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)

Rats were injected with a single intravenous dose of aminonucleoside (AMN) and sacrificed 1-48 h later. The activity of several enzymes was assayed in the Golgi apparatus isolated from the liver. Galactosyltransferase activity showed little changes after the AMN, but both acid (EC 3.1.3.2) and alkaline phosphatase (EC 3.1.3.1) activities increased within the first hour and reached control levels only 5-24 h later. Thiamine pyrophosphatase and arylsulfatase A (EC 3.1.6.1) activities also increased and stayed at higher levels for the duration of the experiment. Arylsulfatase B (EC 3.1.6.1) activity decreased shortly after the AMN but later increased to above control levels. These findings support earlier results in which liver ultrastructural and biochemical changes were observed early before renal lesions and proteinuria.
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PMID:Early effects of aminonucleoside on enzymes in the Golgi apparatus of rat liver. 24 Apr 92

To study the role of lysosomal enzymes in glomeruli, we examined specific activities of lysosomal hydrolases in isolated glomeruli and, for comparison in isolated tubules, from rat kidney cortex of normal animals and animals with puromycin aminonucleoside nephrosis (PAN). Nephrotic syndrome was induced in rats by a single intraperitoneal injection of aminonucleoside and the rats were sacrificed at the time of peak proteinuria. Colloidal iron staining of renal cortex demonstrated decreased staining for the epithelial polyanion in animals with PAN. Lysosomal enzymes were determined by fluorogenic and colorimetric methods. In normal kidney, total specific activities of cathepsin beta 1, beta-2-fucosidase, acetyl-beta-glucosaminidase, and arylsulfatase were lower in glomeruli compared with tubules and with tissue slices of the same kidney. Total activity of acid phosphatase was higher in glomeruli than tubules. In glomeruli of PAN rats, there were lower activities of N-acetyl-beta-glucosaminidase, D-fucosidase, beta-glucosidase, beta-glucoronidase, and arylsulfatase compared with control rats. Activity of acid phosphatase, on the other hand, was higher in glomeruli of PAN than control rats. All differences were statistically significant. These studies demonstrate that (1) activities of lysosomal enzymes in normal glomeruli and in glomeruli of nephrotic rats have a property distinct from the rest of the kidney, and (2) the specific activities of lysosomal hydrolases are altered in glomeruli of rats with PAN. These studies suggest that changes in activities of lysosomal enzymes may be related to pathogenesis of this glomerulopathy.
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PMID:Activities of lysosomal enzymes in isolated glomeruli. Alterations in experimental nephrosis. 732 25

We describe an 8-year-old boy who presented with steroid-resistant nephrotic syndrome (SRNS) associated with X-linked ichthyosis (XLI). At birth, the patient exhibited scaly skin, cryptorchidism, and steroid sulfatase (STS) deficiency. DNA analysis showed deletion of exons 1-10 of the STS gene. Proteinuria developed at 6 years and was resistant to steroid therapy. Kidney biopsy findings prior to steroid therapy were compatible with minimal change nephrotic syndrome. By immunofluorescence, glomerular basement membranes exhibited diffuse linear staining for the alpha5 chain of collagen IV, making X-linked Alport syndrome an unlikely explanation for the association of SRNS and ichthyosis. Despite immunosuppressive therapy together with oral prednisolone, no clinical response was achieved. He rapidly reached end-stage renal failure and finally underwent renal transplantation. We propose that SRNS should be considered as one of the highly variable phenotypes associated with XLI.
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PMID:End-stage renal failure in a child with X-linked ichthyosis. 1264 29

Paracrine signaling between podocytes and glomerular endothelial cells through vascular endothelial growth factor A (VEGFA) maintains a functional glomerular filtration barrier. Heparan sulfate proteoglycans (HSPGs), located on the cell surface or in the extracellular matrix, bind signaling molecules such as VEGFA and affect their local concentrations, but whether modulation of these moieties promotes normal crosstalk between podocytes and endothelial cells is unknown. Here, we found that the transcription factor Wilms' Tumor 1 (WT1) modulates VEGFA and FGF2 signaling by increasing the expression of the 6-O-endosulfatases Sulf1 and Sulf2, which remodel the heparan sulfate 6-O-sulfation pattern in the extracellular matrix. Mice deficient in both Sulf1 and Sulf2 developed age-dependent proteinuria as a result of ultrastructural abnormalities in podocytes and endothelial cells, a phenotype similar to that observed in children with WT1 mutations and in Wt1(+/-) mice. These kidney defects associated with a decreased distribution of VEGFA in the glomerular basement membrane and on endothelial cells. Collectively, these data suggest that WT1-dependent sulfatase expression plays a critical role in maintaining the glomerular filtration barrier by modulating the bioavailability of growth factors, thereby promoting normal crosstalk between podocytes and endothelial cells.
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PMID:WT1-dependent sulfatase expression maintains the normal glomerular filtration barrier. 2171 93

Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced renal complications and mechanisms to facilitate readministration of ERT in these patients remain unexplored. This work identifies a new antigen responsible for secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB [rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB titer and dramatically improved clinical manifestations. However, 16 months later, the patient suddenly developed nephrotic syndrome resistant to steroid therapy 1 week after orthopedic surgery. Examination of the kidney biopsy specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN. Double immunofluorescence staining showed that subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted from the patient's biopsy specimen reacted specifically with rhASB. On discontinuation of ERT, proteinuria progressively decreased, but the patient's clinical condition markedly deteriorated. Induction of tolerance to rhASB was initiated by coadministration of low-dose corticosteroids, rituximab, intravenous Igs, and oral methotrexate. ERT was resumed 8 weeks after starting immunosuppressive therapy without inducing a rebound of antibody titer or an increase in proteinuria. We conclude that the allo-immune response to the recombinant rhASB caused the nephropathy. Considering the critical requirement for ERT in patients with such enzyme deficiencies, immune tolerance induction should be advocated in the patients with allo-immune MN.
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PMID:Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy. 2426 93

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.
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PMID:Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction. 3133 40