Lastly, use of a monomeric IgA1 mutant lacking the tailpiece revealed that the tailpiece does not occlude hpIgR-binding residues in IgA1 monomers. This directed mutagenesis approach has thus identified motifs lying principally across the upper surface of the Calpha3 domain (i.e., that closest to Calpha2) critical for human pIgR binding and transcytosis. PMID:16272325

  19. Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians

    DEFF Research Database (Denmark)

    Cheema, Balneek Singh; Iyengar, Sreenivasa; Ahluwalia, Tarun Veer Singh;

    2012-01-01

    genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic...

  20. [Lupus nephropathy in childhood and familial lupus. Genetic study of a family].

    Science.gov (United States)

    Gómez Campdera, F J; Yebra, M; Vicario, J L; Rodríguez, M; Rengel, M; Manzano, L; Martín Villa, J M; Gutiérrez, C

    1989-04-15

    We report a case of a 14 1/2-year-old boy who was diagnosed of systemic lupus erythematosus in the background of an acute nephritic syndrome, 3 1/2 years after being diagnosed of idiopathic thrombocytopenic purpura. The familial history suggested the presence of other cases of SLE, which were proven with relevant clinical and laboratory studies. A genetic study for disease markers was carried out and a correlation was found with haplotypes HLA A25, B18, BW6, DRX, and DQW; C2 deficiency was ruled out. We conclude that it is of paramount importance to rule out the existence of familial SLE in front of infantile SLE, particularly in boys, and we emphasize the necessity of keeping on further searching for genetic markers of the disease. PMID:2755225

  1. Characterization of the ligand binding site of the bovine IgA Fc receptor (bFc alpha R).

    Science.gov (United States)

    Morton, H Craig; Pleass, Richard J; Woof, Jenny M; Brandtzaeg, Per

    2004-12-24

    Recently, we identified a bovine IgA Fc receptor (bFc alpha R), which shows high homology to the human myeloid Fc alpha R, CD89. IgA binding has previously been shown to depend on several specific residues located in the B-C and F-G loops of the membrane-distal extracellular domain 1 of CD89. To compare the ligand binding properties of these two Fc alpha Rs, we have mapped the IgA binding site of bFc alpha R. We show that, in common with CD89, Tyr-35 in the B-C loop is essential for IgA binding. However, in contrast to earlier observations on CD89, mutation of residues in the F-G loop did not significantly inhibit IgA binding. PMID:15485844

  2. TGF-β1 improves mucosal IgA dysfunction and dysbiosis following intestinal ischaemia-reperfusion in mice.

    Science.gov (United States)

    Zhang, Xu-Yu; Liu, Zi-Meng; Zhang, Hu-Fei; Li, Yun-Sheng; Wen, Shi-Hong; Shen, Jian-Tong; Huang, Wen-Qi; Liu, Ke-Xuan

    2016-06-01

    Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF)-β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF-β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF-β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF-β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria-binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor-β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF-β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB-431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF-β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF-β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF-β receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF-β1. PMID:26820382

  3. Historical chronology of basic and clinical research in diabetic nephropathy and contributions of Japanese scientists.

    Science.gov (United States)

    Wada, Jun; Makino, Hirofumi

    2009-10-01

    The most problematic issue in clinical nephrology worldwide is the relentless and progressive increase in patients with end-stage renal disease (ESRD). Diabetic nephropathy has considerable impact on society in the areas of public health and social economy; many scientists are involved in research for the elucidation of the pathogenesis of diabetic nephropathy and for the prevention and cure of the disease. In contrast, diabetic nephropathy was a neglected or ignored disease in the historical era, and few dedicated physicians recognized the disease process of diabetic nephropathy. In this review, we look back on the history of basic and clinical research on diabetic nephropathy and survey the recent progress of the research, especially focusing on the contribution of Japanese scientists. PMID:19363645

  4. Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

    Directory of Open Access Journals (Sweden)

    Anubhav Thukral

    2011-01-01

    Full Text Available Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

  5. How Are Childhood Cancers Found?

    Science.gov (United States)

    ... Topic How are childhood cancers treated? How are childhood cancers found? Screening for childhood cancers Screening is testing for a disease such ... in people who don’t have any symptoms. Childhood cancers are rare, and there are no widely ...

  6. The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats.

    Science.gov (United States)

    Al-Malki, Abdulrahman L; El Rabey, Haddad A

    2015-01-01

    The antidiabetic activity of two low doses of Moringa seed powder (50 and 100 mg/kg body weight, in the diet) on streptozotocin (STZ) induced diabetes male rats was investigated. Forty rats were divided into four groups. The diabetic positive control (STZ treated) group showed increased lipid peroxide, increased IL-6, and decreased antioxidant enzyme in the serum and kidney tissue homogenate compared with that of the negative control group. Immunoglobulins (IgA, IgG), fasting blood sugar, and glycosylated hemoglobin (HbA1c) were also increased as a result of diabetes in G2 rats. Moreover albumin was decreased, and liver enzymes and α-amylase were not affected. In addition, the renal functions and potassium and sodium levels in G2 were increased as a sign of diabetic nephropathy. Urine analysis showed also glucosuria and increased potassium, sodium, creatinine, uric acid, and albumin levels. Kidney and pancreas tissues showed also pathological alteration compared to the negative control group. Treating the diabetic rats with 50 or 100 mg Moringa seeds powder/kg body weight in G3 and G4, respectively, ameliorated the levels of all these parameters approaching the negative control values and restored the normal histology of both kidney and pancreas compared with that of the diabetic positive control group. PMID:25629046

  7. Alterations of urinary metabolite profile in model diabetic nephropathy

    International Nuclear Information System (INIS)

    Highlights: • 1H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS−/− C57BLKS and eNOS−/− C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS−/− C57BLKS and eNOS−/− C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in metabolomic

  8. Effect of pregnancy on diabetic nephropathy and retinopathy

    International Nuclear Information System (INIS)

    Objective: To determine whether pregnancy worsens renal function in women with diabetic nephropathy and the effect of pregnancy on diabetic retinopathy. Subject and Methods: Thirty-five patients (aged 20-36 years) identified with diabetic nephropathy and moderate to severe renal dysfunction (creatinine Cr) - > 1.4 mg/dl) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate (GFR) were estimated. An equal number of non-pregnant premenopausal type I diabetic women with similar degrees of renal dysfunction served as controls for non-pregnant rate of decline of renal function and potential contributing factors. Student's t-test and repeated measures analysis of variance were analyzed. Results: Mean serum Cr rose from 1.8 mg/dl pre pregnancy to 2.5 mg/dl in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or pre-eclampsia occurred in 73% and 71% of these showed acceleration of disease during the pregnancy. All the patients had diabetic retinopathy, though proliferative retinopathy was diagnosed and treated in only 54.5.% pre pregnancy. The retinopathy progressed, requiring laser therapy, in 45.4%. Macular edema was noted in 6 of the patients. Other diabetic complications included peripheral and autonomic neuropathy in 8 patients. Conclusion: Pregnancy induced progression is seen in the decline of renal functions. Patients with diabetic nephropathy were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy. Forty-five percent of the patients had permanent decline in GFR in association with pregnancy. (author)

  9. Inducement of IGA/SCC in Inconel 600 steam generator tubing during unit outages

    International Nuclear Information System (INIS)

    The degradation of Unit 4 SG tubing by IGA/SCC has limited both the operating period and end of life predictions for Unit 4 since restart in late 2003. The circumferential IGA/SCC has been most significant in SG4 with substantial increases in both initiation and growth rates from 2005 through the spring of 2007. A detailed review of the occurrence of circumferential OD IGA/SCC at the RTZ in the HL TTS region of Bruce 4 steam generator tubes has led a conclusion that it is probable that the IGA/SCC has been the result of attack by partially reduced sulfur species such as tetrathionates and thiosulfates during periods of low temperature exposure. It is believed that attack of this type has mostly likely occurred during startup evolutions following outages as the result the development of aggressive reduced sulfur species in the TTS region during periods when the boilers were fully drained for maintenance activities. The modification of outage practices to limit secondary side oxygen ingress in the spring of 2007 has apparently arrested the degradation and has had significant affects on the allowable operating interval and end of life predictions for the entire unit. (author)

  10. IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production.

    Science.gov (United States)

    Jung, Y; Wen, T; Mingler, M K; Caldwell, J M; Wang, Y H; Chaplin, D D; Lee, E H; Jang, M H; Woo, S Y; Seoh, J Y; Miyasaka, M; Rothenberg, M E

    2015-07-01

    Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double deficient or CC chemokine receptor 3 deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer's patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1β (IL-1β), inducible nitric oxide synthase, lymphotoxin (LT) α, and LT-β, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-γt(+)) innate lymphoid cells (ILCs), while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell-activating factor of the tumor necrosis factor family), and TGF-β (transforming growth factor β). GI eosinophils expressed a relatively high level of IL-1β, and IL-1β-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA(+) cells and ROR-γt(+) ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1β in the small intestine. PMID:25563499

  11. Development of a new immunochromatographic assay using gold nanoparticles for screening of IgA deficiency.

    Directory of Open Access Journals (Sweden)

    Saeid Goudarzi

    2015-02-01

    Full Text Available A new competitive immunochromatography (ICG strip test based on polyclonal antibody (pAb conjugated with gold nanoparticles (NPs was developed and its applications for primary screening of immunoglobulin (Ig A in serum were evaluated. Nanocolloidal gold as the detection reagent, with an average particle diameter of 20 nm, was synthesized and labelled pAb. The antibody-nanocolloidal gold probe was applied on the conjugate pad, and human IgA was immobilized on a nitrocellulose membrane as the capture reagent to prepare the ICG strip test. It took only 10 minutes to accomplish a semi-quantitative detection of serum IgA in this assay. In the optimized investigational conditions, the ICG strip test could distinguish human serum IgA in the range from 1 to 270 ng/mL with a detection limit of 5 ng/mL. The reliability of testing procedures was examined by performing the ICG strip test with 11 serum samples and comparing the results with those obtained via enzyme-linked immunosorbent assay (ELISA. The ICG strip was sufficiently sensitive and accurate for a rapid screening of IgA in human serum.

  12. Iga tööotsija saab isikliku tegutsemiskava / Eva Kübar

    Index Scriptorium Estoniae

    Kübar, Eva

    2006-01-01

    Alates 2006. aastast saab iga töötu isikliku tööotsimiskava, mille täitmist hakkab jälgima tööturuamet. Lisa: Individuaalne tööotsimiskava. Ilmunud ka: ; Postimees : na russkom jazõke 4. jaan. lk. 3

  13. Iga nädal pankrotistub mitu ehitusfirmat / Liis Kängsepp

    Index Scriptorium Estoniae

    Kängsepp, Liis, 1981-

    2008-01-01

    Kinnisvarabuumi ajal loodud firmade seas on kasvanud pankrottide arv, pea iga nädal läheb pankrotti mõni ehitus-, kinnisvara- või mööblifirma. Vt. samas: Lepik: hullem on ees; Pankrotihaldur: elatakse üle võimete. Diagramm: Pankrotistunud ehitusfirmad

  14. Cholera toxin B suppresses allergic inflammation through induction of secretory IgA

    NARCIS (Netherlands)

    H.H. Smits; A.K. Gloudemans; M. van Nimwegen; M.A. Willart; T. Soullié; F. Muskens; E.C. de Jong; L. Boon; C. Pilette; F.E. Johansen; H.C. Hoogsteden; H. Hammad; B.N. Lambrecht

    2009-01-01

    In healthy individuals, humoral immune responses to allergens consist of serum IgA and IgG4, whereas cellular immune responses are controlled by regulatory T (Treg) cells. In search of new compounds that might prevent the onset of allergies by stimulating this type of immune response, we have focuse

  15. Bacteria as a target of human milk and myeloma IgA

    Czech Academy of Sciences Publication Activity Database

    Přibylová, Jaroslava; Moldoveanu, Z.; Mestecky, J.; Tlaskalová, Helena

    2009-01-01

    Roč. 39, - (2009), s. 760-760. ISSN 0014-2980. [European Congress of Immunology /2./. 13.09.2009-16.09.2009, Berlin] Institutional research plan: CEZ:AV0Z50200510 Keywords : human milk * myeloma IgA Subject RIV: EC - Immunology

  16. Childhood medulloblastoma.

    Science.gov (United States)

    Massimino, Maura; Biassoni, Veronica; Gandola, Lorenza; Garrè, Maria Luisa; Gatta, Gemma; Giangaspero, Felice; Poggi, Geraldina; Rutkowski, Stefan

    2016-09-01

    Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk. PMID:27375228

  17. Long-term prevention of diabetic nephropathy: an audit

    DEFF Research Database (Denmark)

    Schjoedt, K.J.; Hansen, H.P.; Tarnow, L.;

    2008-01-01

    AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin......-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227) in...

  18. Childhood Brain Tumors

    Science.gov (United States)

    ... They are among the most common types of childhood cancers. Some are benign tumors, which aren't ... can still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches ...

  19. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  20. Childhood Overweight and Obesity

    Science.gov (United States)

    ... Childhood Obesity Facts The prevalence of obesity among low-income children aged 2 through 4 years, by state ... Obesity now affects 1 in 6 children and adolescents in the United States. Childhood Obesity Facts How ...

  1. Reducing Childhood Obesity

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... page please turn Javascript on. The We Can! childhood obesity-prevention program involves parents, caregivers, and community leaders ...

  2. The Evaluation of Psychological Factor and Salivary Cortisol and IgA Levels in

    Directory of Open Access Journals (Sweden)

    Fateme Arbabi-Kalati

    2014-07-01

    Full Text Available Background: Oral lichen planus (OLP is a chronic immunological disorder with unknown etiology. The aim of this study was to determine psychological factors and salivary cortisol, IgA level in patients with oral lichen planus. Materials and Methods: In this experimental study 20 patients with OLP and healthy person were admitted to this study. Saliva samples were collected between - Am. saliva cortisol, IgA level was detected by ELIZA method. In this study, patients with anxiety and depression were measured using the SCL-90 questionnaire. Data analyzed by t-test. Results: The mean salivary cortisol level in patients with OLP was 3.2±1.9 ng/mL and the mean saliva cortisol level in healthy person was 3.5±1.9 ng/mL. Significant difference was observed in the salivary cortisol levels in the 2 study groups (p=0.04. The mean salivary IgA level in patients with OLP was 0.69±0.29 ng/mL and the mean saliva IgA level in healthy person was 0.9±0.43 ng/mL but no significant difference was observed in the salivary cortisol levels in the 2 study groups. Results showed that anxiety levels in patients with oral lichen planus were slightly higher than controls but there was no significant difference between healthy subjects. Conclusion: Finding revealed the mean salivary cortisol level in patient with OLP less than healthy persons. Significant difference was observed in the salivary cortisol levels in the 2 study groups. Based on the t-student test, no significant difference was observed in the salivary IgA levels in the 2 study groups. Anxiety levels in patients with oral lichen planus were slightly higher than controls.

  3. Intra-tumour IgA1 is common in cancer and is correlated with poor prognosis in bladder cancer.

    Science.gov (United States)

    Welinder, Charlotte; Jirström, Karin; Lehn, Sophie; Nodin, Björn; Marko-Varga, György; Blixt, Ola; Danielsson, Lena; Jansson, Bo

    2016-08-01

    A high frequency of IgA1-positive tumour cells was found in tissue micro-arrays of oesophagus, colon, testis, lung, breast, bladder and ovarian cancer. IgA1 was observed in the cytoplasm and the plasma membrane. A correlation was found between intra-tumour IgA1 and poor overall survival in a large cohort of bladder cancer patients (n = 99, p = 0.011, log-rank test). The number of IgA1-positive tumour cells was also found to be higher in female than male bladder cancer patients. The presence of IgA1 was confirmed in formalin-fixed paraffin-embedded ovarian carcinoma samples using LC-MS/MS analysis. Uptake of IgA1 was also observed in breast cancer and melanoma cell lines when cultivated in the presence of serum from healthy individuals, indicating a possible origin of the IgA1 antibodies in cancer cells. PMID:27579449

  4. Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy.

    Science.gov (United States)

    Wang, Bin; Liu, Ding; Zhu, Qiu-Hua; Li, Min; Chen, Hua; Guo, Ying; Fan, Li-Pei; Yue, Liang-Sheng; Li, Liu-Yang; Zhao, Ming

    2016-06-01

    Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-β1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-β1/Smad3 signaling. PMID:27035719

  5. Pyelonephritis, renal scarring, and reflux nephropathy: a pediatric urologist's perspective

    International Nuclear Information System (INIS)

    Imaging of children with a clinical diagnosis of pyelonephritis is performed to characterize the extent of the infection, to identify associated renal injury and to uncover risk factors for future infections and renal damage. Although there is general agreement regarding the need for parenchymal imaging and the need to exclude processes that are either functionally or anatomically obstructive, there is controversy regarding the need for routine cystography, especially when parenchymal involvement has not been documented. A protocol that limits the use of cystography for evaluation of urinary tract infections must assume that the diagnosis of reflux is at least of variable clinical significance. It is now clear that vesicoureteral reflux and reflux nephropathy represent a diverse population that includes both congenital and acquired processes. MR imaging will improve our understanding of vesicoureteral reflux, pyelonephritis and renal scarring and might help us to identify and manage those patients most at risk for recurrent infections and renal injury. To recognize the potential contributions of this newer imaging technique it is helpful to look at our understanding of the pathophysiology of pyelonephritis, reflux and reflux nephropathy. (orig.)

  6. Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology?

    Science.gov (United States)

    Murray, Kristy O; Fischer, Rebecca S B; Chavarria, Denis; Duttmann, Christiane; Garcia, Melissa N; Gorchakov, Rodion; Hotez, Peter J; Jiron, William; Leibler, Jessica H; Lopez, Job E; Mandayam, Sreedhar; Marin, Alejandro; Sheleby, Jessica

    2015-10-01

    An outbreak of unexplained and severe kidney disease, "Mesoamerican Nephropathy," in mostly young, male sugar cane workers emerged in Central America in the late 1990's. As a result, an estimated 20,000 individuals have died, to date. Unfortunately, and with great consequence to human life, the etiology of the outbreak has yet to be identified. The sugarcane fields in Chichigalpa, Chinandega, Nicaragua, have been involved in the outbreak, and during our initial investigation, we interviewed case patients who experienced fever, nausea and vomiting, arthralgia, myalgia, headache, neck and back pain, weakness, and paresthesia at the onset of acute kidney disease. We also observed a heavy infestation of rodents, particularly of Sigmodon species, in the sugarcane fields. We hypothesize that infectious pathogens are being shed through the urine and feces of these rodents, and workers are exposed to these pathogens during the process of cultivating and harvesting sugarcane. In this paper, we will discuss the epidemic in the Chichigalpa area, potential pathogens responsible for Mesoamerican Nephropathy, and steps needed in order to diagnose, treat, and prevent future cases from occurring. PMID:26320026

  7. Effect of antihypertensive treatment on progression of incipient diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    The aim of the study was to clarify whether antihypertensive treatment with a selective beta blocker would have an effect on the progression rate of kidney disease in patients with incipient diabetic nephropathy. Six male patients with juvenile-onset diabetes with incipient nephropathy (urinary...... albumin excretion above 15 micrograms/min and total protein excretion below 0.5 g/24 hr) were treated with metoprolol (200 mg daily). At the start of the antihypertensive treatment the mean age was 32 years +/- 4.2 (SD). The patients were followed a mean 5.4 years +/- 3.1 (SD) with repeated measurements...... of urinary albumin excretion before and during 2.6 years +/- 1.0 (SD) of treatment. The blood pressure was depressed by the treatment (systolic blood pressure from 135 mm Hg +/- 8.6 to 124 mm Hg +/- 6.2, NS; mean blood pressure from 107 mm Hg +/- 7.6 to 97 mm Hg +/- 3.4, 2p less than 0.05; diastolic...

  8. ACE Gene Insertion/Deletion Polymorphism and Type-2 Diabetic Nephropathy in Eastern Indian Population

    Directory of Open Access Journals (Sweden)

    Mithun Sikdar

    2013-02-01

    Full Text Available Background: Nephropathy is one of the major complications among the patients having type 1 or long term Type 2 diabetes and there are various studies that suggest its genetic predisposition. A 287 bp insertion/deletion (I/D polymorphism of the gene encoding angiotensin-I converting enzyme (ACE is shown to have association with diabetic nephropathy. Aim: To identify the association of ACE I/D polymorphism with subjects having diabetic nephropathy.Materials and methods: The present study examined the prevalence of ACE insertion/deletion polymorphism among 91 Bengali individuals from Eastern India. Among them 30 individuals belong to diabetic nephropathy (DN, 30 individuals having diabetes without nephropathy (DM and 31 normal controls. The DNA samples of studied subjects were genotyped using polymerase chain reaction.Results: The frequency of DD, ID and II genotypes in patients having diabetic nephropathy (DN were found to be 26.7%, 53.3% and 20.0% respectively, whereas the same for only diabetic patients (DM were 26.7%, 50.0%and 23.3% respectively. The frequencies of the same genotypes among the normal controls were found to be 9.68%, 64.5% and 25.8% respectively. Inspite of a slightly higher odds ratio for DD genotypes among DM and DN subjects in comparison to the normal group the distribution pattern of DD genotype did not differ significantly within the three cohorts. The frequency of D allele among the patients having diabetic nephropathy, diabetic without nephropathy and control subjects was found to be 0.533, 0.516 and 0.420 respectively. This distribution pattern also did not differ significantly (χ2=1.859, p>0.05.Conclusion: No significant association was found between ACE I/D polymorphism with diabetic nephropathy patients from Bengali caste population.

  9. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Beck Stephan

    2010-08-01

    Full Text Available Abstract Background Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D. Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. Methods We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium® HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. Results Singular Value Decomposition (SVD analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. Conclusion This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy.

  10. Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease.

    Science.gov (United States)

    Savage, N W; Barnard, K; Shirlaw, P J; Rahman, D; Mistry, M; Escudier, M P; Sanderson, J D; Challacombe, S J

    2004-03-01

    Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29). Non-specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme-linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva. Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (P changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity. Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG. Serum IgA antibodies to S. cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C. albicans were elevated significantly in all three patient groups (P oral involvement. These findings suggest that raised serum IgA antibodies to S. cerevisiae may reflect gut inflammation while raised SIgA antibodies to S. cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease. Analysis of salivary IgA and IgA antibodies to S. cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement. PMID:15008983

  11. Balkan (endemic) nephropathy and foodborn ochratoxin A: preliminary results of a survey of foodstuffs.

    Science.gov (United States)

    Krogh, P; Hald, B; Plestina, R; Ceović, S

    1977-06-01

    Ochratoxin A is a nephrotoxic fungal metabolite (mycotoxin) occurring in foodstuffs. The compound is causally associated with mycotoxic porcine nephropathy, a disease comparable with a human kidney disease, Balkan endemic nephropathy. A preliminary survey of home-produced foodstuffs in areas of Yugoslavia revealed that contamination with ochratoxin A is more frequent in an area where Balkan endemic nephropathy is prevalent (endemic area) than in area where this disease is absent. This indicates higher exposure to foodborn ochratoxin A in the endemic area. Thus further evidence is provided supporting the hypothesis that ochratoxin A is a disease determinant of Balkan endemic nephropathyk0 PMID:888703

  12. Is Aristolochic Acid Really the Cause of the Balkan Endemic Nephropathy?

    Directory of Open Access Journals (Sweden)

    Peter George Mantle

    2016-03-01

    Full Text Available In recent years, aristolochic acid has been promoted vigorously as the causal agent of the Balkan endemic nephropathy because of similarities to some other nephropathies, association with DNA adducts and a perception of human exposure via bread. Critical evaluation of the literature exposes flaws in these aspects, and there has been consistent failure of experimental toxicology to mimic either the slow silent bilateral atrophy of the Balkan disease or the transitional cell carcinomas in the upper urothelium. It seems yet premature to promote the curious Balkan disease as aristolochic acid nephropathy without the epidemiological rigour necessary in biomedical research.

  13. The association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    李冬梅

    2013-01-01

    Objective To evaluate the association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients.Methods A total of 594 patients with type2 diabetes were enrolled from the inpatients of the Nanjing Medical University Affiliated Nanjing Hospital.Fasting serum lipid profile,25-hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated.The relationship between nephropathy and vitamin D deficiency (<20μg/L) or insufficiency (20-<30μg/L) was analyzed.Results Nephropathy was found in 177subjects (29.8%) with albuminuria in 141 and proteinu-

  14. Recent Advances in the Pathogenesis and Management of Cast Nephropathy (Myeloma Kidney

    Directory of Open Access Journals (Sweden)

    Stephanie Stringer

    2011-01-01

    Full Text Available Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma.

  15. Childhood proptosis

    International Nuclear Information System (INIS)

    Proptosis in children is a hallmark of orbital diseases which can present a diagnostic challenge requiring thoughtful investigation. The aim of this review is to provide the reader an overview of the subject of childhood proptosis with an emphasis on the systematic and practical approach for the work-up of proptosis in children. Use of proper imaging studies is essential for the correct diagnosis. Computed tomography is a good screening test for any space occupying lesion of the orbit. Proptosis describes eye prominence due to space occupying orbital lesions. Congenital lesions usually present in the first decade of life. Acquired orbital lesions such as lymphangiomas, orbital varix, rhabdomyosarcoma and neural tumors may present at the end of the first decade of life. Metastatic tumors to the orbit, adenocarcinoma of lacrimal gland and rapidly growing masses may present with proptosis associated with pain. Visual loss can be the presenting symptoms in the patients with optic nerve (ON) gliomas, orbital meningiomas and posteriorly located tumors. Cystic lesions of the orbit may be congenital or acquired, dermoid cysts being the most common congenital orbital lesions. Some of the vascular lesions of the orbit include capillary hemangiomas, lymphangiomas, orbital varix, and arteriovenous malformations. Inflammatory process of the orbit in children include cellulitis and pseudotumor. Neural tumors such as neurofibromas, ON gilomas and meningiomas are less common causes of proptosis in children. Rhabdomyosarcoma is the most common primary orbital malignancy in children which can present with acute proptosis and is one of the few life-threatening diseases seen initially by an ophthalmologist. Secondary orbital tumors invade the orbit from adjacent sinuses, cranium or extended from the eye itself. The most common distant metastases in children include neuroblastoma and Ewing's sarcoma. Although many orbital processes can be diagnosed based on history, clinical

  16. Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy

    Directory of Open Access Journals (Sweden)

    Pengxun Han

    2013-09-01

    Full Text Available Aims: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. Methods: Adriamycin nephropathy was induced in male Wistar rats (n=12 by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. Results: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. Conclusions: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.

  17. Iga neljas kontrollitud noorsõdur tuli püssi alla narkopohmellis / Rasmus Kagge, Dagne Hanschmidt

    Index Scriptorium Estoniae

    Kagge, Rasmus, 1977-

    2008-01-01

    Ilmunud ka: Postimees : na russkom jazõke 2. okt. lk. 5. Politsei korraldatud reidil Kuperjanovi üksik-jalaväepataljoni saabunud uutel ajateenijatel tuvastati, et iga neljas noorsõdur oli tarvitanud narkootikume. Vt. samas: Ajateenijad

  18. Alterations of urinary metabolite profile in model diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  19. Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA.

    Directory of Open Access Journals (Sweden)

    Cristina Antonella Nadalutti

    Full Text Available PURPOSE: To investigate the role of thioredoxin (TRX, a novel regulator of extracellular transglutaminase 2 (TG2, in celiac patients IgA (CD IgA mediated TG2 enzymatic activation. METHODS: TG2 enzymatic activity was evaluated in endothelial cells (HUVECs under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study. RESULTS: We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity. CONCLUSIONS: Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX.

  20. Immunohistochemical study of in vivo and in vitro IgA coating of candida species in vulvovaginal candidiasis.

    OpenAIRE

    Böhler, K; Klade, H; Poitschek, C; Reinthaller, A.

    1994-01-01

    OBJECTIVE--To evaluate whether quantitative or qualitative IgA deficiencies in cervicovaginal secretions can be identified in patients with recurrent vulvovaginal candidiasis. DESIGN--Prospective and controlled study. SETTING--Department of Dermatology, University of Vienna. SUBJECTS--30 patients with symptomatic and recurrent vulvovaginal candidiasis at the time of their presentation. 30 healthy women as a control group. INTERVENTION--Blood samples were drawn for measurement of serum IgA lev...

  1. Development of intestinal mucin 2, IgA, and polymeric Ig receptor expressions in broiler chickens and Pekin ducks.

    Science.gov (United States)

    Zhang, Qian; Eicher, Susan D; Applegate, Todd J

    2015-02-01

    Intestinal mucin 2 (MUC2), a major gel-forming mucin, represents a primary barrier component of mucus layers and a target site for secretory IgA. Polymeric Ig receptor (pIgR) expressed on the basolateral surface of epithelium is used to transport polymeric IgA from the lamina propria into luminal mucins to establish the first lines of intestinal defense. To determine the spatio-temporal expression of MUC2, IgA, and pIgR in broiler chickens and Pekin ducks, intestinal tissues (n=6/age) were dissected from late embryonic days up to 21 d posthatch. In the intestinal tissues, MUC2 was expressed with a rapid increase at hatching, followed by steady expression through 21 d posthatch both in chickens and ducks. IgA expression was low during the first week following hatching for both species. From the second week posthatch, IgA was rapidly expressed in the chickens, arriving at steady expression in the third week after hatching. However, in ducks, IgA expression during the 2 to 3 wk posthatch period was relatively slow. The expression of pIgR was greatly increased after hatching for both species, but its expression in ducks was relatively delayed. In addition, intestinal pIgR expression was highly correlated with MUC2 and IgA expressions in chickens but just moderately correlated in ducks. The relatively slow and late expression of IgA and pIgR as well as their moderate correlation may or may not account for the susceptibility of ducklings to mucosal pathogens at a young age. PMID:25589081

  2. Human Leukocyte Antigens (HLA Associated with Selective IgA Deficiency in Iran and Sweden

    Directory of Open Access Journals (Sweden)

    Mohammadi Javad

    2008-12-01

    Full Text Available Selective IgA deficiency (IgAD (serum IgA concentration of PCR was used to type HLA B, DR, and DQ alleles in 29 Iranian individuals with IgAD and 299 Swedish individuals with IgAD. The results indicate a strong association with the HLA B14, DR1 alleles in Iranian subjects and HLA B8, B12, B13, B14, B40, DR1, DR3, DR7, DQ2 and DQ5 alleles in Swedish subjects.Differences in HLA association of IgAD in Iran and Sweden confirm the notion of a genetic background of the disease and that multiple, potentially different genes within the MHC region might be involved in the pathogenesis of IgAD in different ethnic groups.

  3. Human leukocyte antigens (HLA) associated with selective IgA deficiency in Iran and Sweden.

    Science.gov (United States)

    Mohammadi, Javad; Pourpak, Zahra; Jarefors, Sara; Saghafi, Shiva; Zendehdel, Kazem; Pourfathollah, Ali Akbar; Amirzargar, Ali Akbar; Aghamohammadi, Asghar; Moin, Mostafa; Hammarstrom, Lennart

    2008-12-01

    Selective IgA deficiency (IgAD) (serum IgA concentration of HLA-A1, B8, DR3, DQ2) have previously been shown to be increased among Caucasian patients with IgAD.PCR was used to type HLA B, DR, and DQ alleles in 29 Iranian individuals with IgAD and 299 Swedish individuals with IgAD.The results indicate a strong association with the HLA B14, DR1 alleles in Iranian subjects and HLA B8, B12, B13, B14, B40, DR1, DR3, DR7, DQ2 and DQ5 alleles in Swedish subjects.Differences in HLA association of IgAD in Iran and Sweden confirm the notion of a genetic background of the disease and that multiple, potentially different genes within the MHC region might be involved in the pathogenesis of IgAD in different ethnic groups. PMID:19052350

  4. Physical exercise, salivary IgA and mood states of elderly people

    Directory of Open Access Journals (Sweden)

    R. Martins

    2008-01-01

    Full Text Available It is generally accepted that the aging process is associated with immunosenescence. On the other hand, physical activity has been consistently associated with positive states of affection and mood which also implies gains on psychological well-being. However, more studies are needed to support the benefit effect of exercise on specific population groups like the elderly. The purpose of the present work is to study the functional fitness, mood states and salivary IgA chronic adaptations after a physical exercise program. 28 subjects aged between 65 and 95 years old participated in this study. The experimental group exercised during 16 weeks, 3 times per week. The Wilcoxon test was used to compare the data. The results showed positive changes on the functional fitness that reinforce the trainability principle of the older person. The data shows also an improvement in mood states and chronic positive effects on salivary IgA after the exercise program.

  5. Generalized Shape and Gauge Decoupling Load Distribution Optimization Based on IGA for Tandem Cold Mill

    Institute of Scientific and Technical Information of China (English)

    PENG Peng; YANG Quan

    2009-01-01

    Load distribution is the foundation of shape control and gauge control, in which it is necessary to take into account the shape control ability of TCM (tandem cold mill) for strip shape and gauge quality. First, the objective function of generalized shape and gauge decoupling load distribution optimization was established, which considered the rolling force characteristics of the first and last stands in TCM, the relative power, and the TCM shape control ability. Then, IGA (immune genetic algorithm) was used to accomplish this multi-objective load distribution optimization for TCM. After simulation and comparison with the practical load distribution strategy in one tandem cold mill, general-ized shape and gauge decoupling load distribution optimization on the basis of IGA approved good ability of optimizing shape control and gauge control simultaneously.

  6. Incidence of Contrast-Induced Nephropathy after Contrast-Enhanced Computed Tomography in the Outpatient Setting

    OpenAIRE

    Mitchell, Alice M.; Jones, Alan E.; James A Tumlin; Kline, Jeffrey A.

    2010-01-01

    Background and objectives: No prospective study has reported the incidence of contrast-induced nephropathy (CIN) or the associated morbidity and mortality after contrast-enhanced computed tomography (CECT) in the outpatient setting.

  7. Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.

    LENUS (Irish Health Repository)

    Johnston, Olwyn

    2011-08-01

    Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals.

  8. Linear IgA dermatosis adult variant with oral manifestation: A rare case report

    Directory of Open Access Journals (Sweden)

    T Isaac Joseph

    2015-01-01

    Full Text Available Linear immunoglobulin A (IgA dermatosis (LAD is a rare autoimmune disorder that presents as a vesiculo-bullous lesion with cutaneous manifestations, but rare oral mucosal involvement. Here we discuss a case of a vesiculobullous lesion with severe oral and ocular mucosal involvement mimicking pemphigoid with histopathological evidence of subepithelial blisters. Direct immunofluorescence (DIF confirmed the lesion as LAD of adult variant, although with atypical clinical features.

  9. Salivary IgA and periodontal treatment needs in diabetic patients

    OpenAIRE

    Luciana Salles Branco-de-Almeida; Cláudia Maria Coêlho Alves; Fernanda Ferreira Lopes; Adriana de Fátima Vasconcelos Pereira; Rosane Nassar Meireles Guerra; Antônio Luiz Amaral Pereira

    2011-01-01

    Salivary IgA can serve as a first line of defense against pathogens that colonize and invade mucosal surfaces and may be protective against periodontal disease. The aim of this study was to assess salivary immunoglobulin A levels in diabetic and non-diabetic patients with different periodontal treatment needs. The Periodontal Screening & Recording (PSR) system was used to evaluate the periodontal treatment needs of 41 diabetic and 42 non-diabetic patients. Unstimulated whole saliva was collec...

  10. IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production

    OpenAIRE

    Jung, Y.; T. Wen; Mingler, MK; Caldwell, JM; Wang, YH; Chaplin, DD; Lee, EH; Jang, MH; Woo, SY; Seoh, JY; Miyasaka, M; Rothenberg, ME

    2015-01-01

    Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double–deficient or CC chemokine receptor 3–deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial compositi...

  11. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

    Directory of Open Access Journals (Sweden)

    S. A. Donina

    2008-01-01

    Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.

  12. A comparison of salivary IgA in children with Down syndrome and their family members.

    Science.gov (United States)

    Balaji, Karthika; Milne, Trudy J; Drummond, Bernadette K; Cullinan, Mary P; Coates, Dawn E

    2016-07-01

    The aim of this study was to compare total IgA in the whole saliva of children with Down syndrome with levels in sibling and parent groups. IgA measurements were presented as the concentration in saliva (μg/ml) and also adjusted for salivary flow rate (SFR; μg/min). Twenty children with Down syndrome, ten siblings and twenty parents were recruited. Stimulated whole saliva was collected from the participants and SFR calculated. The measurement of salivary IgA (sIgA) was carried out using an indirect competitive Enzyme-Linked Immunosorbent Assay. The difference in the mean SFR between children with Down syndrome, parents and siblings were not statistically significant. The mean salivary concentration of IgA was higher in children with Down syndrome (95.1μg/ml) compared with siblings (48.3μg/ml; p=0.004). When adjusted for SFR children with Down syndrome had mean sIgA levels of 98.8μg/min and the siblings 48.6μg/min (p=0.008). The children with Down syndrome had sIgA levels similar to those of the parents (92.5μg/ml; 93.2μg/min). There was a positive correlation between age and sIgA concentration in the siblings (p=0.008) but not for children with Down syndrome (p=0.363). This suggests that under similar environmental influences, the levels of sIgA in children with Down syndrome are higher than in the siblings, from a very young age. PMID:27023400

  13. Identification of residues in the CH2/CH3 domain interface of IgA essential for interaction with the human fcalpha receptor (FcalphaR) CD89.

    Science.gov (United States)

    Pleass, R J; Dunlop, J I; Anderson, C M; Woof, J M

    1999-08-13

    Cellular receptors for IgA (FcalphaR) mediate important protective functions. An extensive panel of site-directed mutant IgAs was used to identify IgA residues critical for FcalphaR (CD89) binding and triggering. Although a tailpiece-deleted IgA1 was able to bind and trigger CD89, antibodies featuring CH3 domain exchanges between human IgA1 and IgG1 could not, indicating that both domains but not the tailpiece are required for FcalphaR recognition. To further investigate the role of the interdomain region, numerous IgA1s, each with a point substitution in either of two interdomain loops (Leu-257-Gly-259 in Calpha2; Pro-440-Phe-443 in Calpha3), were generated. With only one exception (G259R), substitutions produced either ablation (L257R, P440A, A442R, F443R) or marked reduction (P440R) in CD89 binding and triggering. Further support for involvement of these interdomain loops was provided by interspecies comparisons of IgA. Thus a human IgA1 mutant, LA441-442MN, which mimicked the mouse IgA loop sequence through substitution of two adjacent residues in the Calpha3 loop, was found, like mouse IgA, not to bind CD89. In contrast, bovine IgA1, identical to human IgA1 within these interdomain loops despite numerous differences elsewhere in the Fc region, did bind CD89. We have thus identified motifs in the interdomain region of IgA Fc critical for FcalphaR binding and triggering, significantly enhancing present understanding of the molecular basis of the IgA-FcalphaR interaction. PMID:10438530

  14. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    NARCIS (Netherlands)

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Cahn, W

    2015-01-01

    BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect

  15. Bestimmung der Albuminausscheidung im Urin bei Diabetikern zur Vorsorge und Kontrolle der diabetischen Nephropathie

    OpenAIRE

    Schroeder, A.; Heiderhoff, M; KÖBBERLING, J.

    2005-01-01

    The issue Diabetes has become the main cause of endstage renal disease. The costs for the treatment of diabetic patients with endstage renal disease have increased in the last years and have become a relevant economic topic of the health service. The first unspecific predictor of a diabetic nephropathy is an albuminuria. The screening for diabetic nephropathy uses microalbuminuria as a proof. Objectives What significance does the determination of albuminuria have on the precaution and course...

  16. The Role of Bone Marrow Cells in the Phenotypic Changes Associated with Diabetic Nephropathy

    OpenAIRE

    Guang Yang; Qingli Cheng; Sheng Liu; Jiahui Zhao

    2015-01-01

    The aim of our study was to investigate the role of bone marrow cells in the phenotypic changes that occur in diabetic nephropathy. Bone marrow cells were obtained from either streptozotocin-induced diabetic or untreated control C3H/He mice and transplanted into control C3H/He mice. Eight weeks after bone marrow cell transplantation, renal morphologic changes and clinical parameters of diabetic nephropathy, including the urine albumin/creatinine ratio and glucose tolerance, were measured in v...

  17. Membranous nephropathy with repeated flares in IgG4-related disease

    OpenAIRE

    Kanda, Hiroko; Koya, Junji; Uozaki, Hiroshi; Tateishi, Shoko; Sato, Kojiro; Hagino, Noboru; Sawada, Tetsuji; Yamamoto, Kazuhiko

    2013-01-01

    IgG4-related disease (IgG4-RD) is associated with the infiltration of IgG4-positive plasma cells into various organs. Nephropathy of IgG4-RD is generally interstitial nephritis and glomerulonephritis is rare. We describe a case of membranous nephropathy (MN) without interstitial nephritis associated with IgG4-RD symptoms including lymphadenopathy and pulmonary and pleural lesions. Treatment with steroids improved these clinical symptoms, but withdrawal of steroids induced the repeated relapse...

  18. Membranous nephropathy as a rare renal manifestation of IgG4-related disease

    OpenAIRE

    Kurien, A. A.; RayChaudhury, A; Walker, P D

    2015-01-01

    IgG4-related disease, a newly described immune-mediated disorder with tissue infiltration of IgG4-positive plasma cells, has been reported in nearly every organ. In the kidney, it manifests as IgG4-related tubulointerstitial nephritis (TIN) but may also present as membranous nephropathy. We report a patient with IgG4 renal disease who had membranous nephropathy as well as TIN.

  19. Determination of albuminuria in the urine of diabetics for prevention and control of diabetic nephropathy

    OpenAIRE

    Köbberling, Johannes; Schroeder, Andreas; Heiderhoff, Marc

    2005-01-01

    The issue: Diabetes has become the main cause of endstage renal disease. The costs for the treatment of diabetic patients with endstage renal disease have increased in the last years and have become a relevant economic topic of the health service. The first unspecific predictor of a diabetic nephropathy is an albuminuria. The screening for diabetic nephropathy uses microalbuminuria as a proof. Objectives: * What significance does the determination of albuminuria have on the precaution and cou...

  20. Diabetic Nephropathy and Microalbuminuria in Pregnant Women With Type 1 and Type 2 Diabetes

    OpenAIRE

    Damm, Julie Agner; Ásbjörnsdóttir, Björg; Callesen, Nicoline Foged; Mathiesen, Jonathan M.; Ringholm, Lene; Pedersen, Berit Woetmann; Mathiesen, Elisabeth R

    2013-01-01

    OBJECTIVE To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol. RESEARCH DESIGN AND METHODS Among 220 women with type 2 diabetes and 445 women with type 1 diabetes giving birth from 2007–2012, 41 women had diabetic nephropathy (albumin-creatinine ratio ≥300 mg/g) or microalbuminuria (albumin-creatinine ratio...

  1. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.;

    2009-01-01

    Patients with diabetes mellitus (DM) have increased platelet activation compared to non-diabetic controls. Platelet hyperreactivity has been associated with adverse cardiovascular outcomes in Type 2 DM, and with diabetic nephropathy. We investigated the relationship between platelet activation and...... with normoalbuminuria, is associated with circulating activated platelets and platelet hyperreactivity to ADP, despite the confounding variable of more nephropathy patients receiving aspirin. This platelet activation is likely to contribute to the known increased risk of cardiovascular events in...

  2. Diabetic Nephropathy and Microalbuminuria in Pregnant Women With Type 1 and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Damm, Julie Agner; Asbjörnsdóttir, Björg; Callesen, Nicoline Foged; Mathiesen, Jonathan Michael; Ringholm, Lene; Pedersen, Berit Woetmann; Mathiesen, Elisabeth R

    2013-01-01

    To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol.......To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol....

  3. Effect of Eugenia Jambolana on Streptozotocin-Nicotinamide induced type-2 Diabetic Nephropathy in Rats

    OpenAIRE

    Godwin Selvaraj Esther; Alvin Jose Manonmani

    2014-01-01

    The chronic type-2 diabetes mellitus leads to diabetic nephropathy, which is one of the major microvascular complication of end stage renal disease worldwide and causes premature death in diabetic patients. The objective of the present investigation was to evaluate the antidiabetic activity and protective effect of diabetic induced nephropathy of ethanolic extract of seeds of Eugenia jambolana (SEEJ) by using in-vitro and in-vivo models. The in-vitro antidiabetic effect was studied by glucose...

  4. Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy.

    OpenAIRE

    Bakhiya, Nadiya; Arlt, Volker M.; Bahn, Andrew; Burckhardt, Gerhard; Phillips, David H.; Glatt, Hansruedi

    2009-01-01

    Aristolochic acid (AA), present in Aristolochia species, is the major causative agent in the development of severe renal failure and urothelial cancers in patients with AA nephropathy. It may also be a cause of Balkan endemic nephropathy. Epithelial cells of the proximal tubule are the primary cellular target of AA. To study whether organic anion transporters (OATs) expressed in proximal tubule cells are involved in uptake of AA, we used human epithelial kidney (HEK293) cells stably expressin...

  5. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

    OpenAIRE

    Jang Hyun Koh; Eun Soo Lee; Miri Hyun; Hong Min Kim; Yoon Jung Choi; Eun Young Lee; Dhananjay Yadav; Choon Hee Chung

    2014-01-01

    The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n = 10), OLETF rats as diabetic control group (n = 10), and OLETF rats treated with taurine group (n = 10). We treated taurine (200 mg/kg/day) for 20 weeks ...

  6. Urinary sulphate excretion and progression of diabetic nephropathy in Type 1 diabetes

    DEFF Research Database (Denmark)

    Andrésdóttir, G; Bakker, S J L; Hansen, H P; Parving, H-H; Rossing, P

    2013-01-01

    Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy.......Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy....

  7. Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review

    OpenAIRE

    Lei Zhang; Wei Mao; Xinfeng Guo; Yifan Wu; Chuang Li; Zhaoyu Lu; Guobin Su; Xiaoyan Li; Zhuangzhu Liu; Rong Guo; Xina Jie; Zehuai Wen; Xusheng Liu

    2013-01-01

    Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Dat...

  8. An unusual presentation of venous thrombosis in a child with idiopathic membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Sreekanth Burri

    2015-01-01

    Full Text Available Venous thrombosis is one of the major complications associated with nephrotic syndrome. Among the primary glomerular diseases, membranous nephropathy is associated with a high incidence of thrombotic events. Although this is well described in adults, there is paucity of the literature regarding venous thrombosis in children. Herein, we report such a thrombotic event involving both the lower limb veins and the inferior vena cava in a child with membranous nephropathy.

  9. Urinary proteomics for early diagnosis in diabetic nephropathy

    DEFF Research Database (Denmark)

    Zürbig, Petra; Jerums, George; Hovind, Peter; Macisaac, Richard J; Mischak, Harald; Nielsen, Stine; Panagiotopoulos, Sianna; Persson, Frederik; Rossing, Peter

    2012-01-01

    Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing...... diabetic patients (n = 35) using a previously generated chronic kidney disease (CKD) biomarker classifier to assess peptides of collected urines for signs of DN. The application of this classifier to samples of normoalbuminuric subjects up to 5 years prior to development of macroalbuminuria enabled early...... detection of subsequent progression to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary albuminroutinely used to determine the diagnosis (AUC 0.67). Statistical analysis of each urinary CKD biomarker depicted its regulation with respect to diagnosis of DN over time. Collagen...

  10. Contrast-induced nephropathy: The wheel has turned 360 degrees

    DEFF Research Database (Denmark)

    Thomsen, H.S.; Morcos, S.K.; Barrett, B.J.;

    2008-01-01

    publications under the heading CIN have been published during the last 5 years. Fewer than 5% of these publications are randomized prospective controlled studies. In spite of the large number of reports on CIN, very little has been changed. The use of the smallest possible dose of low- or iso-osmolar contrast......Contrast-induced nephropathy (CIN) has been a hot topic during the last 5 years due its association with increased morbidity and mortality. CIN is an important complication, particularly in patients with advanced chronic kidney disease (CKD) associated with diabetes mellitus. Methods to diminish...... the incidence of CIN have been highly contentious. They include choice of contrast, pharmacologic manipulation, and volume expansion. The pathophysiology of this complication remains uncertain, but reduction in renal blood flow and direct toxicity of tubular cells has been implicated. More than 900...

  11. Changes and role of adrenomedullin in diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Huimin Li; Heng Miao; Xiuqin Jian; Fageng Hou

    2005-01-01

    Objective: To investigate the role and mechanism of adrenomedullin (AM) in diabetic nephropathy. Methods:This research observed the changes of the expression and secretion of AM, TGF-β1 in the cultured human mesangial cells under high glucose conditions and the contents of the laminin and type Ⅳ collagen in the supernatants, and the effect of intervention with AM on the changes.Results: High glucose condition resulted in increase in the expression and secretion of AM, TGF-β1, laminin and type Ⅳ collagen, and AM could reverse the influence of high glucose on the cultured human mesangial cells. Conclusion: The results showed that high glucose condition in one of the stimulating factors of AM, and the renal protective action of AM may be associated with suppression of TGF-β1 and reducing excessive accumulation of laminin and type Ⅳ collagen.

  12. A Case of Acute Phosphate Nephropathy After Colonoscopy

    Directory of Open Access Journals (Sweden)

    Ömer Celal ELÇİOĞLU

    2013-01-01

    Full Text Available Acute phosphate nephropathy is a form of acute kidney injury (AKI due to oral sodium phosphate (ONaP purgatives used for bowel cleansing before colonoscopy. Usually, 45 ml ONaP is given two times daily 12-24 hours prior to colonoscopy. Intestinal absorption is followed by transient hypocalcemia and hyperphosphatemia in almost all patients. In addition, severe hyperphosphatemia, symptomatic hypocalcemia, hypernatremia, hypocalcemia, hyponatremia, hypokalemia, high anion gap metabolic acidosis and AKI can be seen. The patient presented in this paper is a 65-year-old female. She was diagnosed with type 2 diabetes mellitus and hypertension. Colonoscopy was performed in order to investigate the etiology of iron deficiency anemia. ONaP was administered for preparation of colonoscopy and AKI which was clinically compatible with APN developed after the procedure.

  13. Membranous nephropathy in the cat: a clinical and pathological study.

    Science.gov (United States)

    Nash, A S; Wright, N G; Spencer, A J; Thompson, H; Fisher, E W

    1979-07-28

    A series of 13 cases of feline membranous nephropathy is presented. Two groups were distinguished clinically; eight cats had the nephrotic syndrome and five others were in renal failure but not nephrotic. The definitive diagnosis was based on histological, immunofluorescence and ultrastructural examinations of renal tissue obtained at renal biopsy or necropsy. Glomerular lesions were classified according to the degree of glomerular change into three distinct groups; mild, moderately severe and advanced. A relationship was established between the mild and moderately severe groups and cats with the nephrotic syndrome, and the advanced group and cats in renal failure. Diuretic therapy was satisfactory in initial control of oedema in the nephrotic cases. Monitoring of previously nephrotic cats for up to three years indicated that the disease is progressive, although in some cases it is sufficiently slow for a cat to live a relatively normal life without continuing treatment. The prognosis for cats presented in renal failure is hopeless. PMID:552741

  14. Neuropathies associated with IgG and IgA monoclonal gammopathy.

    Science.gov (United States)

    Nobile-Orazio, E; Casellato, C; Di Troia, A

    2002-10-01

    Neuropathy has been frequently reported in patients with monoclonal gammopathy, particularly those with monoclonal gammopathy of undetermined significance (MGUS). While the neuropathy associated with IgM-MGUS is well characterized and is often associated with a reactivity of the monoclonal protein with neural antigens, the relationship between the neuropathy and IgG and IgA MGUS is less clear. We review here the clinical, electrophysiological and pathogenetic features of neuropathies associated with IgG and IgA M-proteins in order to determine whether they represent distinct clinical entities and, most importantly, whether the finding of an IgG or IgA monoclonal gammopathy in a patient with neuropathy should led to different diagnostic or therapeutical approaches. This review will mainly focus on neuropathies associated with MGUS since the disclosure of a malignant monoclonal gammopathy, including multiple or osteosclerotic myeloma, lymphoma or primary amyloidosis, in a patient with neuropathy usually divert the therapeutical decisions to the hematologist for an appropriate therapy of the underlying life threatening condition. PMID:12407307

  15. Detection of secretory IgM in tears of IgA deficient individuals.

    Science.gov (United States)

    Kuizenga, A; Stolwijk, T R; van Agtmaal, E J; van Haeringen, N J; Kijlstra, A

    1990-10-01

    Tears from normal (n = 5) and serum IgA deficient (n = 3) individuals were investigated for the presence of secretory Immunoglobulin A (sIgA), sIgM and free secretory component (SC) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) using 10-15% gradient minigels (PhastSystem), followed by immunoblotting using various immunological probes. Tear samples were treated in denaturing (SDS) sample buffer under non-reducing as well as reducing conditions, prior to analysis. All normal tear samples contained sIgA as well as free SC (estimated MW: 82kD) but only traces of IgM. Tears from the three serum IgA deficient subjects lacked sIgA but did contain free SC. In two of them sIgM was clearly detected and after treatment of tears with reducing agent, IgM (mu) heavy chain fragments (estimated MW: 78kD) were identified and could be distinguished from other tear proteins after SDS-PAGE. These findings indicate lacrimal secretion of free secretory component, even in the absence of its ligand. On the ocular surface, sIgM may play a compensatory role in IgA deficiency. PMID:2125905

  16. Reducing the Risks for Contrast-Induced Nephropathy

    International Nuclear Information System (INIS)

    Contrast-induced nephropathy (CIN) is one of the most serious adverse events associated with the use of contrast media (CM). Patients who develop this complication can have increased morbidity, higher rates of mortality, lengthy hospital stays, and poor long-term outcomes. Although CIN cannot be eliminated, the chances of developing this condition can be reduced by using appropriate prevention strategies. An important first step to reduce the chance of CIN is to identify risk factors associated with this condition. Patients with a previously elevated serum creatinine level, especially when secondary to diabetic nephropathy, are at great risk for developing CIN. Other patient-related risk factors include concurrent use of nephrotoxic medications, dehydration, congestive heart failure, age greater than 70 years, and probably the presence of diabetes mellitus even if serum creatinine is normal. Adequate hydration is widely accepted as an important prophylactic measure for preventing CIN, but the optimal hydration regimen is still debatable. The risk of CIN increases with greater doses of CM, as well as with the type of CM used. A high-osmolar CM poses a greater risk of CIN than does a low-osmolar CM and, as recent but limited data suggest, the use of an iso-osmolar CM is less nephrotoxic than a low-osmolar CM in patients with renal impairment following intra-arterial procedures, although this finding needs to be verified in future clinical studies. Pharmacologic agents such as calcium channel blockers, dopamine, atrial natriuretic peptide, fenoldopam, prostaglandin E1, and endothelin receptor antagonist have not been proven effective against CIN development. Controversies still exist on the possible effectiveness of theophylline and N-acetylcysteine. Simple strategies for the prevention of CIN in at-risk patients are reviewed and unproven interventions are discussed

  17. Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia.

    Science.gov (United States)

    Heyman, S N; Reichman, J; Brezis, M

    1999-11-01

    Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease. PMID:10548380

  18. Effect of atorvastatin on preventing contrast-induced nephropathy

    International Nuclear Information System (INIS)

    Objective: To study the effects of atorvastatin on contrast-induced renal function and urinary protein change in patients undergoing diagnostic and therapeutic coronary intervention. Methods: Two hundred and forty-six patients who underwent coronary angiography or percutaneous coronary intervention (PCI) were randomized to receive atorvastatin (40 mg, qn, n=123) or no atorvastatin (n=123) treatment 3 days before coronary angiography. All patients received hydrated therapy. Serum creatinine (Scr), urinary αl-microglobulin (αl-MG), and urinary albumin (mALB) were checked for evidence of tubular or glomerular damage at start, and 36 to 48 hours after the administration of a radiocontrast agent. High-sensitive C-reactive protein (hsCRP) levels, urinary αl-MG/ urinary creatinine(Ucr) and mALB/ Ucr were also assessed at the same time. Creatinine clearance(Ccr) was calculated according to Cockcroft-Gault formulas basing on serum creatinine. Results: (1) In the control group and atorvastatin-treated group, comparison with the value before coronary angiography or PCI, urinary αl-MG/ Ucr, mALB/ Ucr, Scr and hsCRP significantly increased from 36 to 48 hours after angiography or PCI (Pl-MG/ Ucr significantly increased at the 2nd day after angiography or PCI in the control group (P<0.05), incidence of contrast induced nephropathy (CIN) significantly increased too (8.13% vs 0.81%, P<0.05). Conclusions: Contrast media induces light renal function damage. Pretreatment with atorvastatin 40 mg/qn for 3 days could significantly reduce procedural inflammatory reaction and prevent contrast-induced nephropathy. (authors)

  19. Dietary hypercholesterolemia aggravates contrast media-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨定位; 贾汝汉; 杨定平; 丁国华; 黄从新

    2004-01-01

    Background Contrast media administration can result in severe nephrotoxicity under pathological conditions such as diabetic nephropathy, congestive heart failure, dehydration, et al. The purpose of this study was to evaluate the effects of dietary hypercholesterolemia on contrast media-induced changes in renal function, blood flow, and histopathology.Methods Rats were fed either on a normal rodent diet (group N) or a high-cholesterol supplemented diet (group H; 4% cholesterol and 1% cholic acid) for 8 weeks. Half of the animals (n =6) from each diet group were then given a tail vein injection of 60% diatrizoate (6 ml/kg; group NC and group HC)and the other half were administered saline. Total serum cholesterol, triglyceride, serum creatinine,creatinine clearance rate, fractional excretion of sodium and potassium, and cortical nitric oxide production were determined one day following contrast media administration. Renal blood flow was determined by color Doppler flow imaging and pulsed-mode Doppler. Renal histopathology was observed by light microscopy.Results Total serum cholesterol and resistance indices of renal blood vessels increased significantly,while creatinine clearance rate and production of nitric oxide in the renal cortex decreased markedly in group HC and group H when compared to group N and group NC. The creatinine clearance rate decreased significantly in group HC compared to group H. Serum creatinine levels and fractional excretion of sodium and potassium in group HC were significantly higher than those in the other three groups. Severe tubular degeneration and necrosis, protein cast accumulation, and medullary congestion were found in group HC.Conclusion Hypercholesterolemia is a risk factor for contrast media-induced nephropathy.Hypercholesterolemia aggravates contrast media-induced nephrotoxicity through the reduced production of nitric oxide.

  20. Changes of plasma levels of homocysteine (Hcy) and urinary albumin contents in patients with type 2 diabetes complicated with nephropathy

    International Nuclear Information System (INIS)

    Objective: To study the changes of plasma levels of homocysteine (Hcy) and urinary albumin contents in patients with type 2 diabetes complicated with nephropathy. Methods: Plasma Hcy (with fluorescence immunoassay) fasting glucose, BUN, Cr (with biochemistry) levels and urinary albumin contents (with RIA) were determined in 36 DM2 patients without nephropathy, 30 DM2 patients with nephropathy and 30 controls. Results: The fasting blood glucose levels in the 2 groups of diabetic patients were not much different. Again, the BUN and Cr levels in the 3 groups of patients were about the same. The plasma Hcy levels in the group of patients with diabetic nephropathy were significantly higher than those in both controls and DM2 patients without nephropathy (all P<0.01). Conclusion: Hyperhomocysteinemia is a risk factor for nephropathy in DM2 patients. (authors)

  1. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    International Nuclear Information System (INIS)

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs

  2. Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Shinji Kume

    2014-01-01

    Full Text Available Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.

  3. Childhood as a value

    OpenAIRE

    EWELINA PIECUCH

    2011-01-01

    The article encompasses the problems of childhood and its influence on the rest of one's life. I have concentrated on this crucial and specific time in life. It is demonstrated by biology, medicine, psychology, and psychoanalysis that human habits are formed in childhood. Health, hygiene and aesthetic behaviour determine one's further fate and influence life in its entirety. It is that phase of human life that determines the rest of it. In childhood children manifest their cogn...

  4. Childhood Cancer Survivor Study: An Overview

    Science.gov (United States)

    ... Cancers of Childhood Treatment Childhood Cancer Genomics Research Childhood Cancer Survivor Study: An Overview In 2016, it ... Late Effects of Treatment for Childhood Cancer .) The Childhood Cancer Survivor Study ( CCSS ), funded by the National ...

  5. Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy.

    Science.gov (United States)

    Oltean, Sebastian; Qiu, Yan; Ferguson, Joanne K; Stevens, Megan; Neal, Chris; Russell, Amy; Kaura, Amit; Arkill, Kenton P; Harris, Kirstie; Symonds, Clare; Lacey, Katja; Wijeyaratne, Lihini; Gammons, Melissa; Wylie, Emma; Hulse, Richard P; Alsop, Chloe; Cope, George; Damodaran, Gopinath; Betteridge, Kai B; Ramnath, Raina; Satchell, Simon C; Foster, Rebecca R; Ballmer-Hofer, Kurt; Donaldson, Lucy F; Barratt, Jonathan; Baelde, Hans J; Harper, Steven J; Bates, David O; Salmon, Andrew H J

    2015-08-01

    Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy. PMID:25542969

  6. Kidney biopsy

    Science.gov (United States)

    ... Goodpasture syndrome IgA nephropathy Interstitial nephritis Lupus nephritis Medullary cystic kidney disease Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease Nephrotic ...

  7. SERUM IgA LEVELS IN SCHOOL GOING CHILDREN IS INDEPENDENT OF NUTRITIONAL STATUS AND MORBIDITY Profile- a Cross Sectional Study of Urban Vadodara

    OpenAIRE

    Tanu Shree Singh; Mini Sheth

    2014-01-01

    IgA levels are considered as one of the most important determinant of immunity in children and undernutrition may result in deviated IgA levels due to repetitive infection resulting in acute respiratory infections (ARI) and diarrhoea. Hence, the study was undertaken to determine serum IgA levels of 80 undernourished and 30 nourished children using Immunoturbidimetric assay and correlate with their nutritional and morbidity status. Due to the known variability of immunoglobulin levels, subject...

  8. Renal Transplantation Dramatically Reduces IgA Anti-beta-2-glycoprotein I Antibodies in Patients with Endstage Renal Disease

    Directory of Open Access Journals (Sweden)

    Manuel Serrano

    2014-01-01

    Full Text Available IgA anti-beta-2-glycoprotein I (aB2GPI antibodies have been related to vascular pathology in the general population and mainly in hemodialyzed patients (prevalence 33% in whom an elevated incidence of thrombosis and mortality is found. In this paper we have studied the presence of IgA aB2GPI antibodies at pretransplant and their evolution after transplantation with a cross-sectional-based follow-up study of a cohort of 288 endstage renal disease (ESRD patients treated with kidney transplantation. Pretransplant IgA aB2GPI levels were elevated 31.7±4.2 U/mL without differences in age or type of dialysis. Patients with different etiologies of ESRD showed higher levels of IgA aB2GPI than blood donors, except the groups of non-IgA glomerular disease and systemic erythematosus lupus, whose nonsignificant differences were observed. IgA aB2GPI antibodies dropped immediately after transplantation (10.7±1.0 U/mL, P<0.0001, coinciding with a high degree of immunosuppression, and remained significantly lower than that observed in pretransplant status. Prevalence of patients with elevated antibodies was also less in transplanted patients (8.9% versus 30.4%, P<0.0001. Among, positivity for IgA aB2GPI was higher than in patients who had received their first transplant that those were retransplanted. This finding could have important clinical implications and can suggest new therapeutic strategies in patients with IgA aB2GPI antibodies.

  9. Similarity of fine specificity of IgA anti-gliadin antibodies between patients with celiac disease and humanized α1KI mice.

    Science.gov (United States)

    Sánchez, Daniel; Champier, Gaël; Cuvillier, Armelle; Cogné, Michel; Pekáriková, Aneta; Tlaskalová-Hogenová, Helena; Hoffmanová, Iva; Drastich, Pavel; Mothes, Thomas; Tučková, Ludmila

    2011-04-13

    Gliadins, and primarily α-gliadins containing several sequences such as aa 31-49, aa 56-88 (33-mer), aa 57-68, and aa 69-82, are critical in the induction of immune response or toxic reaction leading to the development of celiac disease (CLD). The role of IgA anti-gliadin antibodies (IgA AGA) is unknown. To this end, we prepared several humanized monoclonal IgA AGA using transgenic α1KI mice. Employing Pepscan with overlapping decapeptides of α-gliadin we observed a robust similarity between the specificity of humanized mouse monoclonal IgA AGA and IgA AGA from patients with florid CLD. The common immunodominant region included several sequential epitopes localized in the N-terminal part of α-gliadin (QFQGQQQPFPPQQPYPQPQPFP, aa 29-50, and QPFPSQQPYLQL, aa 47-58). Notably, IgA AGA produced by clones 8D12, 15B9, 9D12, and 18E2 had significant reactivity against sequences localized in the 33-mer, LQLQPFPQPQ (aa 56-65) and PQLPYPQPQPFL (aa 69-80). Humanized mouse monoclonal IgA AGA that have a known specificity are suitable as standard in ELISAs to detect serum IgA AGA of CLD patients and for studying the AGA pathogenic role in CLD, especially for analyzing the translocation of complex of specific IgA antibodies and individual gliadin peptides through enterocyte barrier. PMID:21366336

  10. The necessity and effectiveness of mineralocorticoid receptor antagonist in the treatment of diabetic nephropathy.

    Science.gov (United States)

    Sato, Atsuhisa

    2015-06-01

    Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic nephropathy is the most common primary disease necessitating dialysis treatment in the world including Japan. Major guidelines for treatment of hypertension in Japan, the United States and Europe recommend the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin-angiotensin system (RAS), as the antihypertensive drugs of first choice in patients with coexisting diabetes. However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects and a reduction in cardiovascular events has also been reported. Inadequate blockade of aldosterone may be one of the reasons why long-term administration of RAS inhibitors may not be sufficiently effective in patients with diabetic nephropathy. This review focuses on treatment in diabetic nephropathy and discusses the significance of aldosterone blockade. In pre-nephropathy without overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help to maintain 'long-term' antiproteinuric and anti-albuminuric effects. However, in category G3a and higher, sufficient attention must be paid to hyperkalemia. Mineralocorticoid receptor antagonists are not currently recommended as standard treatment in diabetic nephropathy. However, many studies have shown promise of better renoprotective effects if mineralocorticoid receptor antagonists are appropriately used. PMID:25762415

  11. Dynamic magnetic resonance imaging in the assessment of chronic medical nephropathies with impaired renal function

    Energy Technology Data Exchange (ETDEWEB)

    Dalla-Palma, L.; Pozzi-Mucelli, R.S.; Cova, M.; Meduri, S. [Dept. of Radiology, University of Trieste (Italy); Panzetta, G.; Galli, G. [Hemodialysis Service, Ospedale Maggiore, Trieste (Italy)

    2000-02-01

    We examined the value of dynamic magnetic resonance imaging (MRI) in chronic renal disease with renal insufficiency. In 33 consecutive patients (21 vascular nephropathy, 12 glomerular nephropathy) MRI was performed using a 1.5-T unit and a body coil, with SE T1-weighted (TR/TE = 600/19 ms) and dynamic TFFE T1-weighted sequences (TR/TE = 12/5 ms, flip angle = 25 ) after manual bolus injection (via a cubital vein) of 0.1 mmol/kg Gd-DTPA-BMA. Morphological evaluation was performed in unblinded fashion by three radiologists, evaluating renal size, cortical thickness, and corticomedullary differentiation. Functional analysis was performed by one reviewer. Time-signal intensity curves, peak intensity value (P), time to peak intensity (T), and the P/T ratio were obtained at the cortex, medulla, and pyelocaliceal system of each kidney. The relationship of these parameters to serum creatinine and with creatinine clearance was investigated. A good correlation between morphological features of the kidneys and serum creatinine values was found. Morphological findings could not distinguish between vascular and glomerular nephropathies. A statistically significant correlation (P <0.01) between cortical P, cortical P/T, medullary P, and serum creatinine and creatinine clearance was found. A significant correlation (P <0.01) was also found between cortical T, medullary P/T, T of the excretory system, and creatinine clearance. The cortical T value was significantly higher (P <0.01) in vascular nephropathy than in glomerular nephropathy. Thus in patients with chronic renal failure dynamic MRI shows both morphological and functional changes. Morphological changes are correlated with the degree of renal insufficiency and not with the type of nephropathy; the functional changes seem to differ in vascular from glomerular nephropathies. (orig.)

  12. Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Tamhane Umesh

    2009-05-01

    Full Text Available Abstract Background Contrast-induced nephropathy is the leading cause of in-hospital acute renal failure. This side effect of contrast agents leads to increased morbidity, mortality, and health costs. Ensuring adequate hydration prior to contrast exposure is highly effective at preventing this complication, although the optimal hydration strategy to prevent contrast-induced nephropathy still remains an unresolved issue. Former meta-analyses and several recent studies have shown conflicting results regarding the protective effect of sodium bicarbonate. The objective of this study was to assess the effectiveness of normal saline versus sodium bicarbonate for prevention of contrast-induced nephropathy. Methods The study searched MEDLINE, EMBASE, Cochrane databases, International Pharmaceutical Abstracts database, ISI Web of Science (until 15 December 2008, and conference proceedings for randomized controlled trials that compared normal saline with sodium bicarbonate-based hydration regimen regarding contrast-induced nephropathy. Random-effects models were used to calculate summary odds ratios. Results A total of 17 trials including 2,633 subjects were pooled. Pre-procedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced nephropathy (odds ratios 0.52; 95% confidence interval 0.34–0.80, P = 0.003. Number needed to treat to prevent one case of contrast-induced nephropathy was 16 (95% confidence interval 10–34. No significant differences in the rates of post-procedure hemodialysis (P = 0.20 or death (P = 0.53 was observed. Conclusion Sodium bicarbonate-based hydration was found to be superior to normal saline in prevention of contrast-induced nephropathy in this updated meta-analysis.

  13. Childhood Obesity. ERIC Digest.

    Science.gov (United States)

    Summerfield, Liane M.

    In this discussion of childhood obesity, the medical and psychological problems associated with the condition are noted. Childhood obesity most likely results from an interaction of nutritional, psychological, familial, and physiological factors. Three factors--the family, low-energy expenditure, and heredity--are briefly examined. Early…

  14. Reframing Early Childhood Leadership

    Science.gov (United States)

    Stamopoulos, Elizabeth

    2012-01-01

    Rapid changes in Australian education have intensified the role of early childhood leaders and led to unprecedented challenges. The Australian Curriculum (ACARA, 2011), mandated Australian "National Quality Framework" (NQF) for Early Childhood Education & Care (DEEWR, 2010b) and the "National Early Years Learning Framework" (EYLF) (DEEWR, 2009)…

  15. A System-Wide Approach to Diabetic Nephropathy

    KAUST Repository

    Palafox, Luis

    2011-07-07

    Diabetes mellitus is a complex human disease that affects more than 280 million people worldwide. One of the diabetic long-term complications is diabetic nephropathy that it is responsible for 50% of all end-stage renal disease. The complexity of diabetes and the lack of comprehensive systematic studies have halted the development of drugs and clinical therapies for the treatment of diabetes and its major complications. The present project, based on the db/db mice as animal model, investigates the repercussions of diabetes mellitus in the transcriptome as well as the mechanism of action of pirfenidone, an antifibrotic drug, in the treatment of diabetic nephropathy. The study was centered on the system-wide measurements transcriptional state of the mouse kidney. The expression profile of three experimental groups: control, diabetic, and diabetic treated with the drug, were analyzed using expression clustering, gene ontology enrichment analysis, protein-protein interaction network mapping, and gene expression behavior. The results show significant expression dysregulation of genes involved in RNA processing, fatty acid oxidation, and oxidative phosphorylation under the diabetic condition. The drug is able to regulate the expression levels of RNA processing genes but it does not show any effect in the expression profile of genes required in the oxidative phosphorylation and in the fatty acid metabolism. In conclusion diabetes mellitus induce the dysregulation of the splicing apparatus, the oxidative phosphorylation, and the fatty acid metabolic pathway at an expression level. The malfunction of these biological pathways causes cellular stress by increasing the concentration of reactive oxygen species within the cell due to a high oxidative and respiratory activity of mitochondria in addition to the increased demand of the folding machinery as a consequence of a dysregulation of the splicing apparatus. Pirfenidone regulates the expression of RNA processing genes mainly

  16. IgH loci of American alligator and saltwater crocodile shed light on IgA evolution.

    Science.gov (United States)

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-07-01

    Immunoglobulin loci of two representatives of the order Crocodylia were studied from full genome sequences. Both Alligator mississippiensis and Crocodylus porosus have 13 genes for the heavy chain constant regions of immunoglobulins. The IGHC locus contains genes encoding four immunoglobulins M (IgM), one immunoglobulin D (IgD), three immunoglobulins A (IgA), three immunoglobulins Y (IgY), and two immunoglobulins D2 (IgD2). IgA and IgD2 genes were found in reverse transcriptional orientation compared to the other Ig genes. The IGHD gene contains 11 exons, four of which containing stop codons or sequence alterations. As described in other reptiles, the IgD2 is a chimeric Ig with IgA- and IgD-related domains. This work clarifies the origin of bird IgA and its evolutionary relationship with amphibian immunoglobulin X (IgX) as well as their links with mammalian IgA. PMID:23558556

  17. Salivary IgA from the sublingual compartment as a novel noninvasive proxy for intestinal immune induction.

    Science.gov (United States)

    Aase, A; Sommerfelt, H; Petersen, L B; Bolstad, M; Cox, R J; Langeland, N; Guttormsen, A B; Steinsland, H; Skrede, S; Brandtzaeg, P

    2016-07-01

    Whole-saliva IgA appears like an attractive noninvasive readout for intestinal immune induction after enteric infection or vaccination, but has failed to show consistent correlation with established invasive markers and IgA in feces or intestinal lavage. For reference, we measured antibodies in samples from 30 healthy volunteers who were orally infected with wild-type enterotoxigenic Escherichia coli. The response against these bacteria in serum, lavage, and lymphocyte supernatants (antibody-in-lymphocyte-supernatant, ALS) was compared with that in targeted parotid and sublingual/submandibular secretions. Strong correlation occurred between IgA antibody levels against the challenge bacteria in sublingual/submandibular secretions and in lavage (r=0.69, PALS (r=0.70, Ptwofold ALS as a reference, the sensitivity of a >twofold response for IgA in sublingual/submandibular secretion was 96%, whereas it was only 67% in the parotid fluid. To exclude that flow rate variations influenced the results, we used albumin as a marker. Our data suggested that IgA in sublingual/submandibular secretions, rather than whole saliva with its variable content of parotid fluid, is a preferential noninvasive proxy for intestinal immune induction. PMID:26509875

  18. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    OpenAIRE

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; [...

    2015-01-01

    Background Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim of...

  19. Childhood trauma and childhood urbanicity in relation to psychotic disorder

    OpenAIRE

    Frissen, Aleida; Lieverse, Ritsaert; Drukker, Marjan; van Winkel, Ruud; Delespaul, Philippe; Cahn, W.

    2015-01-01

    BACKGROUND: Urban upbringing and childhood trauma are both associated with psychotic disorders. However, the association between childhood urbanicity and childhood trauma in psychosis is poorly understood. The urban environment could occasion a background of social adversity against which any effect of childhood trauma increases. Also, any impact of the urban environment on likelihood of exposure to childhood trauma could be stronger in children who later develop psychotic disorder. The aim o...

  20. Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yalena Amador-Ca(n)izares; Liz Alvarez-Lajonchere; Ivis Guerra; Ingrid Rodnguez-Alonso; Gillian Martínez-Donato; Julián Triana; Eddy E González-Horta; Angel Pérez; Santiago Due(n)as-Carrera

    2008-01-01

    AIM: In the present study, antibody and peripheral blood mononuclear cells (PBMC) proliferative responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients. METHODS: Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining.RESULTS: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P=0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P=0.017) and NS3 (P=0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P=0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized. CONCLUSION: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

  1. Alternative splicing of the human IgA Fc receptor CD89 in neutrophils and eosinophils.

    Science.gov (United States)

    Pleass, R J; Andrews, P D; Kerr, M A; Woof, J M

    1996-09-15

    Receptors for the Fc portion of IgA (Fc alpha R) trigger important immunological elimination processes against IgA-coated targets. Investigation of human Fc alpha R (CD89) transcripts in neutrophils, eosinophils and a monocyte-like cell line, THP-1, with the use of reverse transcriptase PCR, Northern blotting and RNase protection analysis, has provided evidence in these cell types for at least two distinct transcripts generated by alternative splicing. The cDNAs derived from the two major transcripts of both neutrophils and eosinophils have been cloned and sequenced. For both cell types, the larger clone represents the previously described full-length receptor, whereas the second, shorter, splice variant lacks the entire second, membrane-proximal, Ig-like domain. Stable CHO-K1 transfectants have been obtained for both full-length and truncated variant neutrophil receptors. Whereas the full-length receptor is recognized by a panel of five anti-Fc alpha R monoclonal antibodies (mAbs), the shorter variant is bound weakly by only two of the antibodies, suggesting that the epitopes recognized by the majority of the mAbs lie at least in part in the second Ig-like domain of Fc alpha R. Both full-length and splice variant forms of the receptor bind secretory IgA, but the weak binding to serum IgA seen with the full-length receptor is not evident with the shorter variant. Alternative splicing might therefore serve as a means of diversifying Fc alpha R structure and function. PMID:8836118

  2. Immunoglobulins in nasal secretions of healthy humans: structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

    DEFF Research Database (Denmark)

    Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper;

    2000-01-01

    . Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11......). IgA1 protease-producing bacteria (Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus mitis biovar 1) were isolated from the nasal cavities of seven subjects at 2.1 x 10(3) to 7.2 x 10(6) CFU per ml of undiluted secretion, corresponding to 0.2 to 99.6% of the flora. Nevertheless, alpha...

  3. Patients with primary membranous nephropathy are at high risk of cardiovascular events.

    Science.gov (United States)

    Lee, Taewoo; Derebail, Vimal K; Kshirsagar, Abhijit V; Chung, Yunro; Fine, Jason P; Mahoney, Shannon; Poulton, Caroline J; Lionaki, Sophia; Hogan, Susan L; Falk, Ronald J; Cattran, Daniel C; Hladunewich, Michelle; Reich, Heather N; Nachman, Patrick H

    2016-05-01

    Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy. PMID:26924046

  4. Association of Intercellular Adhesion Molecule 1 (ICAM1 with Diabetes and Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    HarvestFGu

    2013-01-01

    Full Text Available Diabetes and diabetic nephropathy are complex diseases affected by genetic and environmental factors. Identification of the susceptibility genes and investigation of their roles may provide useful information for better understanding of the pathogenesis and for developing novel therapeutic approaches. Intercellular adhesion molecule 1 (ICAM1 is a cell surface glycoprotein expressed on endothelial cells and leukocytes in the immune system. The ICAM1 gene is located on chromosome 19p13 within the linkage region of diabetes. In the recent years, accumulating reports have implicated that genetic polymorphisms in the ICAM1 gene are associated with diabetes and diabetic nephropathy. Serum ICAM1 levels in diabetes patients and the icam1 gene expression in kidney tissues of diabetic animals are increased compared to the controls. Therefore, ICAM1 may play a role in the development of diabetes and diabetic nephropathy. In this review, we present genomic structure, variation and regulation of the ICAM1 gene, summarized genetic and biological studies of this gene in diabetes and diabetic nephropathy and discussed about the potential application using ICAM1 as a biomarker and target for prediction and treatment of diabetes and diabetic nephropathy.

  5. Oxidative Stress/Angiotensinogen/Renin-Angiotensin System Axis in Patients with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Masumi Kamiyama

    2013-11-01

    Full Text Available Although recent studies have proven that renin-angiotensin system (RAS blockades retard the progression of diabetic nephropathy, the detailed mechanisms of their reno-protective effects on the development of diabetic nephropathy remain uncertain. In rodent models, it has been reported that reactive oxygen species (ROS are important for intrarenal angiotensinogen (AGT augmentation in the progression of diabetic nephropathy. However, no direct evidence is available to demonstrate that AGT expression is enhanced in the kidneys of patients with diabetes. To examine whether the expression levels of ROS- and RAS-related factors in kidneys are increased with the progression of diabetic nephropathy, biopsied samples from 8 controls and 27 patients with type 2 diabetes were used. After the biopsy, these patients were diagnosed with minor glomerular abnormality or diabetes mellitus by clinical and pathological findings. The intensities of AGT, angiotensin II (Ang II, 4-hydroxy-2-nonenal (4-HNE, and heme oxygenase-1 (HO-1 were examined by fluorescence in situ hybridization and/or immunohistochemistry. Expression levels were greater in patients with diabetes than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression paralleled renal dysfunction in patients with diabetes. These data suggest the importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of diabetic nephropathy.

  6. Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA myeloma.

    LENUS (Irish Health Repository)

    Ahmad, K

    2012-01-31

    We report a 57-year-old woman with a 12-year history of ulcerative pyoderma gangrenosum (PG). Five years after the onset of PG, she developed subcorneal pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG at two bone-marrow biopsy sites, showing pathergy. Finally, she developed multiple myeloma. Although PG and SPD may occur without associated underlying malignancy, these patients should be followed up for any prospective malignancy because of the association between these disorders.

  7. The relationship between salivary IgA levels and dental caries in children

    OpenAIRE

    E Ranadheer; Ullal Anand Nayak; N Venugopal Reddy; V Arun Prasad Rao

    2011-01-01

    Purpose: The aim of the study was to find the relationship between salivary IgA (s-IgA) levels and dental caries in children. Materials and Methods: A total of 40 children in the age group of 8 to 12 years were selected and divided into two groups. Group I with DMFT score 0 and Group II with DMFT score ≥3. The whole unstimulated s-IgA levels were estimated using ELISA method. Results: Whole s-IgA levels were significantly higher in group II with DMFT score ≥3 as compared with group I with DMF...

  8. Prognostic value of quantitative furosemide radionuclide renography in obstructive nephropathy

    International Nuclear Information System (INIS)

    Diuretic radionuclide renography is applied in patients with hydronephrosis in order to distinguish dilated, non-obstructed systems from those with significant mechanical obstruction. This is done after furosemide application by (semi) quantification of pelvic radioactivity outflow. In the dilated, non-obstructed pelvis, this outflow is increased, whereas in mechanical obstructed systems no response or even a decreased outflow is observed. It was expected that the latter outcome of the test is associated with an impaired renal function due to obstructive nephropathy. In the case that furosemide was given 30 min after 123I hippuran application, this assumption could not be proved. When furosemide and 123I hippuran were applied simultaneously, only a poor correlation was found between the response of pelvic outflow and the individual tubular clearance of the affected kidney. On the other hand, there was a clear correlation between the delay of pelvic outflow in the non-diuretic radionuclide renography and the individual tubular clearance. It can therefore be concluded that this test has little prognostic value and that other criteria in addition to the quantification of diuretic pelvic outflow are necessary for providing more reliable results. (orig.)

  9. Therapeutic approaches to diabetic nephropathy--beyond the RAS.

    Science.gov (United States)

    Fernandez-Fernandez, Beatriz; Ortiz, Alberto; Gomez-Guerrero, Carmen; Egido, Jesus

    2014-06-01

    Despite improvements in glycaemic and blood pressure control, and the efficacy of renin-angiotensin system (RAS) blockade for proteinuria reduction, diabetic nephropathy is the most frequent cause of end-stage renal disease in developed countries. This finding is consistent with the hypothesis that key pathogenetic mechanisms leading to progression of renal disease are not modified or inactivated by current therapeutic approaches. Although extensive research has elucidated molecular signalling mechanisms that are involved in progression of diabetic kidney disease, a number of high-profile clinical trials of potentially nephroprotective agents have failed, highlighting an insufficient understanding of pathogenic pathways. These include trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced-stage disease. Various strategies based on encouraging data from preclinical studies that showed renoprotective effects of receptor antagonists, neutralizing antibodies, kinase inhibitors, small compounds and peptide-based technologies are currently been tested in randomized controlled trials. Phase II clinical trials are investigating approaches targeting inflammation, fibrosis and signalling pathways. However, only one trial that aims to provide evidence for marketing approval of a potentially renoprotective drug (atrasentan) is underway-further research into the potential nephroprotective effects of novel glucose-lowering agents is required. PMID:24802062

  10. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  11. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy.

    Science.gov (United States)

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  12. Aristolochic acid nephropathy: epidemiology, clinical presentation, and treatment.

    Science.gov (United States)

    Luciano, Randy L; Perazella, Mark A

    2015-01-01

    Aristolochic acid (AA) is a compound extracted from the Aristolochia species of herbs. It has been used for centuries as a remedy for various illnesses and diseases. However, in the early 1990s in the setting of a weight loss herbal remedy, AA exposure was associated with a syndrome of kidney injury, termed aristolochic acid nephropathy (AAN). This entity is marked by elevated serum creatinine, significant anemia, and histopathologic changes demonstrating a hypocellular interstitial infiltrate with severe fibrosis. Progression towards end-stage renal disease (ESRD) is rapid, with most patients having chronic kidney disease for less than 2 years. In addition, AAN is associated with a 40-45 % prevalence of urothelial carcinomas. Treatment of AAN is limited to glucocorticoids that have been shown to delay progression in non-randomized trials. As most patients progress to ESRD, need for renal replacement therapy, as either dialysis or kidney transplant, usually ensues. However, given the high malignant potential, care must be taken to minimize future development of upper urinary tract cancers by performing prophylactic bilateral nephroureterectomies and aggressive cancer surveillance. PMID:25446374

  13. Risk score for contrast induced nephropathy following percutaneous coronary intervention

    International Nuclear Information System (INIS)

    Contrast-induced nephropathy (CIN) is an important cause of acute renal failure. Identification of risk factors of CIN and creating a simple risk scoring for CIN after percutaneous coronary intervention (PCI) is important. A prospective single center study was conducted in Kuwait chest disease hospital. All patients admitted to chest disease hospital for PCI from March to May 2005 were included in the study. Total of 247 patients were randomly assigned for the development dataset and 100 for the validation set using the simple random method. The overall occurrence of CIN in the development set was 5.52%. Using multivariate analysis; basal Serum creatinine, shock, female gender, multivessel PCI, and diabetes mellitus were identified as risk factors. Scores assigned to different variables yielded basal creatinine > 115 micron mol/L with the highest score(7), followed by shock (3), female gender, multivessel PCI and diabetes mellitus had the same score (2). Patients were further risk stratified into low risk score (12). The developed CIN model demonstrated good discriminative power in the validation population. In conclusion, use of a simple risk score for CIN can predict the probability of CIN after PCI; this however needs further validation in larger multicenter trials. (author)

  14. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

    Science.gov (United States)

    Gluhovschi, Gheorghe; Petrica, Ligia; Timar, Romulus; Velciov, Silvia; Ionita, Ioana; Kaycsa, Adriana; Timar, Bogdan

    2016-01-01

    Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

  15. MicroRNAs in Diabetic Nephropathy: From Biomarkers to Therapy.

    Science.gov (United States)

    Simpson, Kate; Wonnacott, Alexa; Fraser, Donald J; Bowen, Timothy

    2016-03-01

    Recent estimates suggest that 1 in 12 of the global population suffers from diabetes mellitus. Approximately 40 % of those affected will go on to develop diabetes-related chronic kidney disease or diabetic nephropathy (DN). DN is a major cause of disability and premature death. Existing tests for prognostic purposes are limited and can be invasive, and interventions to delay progression are challenging. MicroRNAs (miRNAs) are a recently described class of molecular regulators found ubiquitously in human tissues and bodily fluids, where they are highly stable. Alterations in miRNA expression profiles have been observed in numerous diseases. Blood and tissue miRNAs are already established cancer biomarkers, and cardiovascular, metabolic and immune disease miRNA biomarkers are under development. Urinary miRNAs represent a potential novel source of non-invasive biomarkers for kidney diseases, including DN. In addition, recent data suggest that miRNAs may have therapeutic applications. Here, we review the utility of miRNAs as biomarkers for the early detection and progression of DN, assess emerging data on miRNAs implicated in DN pathology and discuss how the data from both fields may contribute to the development of novel therapeutic agents. PMID:26973290

  16. Etiology of Balkan endemic nephropathy and associated urothelial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stefanovic, V.; Toncheva, D.; Atanasova, S.; Polenakovic, M. [Inst. of Nephrology and Hemodialysis, Nish (Serbia Montenegro)

    2006-07-01

    Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Evidence has accumulated that BEN is an environmentally induced disease. There are three actual theories attempting to explain the environmental cause of this disease: (1) the aristolochic acid hypothesis, which considers that the disease is produced by chronic intoxication with Aristolochia, (2) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A, and (3) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low-rank coals in the vicinity to the endemic settlements. Moreover, it was suggested that BEN risk is influenced by inherited susceptibility. Therefore, it has been expected that molecular biological investigations will discover genetic markers of BEN and associated urothelial cancer, permitting early identification of susceptible individuals who may be at risk of exposure to the environmental agents. Since kidney pathophysiology is complex, gene expression analysis and highly throughput proteomic technology can identify candidate genes, proteins and molecule networks that eventually could play a role in BEN development. Investigation of gene-gene and gene-environment interactions could be the content of further studies determining the precise risk for BEN.

  17. Prognostic factors and biomarkers of congenital obstructive nephropathy.

    Science.gov (United States)

    Chevalier, Robert L

    2016-09-01

    Congenital obstructive nephropathy (CON) is the leading cause of chronic kidney disease (CKD) in children. Anomalies of the urinary tract are often associated with abnormal nephrogenesis, which is compounded by obstructive injury and by maternal risk factors associated with low birth weight. Currently available fetal and postnatal imaging and analytes of amniotic fluid, urine, or blood lack predictive value. For ureteropelvic junction obstruction, biomarkers are needed for optimal timing of pyeloplasty; for posterior urethral valves, biomarkers of long-term prognosis and CKD are needed. The initial nephron number may be a major determinant of progression of CKD, and most patients with CON who progress to renal failure reach this point in adulthood, presumably compounded by episodes of acute kidney injury. Biomarkers of tubular injury may be of particular value in predicting the need for surgical intervention or in tracking progression of CKD, and must be adjusted for patient age. Discovery of new biomarkers may depend on "unbiased" proteomics, whereby patterns of urinary peptide fragments from patients with CON are analyzed in comparison to controls. Most promising are the analysis of urinary exosomes (restricting biomarkers to relevant tubular cells) and quantitative magnetic resonance imaging techniques allowing precise determination of nephron number and tubular mass. The greatest need is for large prospective multicenter studies with centralized biomarker sample repositories to follow patients with CON from fetal life through adulthood. PMID:26667236

  18. A case of primary JC polyomavirus infection-associated nephropathy.

    Science.gov (United States)

    Lautenschlager, I; Jahnukainen, T; Kardas, P; Lohi, J; Auvinen, E; Mannonen, L; Dumoulin, A; Hirsch, H H; Jalanko, H

    2014-12-01

    A 15-year-old boy with a posterior urethral valve received a deceased donor kidney transplant (KT) in March 2011. Basiliximab induction followed by tacrolimus-based triple medication was used as immunosuppression. Eleven months after KT, the graft function deteriorated and the biopsy demonstrated interstitial nephritis suggestive of acute rejection. BK polyomavirus (BKPyV) surveillance in urine and plasma was negative. The patient received methylprednisolone pulses and anti-thymocyte globulin. Immunohistochemistry was positive for simian virus 40 (SV40) large T-antigen (LTag) in the biopsies, and quantitative polymerase chain reaction for JC polyomavirus (JCPyV) indicated high viral loads in urine and borderline levels in plasma. Immunosuppression was reduced and follow-up biopsies showed tubular atrophy and interstitial fibrosis. Two years after KT, antibody-mediated rejection resulted in graft loss and return to hemodialysis. Retrospective serologic work-up indicated a primary JCPyV infection with seroconversion first for IgM, followed by IgG, but no indication of BKPyV infection. In the SV40 LTag positive biopsies, JCPyV deoxyribonucleic acid (DNA) with archetype noncoding control region was detected, while BKPyV DNA was undetectable. To the best of our knowledge, this is the first reported case of primary JCPyV infection as the cause of PyV-associated nephropathy in KT. PMID:25359127

  19. Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

    OpenAIRE

    Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H; Wu, Haifeng; Jon B Klein; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard

    2015-01-01

    …the residual risk of renal disease progression in patients with diabetic nephropathy is still extremely high despite current optimal treatment; innate immunity, MCP-1 and macrophage tissue infiltration seem very promising targets for future treatment of diabetic nephropathy on top of the standard of care with RAAS inhibition.

  20. Carnosine as a protective factor in diabetic nephropathy - Association with a leucine repeat of the carnosinase gene CNDP1

    NARCIS (Netherlands)

    Janssen, B; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, Stephan; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Koppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J.

    2005-01-01

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development o

  1. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1.

    Science.gov (United States)

    Janssen, Bart; Hohenadel, Daniela; Brinkkoetter, Paul; Peters, Verena; Rind, Nina; Fischer, Christine; Rychlik, Ivan; Cerna, Marie; Romzova, Marianna; de Heer, Emile; Baelde, Hans; Bakker, Stephan J L; Zirie, Mahmoud; Rondeau, Eric; Mathieson, Peter; Saleem, Moin A; Meyer, Jochen; Köppel, Hannes; Sauerhoefer, Sibylle; Bartram, Claus R; Nawroth, Peter; Hammes, Hans-Peter; Yard, Benito A; Zschocke, Johannes; van der Woude, Fokko J

    2005-08-01

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells. PMID:16046297

  2. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S;

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind the...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed...... reactive to whole HIV-2 antigen, and 14 of 15 reacted with rgp36. For rgp105 and gp125, 5 of 15 and 4 of 15 samples exhibited binding, respectively. The serum of the EGSN group had a higher mean IgA concentration than that of the negative controls (P < 0.05). Thus, we describe HIV-2-specific serum Ig...

  3. Childhood cancer in Africa.

    Science.gov (United States)

    Kruger, Mariana; Hendricks, Marc; Davidson, Alan; Stefan, Cristina D; van Eyssen, Ann L; Uys, Ronelle; van Zyl, Anel; Hesseling, Peter

    2014-04-01

    The majority of children with cancer live in low- and middle-income countries (LMICs) with little or no access to cancer treatment. The purpose of the paper is to describe the current status of childhood cancer treatment in Africa, as documented in publications, dedicated websites and information collected through surveys. Successful twinning programmes, like those in Malawi and Cameroon, as well as the collaborative clinical trial approach of the Franco-African Childhood Cancer Group (GFAOP), provide good models for childhood cancer treatment. The overview will hopefully influence health-care policies to facilitate access to cancer care for all children in Africa. PMID:24214130

  4. Analgesic nephropathy as a cause of end-stage renal disease in a 55 year-old Nigerian.

    Science.gov (United States)

    Okafor, U H; Unuigbe, E I; Onwuchekwa, A C; Emem-Chioma, P

    2012-01-01

    Analgesic nephropathy is a subtle but significant cause of chronic renal failure. There is paucity of data on analgesic nephropathy in Nigeria. This case presentation is to highlight the need to have high index of suspicion in patients at risk of developing analgesic nephropathy. In March 2009 a 55-year-old businessman was referred to the renal unit on account of azotemia by the hematologist who had hitherto managed the patient as a case of refractory anemia. The patient had osteoarthritis for over 10 years and was managed with several analgesic drugs over the same period. He was found to have features suggestive of analgesic nephropathy and had end-stage renal disease. He was commenced on appropriate therapy, and he had a live related kidney transplant six months later. Analgesic nephropathy is preventable and morbidity/mortality can be remarkably reduced with appropriate and prompt intervention. PMID:22718180

  5. Natural Immunoreactivity of Secretory IgA to Indigenous Strains of Streptococcus mutans From Chinese Spousal Pairs

    Science.gov (United States)

    Nie, Min; Chen, Dong; Gao, Zhenyan; Wu, Xinyu; Li, Tong

    2016-01-01

    Background Dental caries is a well-known biofilm-mediated disease initiated by Streptococcus mutans, which should infect and colonize in a milieu perfused with components of the mucosal immune system. Little is known, however, regarding the relationship between the natural secretory IgA activity and S. mutans of a variety of diverse genotypes. Objectives The current study aimed to use spousal pairs to investigate the natural immunoreactivity of salivary secretory IgA to different genotype strains of S. mutans. Patients and Methods Indigenous strains were characterized from nine spousal pairs using polymerase reaction chain (PCR) and arbitrarily primed polymerase chain reaction (AP-PCR) by genotype monitoring. Unstimulated submandibular/sublingual secretions were collected and the concentrations of secretory IgA were determined by the enzyme-linked immunosorbent assay (ELISA). Each saliva sample was examined by Western blot to analyze the immunoreactivity of naturally occurring salivary secretory IgA antibodies for his/her own indigenous strain, spouse’s strain and reference strains including S. mutans GS-5 and Ingbritt (C). Results The results showed that naturally induced salivary IgA antibodies against S. mutans were present in all subjects. Almost all subjects had the similar individual immunoblotting profiles to different genotype strains. Conclusions The current study indicated that the immunoreactivity of secretory IgA might have no direct correlation with the colonization of indigenous flora and rejection of exogenous strains in adults. The relationship of microbes, host and dental caries should be in the light of coevolved microecosystem as a whole, but not caused by one factor alone. PMID:27303613

  6. Contrast-medium-induced nephropathy: is there a new consensus? A review of published guidelines

    International Nuclear Information System (INIS)

    The interest in contrast-medium-induced nephropathy has increased considerably during the last few years. Various guidelines regarding identifying patients at risk and measures to reduce the incidence of this complication have been proposed. The aim of this review was to analyse whether there is some consistency amongst these guidelines. A Medline search for the keyword ''contrast medium induced nephropathy'' during the period from the beginning of 2003 through the end of September 2005 was carried out. Only papers in English were reviewed. Thirteen guidelines were identified. Inconsistency was observed regarding advise on the prophylactic use of drugs and the isoosmolar dimer to reduce the incidence of contrast-medium-induced nephropathy. Consistency was found in relation to the importance of hydration, cessation of intake of nephrotoxic drugs and administration of the lowest possible dose of contrast medium. No new consensus has been observed in comparison to the European Society for Urogenital Radiology (ESUR) guidelines, which were published in 1999. (orig.)

  7. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    Science.gov (United States)

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  8. ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.

    Science.gov (United States)

    Hanson, Robert L; Millis, Meredith P; Young, Naomi J; Kobes, Sayuko; Nelson, Robert G; Knowler, William C; DiStefano, Johanna K

    2010-12-01

    Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polymorphisms in mediating susceptibility to this disease in this population. Genotype distributions were compared among 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships, and 107 cases with diabetic ESRD and 108 controls with long duration diabetes and no nephropathy. We sequenced 17.4 kb of ELMO1 and identified 19 variants. We genotyped 12 markers, excluding those in 100% genotypic concordance with other variants or with a minor allele frequency ELMO1 variation may involve as yet undiscovered functional variants or complex interactions with other biological variables. PMID:20826100

  9. A case of primary renal allograft dysfunction due to myeloma cast nephropathy

    Directory of Open Access Journals (Sweden)

    Umesh Lingaraj

    2015-01-01

    Full Text Available We report a rare case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical features of multiple myeloma preceding his transplantation. A 45-year-old man on hemodialysis for six months for end-stage kidney disease due to presumed chronic glomerulonephritis developed immediate graft dysfunction post-transplantation. The graft biopsy was diagnostic of myeloma cast nephropathy. Other criteria for lambda light chain multiple myeloma were fulfilled with immunofixation electrophoresis and bone marrow biopsy. He was treated with plasmapheresis, bortezomib and high-dose dexamethasone. However, the patient succumbed to septicemia on the 37 th post-operative day. This is probably the first report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week posttransplanation in a patient with unrecognized multiple myeloma.

  10. A comparison of spirapril and isradipine in patients with diabetic nephropathy and hypertension

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Christensen, P; Feldt-Rasmussen, B

    1993-01-01

    The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were...... studied. All had hypertension and diabetic nephropathy with a urinary albumin excretion of more than 300 mg/24 h. After a single blind placebo treatment period of 4 weeks the patients were randomly assigned to treatment with the calcium antagonist isradipine SRO 5 mg once daily or the ACE inhibitor...... vs 2636 +/- 194 meq/1.73 m2 (p < 0.05) and extracellular volume tended to do so (p = 0.12). On isradipine treatment these parameters remained unchanged. In conclusion both isradipine and spirapril lowered blood pressure in patients with diabetic nephropathy. Only the ACE inhibitor had demonstrable...

  11. Kopsuvähk luurab koolimajas : Põhikooli lõpulkassis suitsetab iga neljas Tallinna koolilaps / Birgit Püve, Juhani Püttsepp

    Index Scriptorium Estoniae

    Püve, Birgit, 1978-

    2003-01-01

    Tallinna koolide õpilaste suitsetamisest ja koolijuhtide suhtumisest sellesse. Eesti Tervisekasvatuse keskuse ja Tallinna haridusameti 2002. a. lõpul valminud uuringust selgub, et seitsmendas klassis suitsetab iga 10. Tallinna koolilaps, üheksandas aga juba iga 4. Tallinna koolilaps suitsetab rohkem kui tema eakaaslane Eestis keskmiselt

  12. IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Bode, C.

    2002-01-01

    , endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...

  13. Streptococcal IgA-binding proteins bind in the Calpha 2-Calpha 3 interdomain region and inhibit binding of IgA to human CD89.

    Science.gov (United States)

    Pleass, R J; Areschoug, T; Lindahl, G; Woof, J M

    2001-03-16

    Certain pathogenic bacteria express surface proteins that bind to the Fc part of human IgA or IgG. These bacterial proteins are important as immunochemical tools and model systems, but their biological function is still unclear. Here, we describe studies of three streptococcal proteins that bind IgA: the Sir22 and Arp4 proteins of Streptococcus pyogenes and the unrelated beta protein of group B streptococcus. Analysis of IgA domain swap and point mutants indicated that two loops at the Calpha2/Calpha3 domain interface are critical for binding of the streptococcal proteins. This region is also used in binding the human IgA receptor CD89, an important mediator of IgA effector function. In agreement with this finding, the three IgA-binding proteins and a 50-residue IgA-binding peptide derived from Sir22 blocked the ability of IgA to bind CD89. Further, the Arp4 protein inhibited the ability of IgA to trigger a neutrophil respiratory burst via CD89. Thus, we have identified residues on IgA-Fc that play a key role in binding of different streptococcal IgA-binding proteins, and we have identified a mechanism by which a bacterial IgA-binding protein may interfere with IgA effector function. PMID:11096107

  14. Comparative study on the development of intestinal mucin 2, IgA and polymeric Ig receptor expressions between broiler chickens and Pekin ducks

    Science.gov (United States)

    Intestinal mucin2 (MUC2), a major gel-forming mucin, represents a primary barrier component of mucus layers and target site for secretory IgA. Polymeric Ig receptor (pIgR) expressed on the basolateral surface of epithelium, is used to transport polymeric IgA from the lamina propria into luminal muci...

  15. Effects of feeding whey protein on growth rate and mucosal IgA induction in Japanese Black calves

    OpenAIRE

    Yasumatsuya, Keiko; Kasai, Koji; Yamanaka, Kengo; SAKASE, Mitsuhiro; Nishino, Osamu; Akaike, Masaru; Mandokoro, Koki; Nagase, Tatsuo; Kume, Shinichi

    2012-01-01

    Data from 63 Japanese Black calves were collected to clarify the effects of feeding whey protein on the growth rate and mucosal IgA induction in calves. Dietary treatments in milk replacers were 1) 26% CP as in skim milk (control), 2) 26% CP as whey and skim milk and 3) 26% CP as whey. Diets were offered from 3 to 63 days of age in calves. Feeding whey protein had no effects on growth rate, fecal consistency and fecal water in calves. Compared with 2 days of age, fecal IgA concentration in ca...

  16. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency

    OpenAIRE

    Olsson, Mia; Tengvall, Katarina; Frankowiack, Marcel; Kierczak, Marcin; Bergvall, Kerstin; Axelsson, Erik; Tintle, Linda; Marti, Eliane; Roosje, Petra; Leeb, Tosso; Hedhammar, Åke; Hammarström, Lennart; Lindblad-Toh, Kerstin

    2015-01-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a com...

  17. Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency.

    OpenAIRE

    Olsson, Mia; Tengvall, Katarina; Frankowiack, Marcel; Kierczak, Marcin; Bergvall, Kerstin; Axelsson, Erik; Tintle, Linda; Marti, Eliane Isabelle; Roosje, Petra; Leeb, Tosso; Hedhammar, Åke; Hammarström, Lennart; Lindblad-Toh, Kerstin

    2015-01-01

    Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a com...

  18. Milk protein IgG and IgA: The association with milk-induced gastrointestinal symptoms in adults

    OpenAIRE

    Petroviæ Marina

    2009-01-01

    AIM: To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults.METHODS: Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland. Subjects were randomly selected from a total of 1900 adults undergoing laboratory investigations in primary care. All 400 participants had completed a questionnaire on abdominal symptoms and dairy consumption w...

  19. Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children

    OpenAIRE

    Fagerås Böttcher, Malin; Tomicic, Sara; Voor, Tiia; Björkstén, Bengt; Jenmalm, Maria

    2011-01-01

    It is unknown why allergic symptoms do not develop in all sensitized children. We analyzed prospectively the postnatal secretory IgA (SIgA) development and whether high SIgA levels would protect sensitized infants from developing allergic symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically adjacent countries with diff...

  20. Radioimmunoassay of IgM, IgG, and IgA brucella antibodies

    International Nuclear Information System (INIS)

    A radioimmunoassay (R.I.A.) has been devised to measure the serum antibody against Brucella abortus in each of the immunoglobulin classes IgM, IgG, and IgA. This test was applied to 46 sera from individuals with various clinical types of brucellosis, and the results were compared with the results of conventional direct and indirect agglutination and complement-fixation tests. The R.I.A. provided a highly sensitive primary-type assay which avoided the difficulties with blocking or non-agglutinating antibody, and thus has many advantages in the diagnosis of acute and chronic stages of brucella infection in man. The R.I.A. was successful in detection of antibody in many instances in which conventional serological tests were negative, and such antibody could (if IgM) be associated with acute or (if IgG or IgA) with chronic cases of brucellosis. One case in which B.abortus was isolated by blood culture but which failed to yield antibody by conventional tests, nevertheless showed substantial levels of IgM and IgG antibody by R.I.A. In other cases the R.I.A. test helped to eliminate the diagnosis of brucellosis by revealing absent or low antibody levels. (author)

  1. Indigeneity-Grounded Analysis (IGA as Policy(-Making Lens: New Zealand Models, Canadian Realities

    Directory of Open Access Journals (Sweden)

    Roger Maaka

    2010-05-01

    Full Text Available Engaging politically with the principles of indigeneity is neither an option nor a cop out. The emergence of Indigenous peoples as prime-time players on the world’s political stage attests to the timeliness and relevance of indigeneity in advancing a new postcolonial contract for living together differently. Insofar as the principles of indigeneity are inextricably linked with challenge, resistance, and transformation, this paper argues that reference to indigeneity as policy(- making paradigm is both necessary and overdue. To put this argument to the test, the politics of Maori indigeneity in Aotearoa New Zealand are analyzed and assessed in constructing an indigeneity agenda model. The political implications of an indigeneity-policy nexus are then applied to the realities of Canada’s Indigenous/Aboriginal peoples. The paper contends that, just as the Government is committed to a gender based analysis (GBA for improving policy outcomes along gender lines, so too should the principles of indigeneity (or aboriginality secure an indigeneity grounded analysis (IGA framework for minimizing systemic policy bias while maximizing Indigenous peoples inputs. The paper concludes by theorizing those provisional first principles that inform an IGA framework as a policy (-making lens.

  2. Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.

    Science.gov (United States)

    Li, Hao; Li, Min; Liu, Ping; Wang, YaPing; Zhang, Heng; Li, HongBin; Yang, ShiFeng; Song, Yan; Yin, YanRong; Gao, Lan; Cheng, Si; Cai, Jun; Tian, Gang

    2016-08-01

    Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. PMID:27296996

  3. Cardiovascular Conditions of Childhood

    Science.gov (United States)

    ... This childhood illness can result in long-term heart complications. Learn the symptoms, diagnosis and treatment for Kawasaki disease. Rheumatic Fever This inflammatory infection can occur after strep ...

  4. Reducing Childhood Obesity

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  5. Childhood Immunization Schedule

    Science.gov (United States)

    ... Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get the ... See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of age ...

  6. Childhood vitiligo: Treatment paradigms

    Directory of Open Access Journals (Sweden)

    Amrinder Jit Kanwar

    2012-01-01

    Full Text Available Childhood vitiligo differs from the adults by showing a higher incidence in females, segmental vitiligo being more common and less frequent association with other systemic autoimmune and endocrine disorders.Childhood vitiligo is often associated with a marked psychosocial and long lasting effect on the self-esteem of the affected children and their parents, hence an adequate treatment is very essential. Treatment of vitiligo is indeed a tough challenge for the dermatologists′ more so in the background of childhood vitiligo. Although multiple therapeutic modalities are available in the therapeutic armamentarium, not all can be used in children. This brief report updates regarding various therapies available in the treatment of childhood vitiligo.

  7. Childhood Vaccine Schedule

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  8. Tooth decay - early childhood

    Science.gov (United States)

    ... Ribeiro NM, Ribeiro MA. Breastfeeding and early childhood caries: a critical review. J Pediatr (Rio J) . 2004;80:S199-S210. Sexton S, Natale R. Risks and benefits of pacifiers. Am Fam Physician . 2009; ...

  9. Early Childhood Caries

    OpenAIRE

    Kawashita, Yumiko; Kitamura, Masayasu; Saito, Toshiyuki

    2011-01-01

    Dental caries is one of the most common childhood diseases, and people continue to be susceptible to it throughout their lives. Although dental caries can be arrested and potentially even reversed in its early stages, it is often not self-limiting and progresses without proper care until the tooth is destroyed. Early childhood caries (ECC) is often complicated by inappropriate feeding practices and heavy infection with mutans streptococci. Such children should be targeted with a professional ...

  10. Endobronchial tumours in childhood

    International Nuclear Information System (INIS)

    Endobronchial tumours are rare in childhood and are not often considered in the differential diagnosis of persistent pneumonitis and atelectasis. We present the clinical and radiological features of seven cases of childhood bronchial 'adenoma' seen at our hospital over a 16-year period. Because they are relatively slow growing, prompt diagnosis and early surgical treatment offer the best chance of cure in these patients. A review of the literature is given

  11. Abdominal MRI in childhood

    International Nuclear Information System (INIS)

    MRI provides diagnostic information in multiple abdominal diseases in childhood. Additional information to sonographic findings can be achieved in the diagnosis of abdominal malformation as well as in several inflammatory processes. In childhood cancer imaging MRI is essential at the beginning as well as during therapy to assess response to therapy. Because of radiation protection MRI has to replace CT in abdominal imaging in children. Some technical details have to be considered when children are examined. (orig.)

  12. Meningeal hemangiopericytoma in childhood

    International Nuclear Information System (INIS)

    Meningeal hemangiopericytoma (MHP) is extremely rare in childhood. Mean age at diagnosis is between 38 and 43 years. We present an 8-year-old boy with MHP of the middle cranial fossa. Imaging findings were indistinguishable from an aggressive bone tumor such as Ewing's sarcoma. Imaging findings are presented and discussed. Our case indicates that MHP should be considered in the differential diagnosis of skull-base tumors despite the fact that MHP is extremely rare in childhood. (orig.)

  13. Endobronchial tumours in childhood

    International Nuclear Information System (INIS)

    Endobronchial tumours are rare in childhood and are not often considered in the differential diagnosis of persistent pneumonitis and atelectasis. We present the clinical and radiological features of seven cases of childhood bronchial 'adenoma' seen at our hospital over a 16-year period. Because they are relatively slow growing, prompt diagnosis and early surgical treatment offer the best chance of cure in these patients. A review of the literature is given. (Copyright (c) Elsevier Science B.V., Amsterdam. All rights reserved.)

  14. Fractures in childhood

    International Nuclear Information System (INIS)

    Clinical diagnosis of fractures in childhood can be very difficult. Therefore imaging, not only x-rays but also ultrasound, computed tomography and magnetic resonance imaging are of special importance. There are typical pediatric types of fractures due to epiphyseal plates and high flexibility of the bone. Fractures heal faster and dislocations can be spontaneously corrected better but also growth disturbance can occur. The second part of the article describes the special types of fractures with special attention to the characteristics in childhood.

  15. Stress and childhood epilepsy

    OpenAIRE

    Campen, J.S. van

    2015-01-01

    Epilepsy is one of the most common chronic diseases in childhood, characterized by the enduring predisposition to generate epileptic seizures. Children with epilepsy and their parents often report seizures precipitated by stress. In order to increase our understanding of the pathophysiological mechanisms underlying the effects of stress on seizures in childhood epilepsy, we performed a variety of studies, which are described in this thesis. In part I we evaluate the extent of stress sensitivi...

  16. Early childhood aggression

    OpenAIRE

    Alink, Lenneke Rosalie Agnes

    2006-01-01

    In this thesis the development, stability, and correlates of early childhood aggression were investigated. The normative development was examined in a general population sample using questionnaires completed by the parents of 12-, 24-, and 36-month-old children and again one year later. Results showed an early childhood aggression curve, with increasing rates of aggression in the second year of life and decreasing rates in the fourth year. One-year stabilities were moderate for 12-month-olds ...

  17. Pesticides and childhood cancers.

    OpenAIRE

    Daniels, J L; Olshan, A.F.; Savitz, D A

    1997-01-01

    To evaluate the possible association between pesticides and the risk of childhood cancers, epidemiologic studies published between 1970 and 1996 were critically reviewed. Thirty-one studies investigated whether occupational or residential exposure to pesticides by either parents or children was related to increased risk of childhood cancer. In general, the reported relative risk estimates were modest. Risk estimates appeared to be stronger when pesticide exposure was measured in more detail. ...

  18. Childhood Ovarian Malignancy

    OpenAIRE

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-01-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4...

  19. Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Brunskill Eric W

    2012-07-01

    Full Text Available Abstract Background Diabetic nephropathy is the leading cause of end stage renal disease. All three cell types of the glomerulus, podocytes, endothelial cells and mesangial cells, play important roles in diabetic nephropathy. In this report we used Meis1-GFP transgenic mice to purify mesangial cells from normal mice and from db/db mice, which suffer diabetic nephropathy. The purpose of the study is to better define the unique character of normal mesangial cells, and to characterize their pathogenic and protective responses during diabetic nephropathy. Methods Comprehensive gene expression states of the normal and diseased mesangial cells were defined with microarrays. By comparing the gene expression profiles of mesangial cells with those of multiple other renal cell types, including podocytes, endothelial cells and renal vesicles, it was possible to better define their exceptional nature, which includes smooth muscle, phagocytic and neuronal traits. Results The complete set of mesangial cell expressed transcription factors, growth factors and receptors were identified. In addition, the analysis of the mesangial cells from diabetic nephropathy mice characterized their changes in gene expression. Molecular functions and biological processes specific to diseased mesangial cells were characterized, identifying genes involved in extracellular matrix, cell division, vasculogenesis, and growth factor modulation. Selected gene changes considered of particular importance to the disease process were validated and localized within the glomuerulus by immunostaining. For example, thrombospondin, a key mediator of TGFβ signaling, was upregulated in the diabetic nephropathy mesangial cells, likely contributing to fibrosis. On the other hand the decorin gene was also upregulated, and expression of this gene has been strongly implicated in the reduction of TGFβ induced fibrosis. Conclusions The results provide an important complement to previous studies

  20. Resolution of a proteinuric nephropathy associated with Babesia gibsoni infection in a dog.

    Science.gov (United States)

    Slade, Dennis J; Lees, George E; Berridge, Brian R; Clubb, Fred J; Kuczynski, Leslie A; Littman, Meryl P

    2011-01-01

    A 4 yr old male castrated Labrador retriever was evaluated for a short history of inappetance, lethargy, small-bowel diarrhea, polyuria, and polydipsia. Clinicopathologic abnormalities were consistent with protein-losing nephropathy and renal azotemia. Expansive infectious disease testing implicated Babesia gibsoni via whole blood polymerase chain reaction. Renal histopathology results were consistent with membranoproliferative glomerulonephritis and immune complex deposition. The dog was treated with azithromycin, atovaquone, and one dose of corticosteroids/cyclophosphamide. Three months after therapy was completed, the dog was clinically healthy, and all clinicopathologic abnormalities (including Babesia species polymerase chain reaction) had resolved. Atypical presentations of Babesia gibsoni should be considered with proteinuric nephropathy. PMID:22058361