Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidized low-density lipoproteins (Ox-LDL) have been shown to be involved in the pathogenesis of atherosclerosis. Because of the similarities between atherosclerosis and focal glomerulosclerosis, a study was performed to demonstrate whether Ox-LDL could be detected in the glomeruli in experimental FGS. FGS was induced in 12 rats on a 4% cholesterol-1% choline diet by seven injections of puromycin aminonucleoside over a 10 week period. Eight rats on a normal diet served as controls. Fourteen weeks after the start of the experiment all rats were sacrificed. The test animals showed marked hypercholesterolemia and proteinuria. About 20% of glomeruli in test animals showed FGS and variable amounts of glomerular lipid were demonstrated. Immunohistochemical staining using five specific monoclonal antibodies against various forms of Ox-LDL showed positive staining of a variable number of glomeruli in the test rats. The staining pattern appeared to be intracellular. Staining with ED1 showed significantly increased numbers of intraglomerular monocytes in the test rats (test vs. control 2.4 +/- 1.1 vs. 0.4 +/- 0.1 monocytes per glomerulus, P < 0.0001). Control animals showed no segmental sclerosis, no glomerular lipid, and no staining for Ox-LDL. Lipid analysis of isolated glomeruli showed increased cholesterol, increased arachidonic acid and decreased eicosapentaenoic acid in test animals compared to controls. The findings suggest a role for Ox-LDL in the pathogenesis of experimental FGS and support the hypothesis that FGS is analogous to atherosclerosis.
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PMID:Oxidized low-density lipoprotein in experimental focal glomerulosclerosis. 831 38

Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA-associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long-term outcome of renal transplant patients with biopsy-proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long-term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy-four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow-up: the functioning graft group (n = 30) and the graft-loss group (n = 44). There was no significant difference in severity of CAA grade between the functioning and graft-loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA-associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow-up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non-specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long-term CSA treatment.
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PMID:Chronic cyclosporin nephropathy: long-term effects of cyclosporin on renal allografts. 1179 91

Glomerulosclerosis is a common morphologic result seen in almost all progressed renal diseases, and is the characteristic change in focal segmental glomerulosclerosis (FSGS). The most convincing hypothesis for glomerulosclerosis is cytokine-mediated injury by infiltrating immune cells in the glomerulus and tubulointerstitial area. This study investigated whether the anti-inflammatory effect of interleukin-10 (IL-10) when expressed by a recombinant adenoviral vector can prevent the onset of glomerulosclerosis in FGS/Kist mice (an animal model with naturally occurring renal failure initiated by FSGS). Each group of mice received recombinant adenoviruses encoding human IL-10 (Ad:hIL-10) by intraparenchymal injection at 6 weeks and were examined for cytokine expression, glomerular sclerotic index, and proteinuria. After injection of Ad:hIL-10 to the kidney, IL-10 expression was found to last over 20 days. Mice treated with Ad:hIL-10 were shown to have a significant reduction in the glomerular sclerotic index at 10 weeks when compared to control groups. The level of proteinuria in Ad:hIL-10-treated mice was also significantly reduced. About 50% of the urine samples of naive and Ad:LacZ-treated groups had severe levels of proteinuria. By contrast, at 10 weeks the group treated with Ad:hIL-10 had lower levels of proteinuria and transforming growth factor-beta1 (TGF-beta1) expression. These results demonstrate that IL-10 effectively prevents the development of glomerulosclerosis in FGS/Kist mice, and IL-10 gene therapy may be of use for the treatment of renal failure.
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PMID:Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney. 1264 61

Pirfenidone (PFD) is a newly developed anti-fibrotic agent. We evaluated the effect of PFD for the prevention of renal fibrosis using a spontaneous progressive glomerulosclerosis animal model, FGS/Kist mice. Male and female FGS/Kist mice were fed a diet containing 0.5% PFD or the same control diet (CD) without PFD, for 1, 2, or 3-month periods. Body weight was monitored for the general effect of PFD on the mice. Proteinuria and glomerular filtration rate (GFR) were evaluated for renal function. The sclerosis index was examined for the morphological changes. There were no significant changes in body weight between the PFD and control groups in both sexes. Proteinuria levels were low in all the PFD groups compared to the corresponding CD groups. The sclerosis scores were also reduced in both sexes of the 3-month PFD groups (p<0.05), and glomerular filtration rates were increased in both sexes of the 3-month PFD groups compared to the CD groups. The treatment of PFD for 1 or 2-month periods did not have statistic significances but the treatment for 3 months had statistic significances in sclerosis and GFR compared to CD groups. These results suggested that long-term administration of PFD suppressed the progression of glomerulosclerosis and improved renal function of the FGS/Kist mice.
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PMID:Pirfenidone suppressed the development of glomerulosclerosis in the FGS/Kist mouse. 1292 29

Within recent years the number of children with focal segmental glomerulonephritis (FSGS) has increased. A significant progress in defining of molecular basis of the disease has been made. Gene mutations for nephrin, podocin, WT1, alpha-actinin 4 cause the damage of filtration barrier of glomerulus and proteinuria in consequence. A girl (S.G.) became ill at the age of 3.5, suffering form steroid-resistant nephritic syndrome (SRNS) with microscopic hematuria. The renal biopsy showed FSGS accompanied by a complete diffuse effacement of podocyte food processes. Despite intensive and regular immunosuppressive therapy, remission was not achieved. In the control renal biopsy performed a year after cyclosporin A had been applied, 50% of globally sclerosed glomeruli as well as some features of post-cyclosporin damage were found. The girl required renal replacement therapy at the age of 10.5. Dialyzed at the adult dialysis centre she died at the age of 11.5. A boy S.P. was diagnosed with SRNS when he was 11.5 years old. The renal biopsy was performed after one month of treatment and showed mesangial proliferation and diffuse effacement of podocyte food processes. After chlorambucil treatment remission was not achieved, and after methylprednisolon pulse therapy only the reduction of proteinuria was achieved. In a control renal biopsy 10 out of 13 glomeruli were globally sclerosed. At the age of 17 the patient showed chronic renal failure with a fast progression of the disease. In September 2000 the boy started renal replacement therapy, an in June 2001 he received a renal transplant without the recurrence of FGS. In 2001 a heterozygous mutation (A284V) in gene NPHS2 was found in both of the siblings. Within the confines of the clinical project ESCAPE Trial another genetic examination was performed. In the boy one missense mutation on one allele (A284V) and the R229Q polymorphism on the other allele were found. In this family the father is bear. ing the A284V mutation and the mother the R229Q variant. These results prove that this disease is due to alterations of the podocin gene in the described family.
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PMID:[Heterozygotic mutation in NPHS2 gene as a cause of familial steroid resistant nephrotic syndrome in two siblings--case report]. 1689 97


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