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)

To assess whether urinary N-acetyl-beta-D-glucosaminidase (NAG) could be used as a predictor of diabetic nephropathy, renal tubular enzymes such as NAG and gamma-glutamyl transpeptidase (gamma GTP), albumin, total protein and beta 2-microglobulin (BMG) in urine and/or serum were measured in various stages of diabetic nephropathy. As a predictor of diabetic nephropathy, urinary NAG was the most useful indicator among of them. Urinary gamma GTP had no clinical benefit on early detection of diabetic nephropathy although in cis-platin induced nephrotoxicity both urinary gamma GTP and NAG increased in parallel. Increase of urinary NAG appeared in diabetic patients prior to clinical proteinuria. With appearance of proteinuria, urinary NAG more increased. Urinary NAG correlated significantly with HbAlc and BMG in serum (sBMG). It is therefore needed for clinical application of urinary NAG as a predictor of diabetic nephropathy that control states of blood glucose in the patients should be considered. However, the results of sequential measurements of urinary NAG, sBMG and HbAlc in 78 diabetic patients for 18-month period showed that only urinary NAG was a responsible factor for elevation of sBMG known as an indicator of deterioration of renal function. These results indicate that renal tubular damage may already exist in early-stage of diabetic nephropathy, and that increase of urinary NAG activity is a useful predictor of diabetic nephropathy.
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PMID:[Clinical evaluation of N-acetyl-beta-D-glucosaminidase on prediction of diabetic nephropathy]. 135 Jul 71

The problem of accompanying tubular lesions in nephrotic syndrome (NS) is not yet sufficiently clarified. The tubular changes were studied by the urine excretion of sensitive markers: beta 2-microglobulin (beta 2m), alaninaminopeptidase (AAP) and gammaglutamyltranspeptidase (gamma GTP). Beta 2m was determined by ELISA method and AAP and gamma GTP--electrophoretically. 75 patients were examined--37 patients with idiopathic nephrotic syndrome (INS), 27 patients with membranous glomerulonephritis (MGN), 11 patients with membranous-proliferative glomerulonephritis (MPGN). The most sensitive index AAP was elevated in the urine of 97,4% of the patients with nephrotic syndrome, beta 2m was elevated in 64,3% and gamma GTP--in 46,2% of the patients. There is a positive correlation between the excretion of APP and the quantity of proteinuria (r = 0,73, p less than 0,001). The comparison of the results of the patients with and without nephrotic syndrome established that in the patients with idiopathic nephrotic syndrome as well as in the patients with membranous glomerulonephritis the presence of nephrotic syndrome determines the higher excretion of AAP (p less than 0,02). The presence of nephrotic syndrome increases the frequency and the severity of the tubular impairment in glomerulonephritis. The tubular impairment is independent of the histologic type but is in positive correlation with the proteinuria.
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PMID:[Tubular lesions in the nephrotic syndrome]. 257 94

The Rho small G protein family members regulate various actin cytoskeleton-dependent cell functions. The Rho GDI (GDP dissociation inhibitor) family, consisting of Rho GDIalpha, -beta, and -gamma, is a regulator that keeps the Rho family members in the cytosol as the GDP-bound inactive form and translocates the GDP-bound form from the membranes to the cytosol after the GTP-bound form accomplishes their functions. Rho GDIalpha is ubiquitously expressed in mouse tissues and shows GDI activity on all the Rho family members in vitro. We have generated mice lacking Rho GDIalpha by homologous recombination to clarify its in vivo function. Rho GDIalpha -/- mice showed several abnormal phenotypes. Firstly, Rho GDIalpha -/- mice were initially viable but developed massive proteinuria mimicking nephrotic syndrome, leading to death due to renal failure within a year. Histologically, degeneration of tubular epithelial cells and dilatation of distal and collecting tubules were readily detected in the kidneys. Secondly, Rho GDIalpha -/- male mice were infertile and showed impaired spermatogenesis with vacuolar degeneration of seminiferous tubules in their testes. Thirdly, Rho GDIalpha -/- embryos derived from Rho GDIalpha -/- female mice were defective in the postimplantation development. In addition, these morphological and functional abnormalities showed age-dependent progression. These results suggest that the signaling pathways of the Rho family members regulated by Rho GDIalpha play important roles in maintaining the structure and physiological function of at least kidneys and reproductive systems in adult mice.
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PMID:Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. 1049 91

To date, no specific treatment is established in mesangial proliferative glomerulonephritis in humans. Specific stimulation of soluble guanylyl cyclase (sGC), an enzyme catalyzing the synthesis of cGMP from GTP, can be achieved by the novel pyrazolopyridine derivative BAY 41-2272. The effect of sGC stimulation via BAY 41-2272 on mesangial proliferation was assessed in vivo using a mesangial proliferative glomerulonephritis model in rats (anti-Thy1 model). Renal biopsies, as well as glomerular isolates, urine samples, and blood samples were compared in BAY 41-2272- and placebo-treated groups during anti-Thy1 nephritis. The sGC beta(1)-subunit is upregulated during anti-Thy1 nephritis and mainly confined to mesangial areas by immunohistochemistry. Specific therapeutic sGC stimulation during anti-Thy1 nephritis in vivo was achieved via BAY 41-2272 treatment as demonstrated by increased glomerular cGMP levels causing inhibition of mesangial proliferation, glomerular matrix accumulation, and proteinuria compared with placebo-treated animals. sGC is tightly regulated in glomeruli during experimental glomerulonephritis. Considering its beneficial antiproliferative, antifibrotic, and antiproteinuric effect in experimental glomerulonephritis, the therapeutic stimulation of sGC could become a promising future goal in mesangial proliferative glomerulonephritis in humans.
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PMID:Stimulation of soluble guanylyl cyclase inhibits mesangial cell proliferation and matrix accumulation in experimental glomerulonephritis. 1556 76

Obesity hypertension and metabolic syndrome have become major public health concerns. Nowadays, aldosterone is recognized as an important mediator of cardiovascular and renal damage. In the kidney, aldosterone injures glomerular visceral epithelial cells (podocytes), the final filtration barrier to plasma macromolecules, leading to proteinuria and glomerulosclerosis. Mineralocorticoid receptor (MR) antagonists effectively ameliorate proteinuria in patients or in animal models of hypertension, diabetes mellitus and chronic kidney disease (CKD), as well as in patients who experience 'aldosterone breakthrough.' Recently, clinical and experimental studies have shown that plasma aldosterone concentration is associated with obesity hypertension and metabolic syndrome. We showed that spontaneously hypertensive rats (SHR)/cp, an experimental model of obesity hypertension and metabolic syndrome, are prone to glomerular podocyte injury, proteinuria and left ventricular diastolic dysfunction, especially when the animals are fed a high-salt diet. Inappropriate activation of the aldosterone/MR system underlies the renal and cardiac injuries. Adipocyte-derived aldosterone-releasing factors (ARFs), although still unidentified, may account for aldosterone excess and the resultant target organ complication in SHR/cp. On the other hand, recent studies have shown that MR activation triggers target organ disease even in normal or low aldosterone states. We identified a small GTP (guanosine triphosphate)-binding protein, Rac1, as a novel activator of MR, and showed that this ligand-independent MR activation by Rac1 contributes to the nephropathy of several CKD models. We expect that ARFs and Rac1 can be novel therapeutic targets for metabolic syndrome and CKD. Future large-scale clinical trials are awaited to prove the efficacy of MR blockade in patients with obesity hypertension and metabolic syndrome.
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PMID:Mineralocorticoid receptor activation in obesity hypertension. 1952 18

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive renal function decline and affects millions of people. In a recent study, 30% of SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different genes. Here, using homozygosity mapping and whole-exome sequencing, we identified recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2, and KANK4 in individuals with nephrotic syndrome. In an independent functional genetic screen of Drosophila cardiac nephrocytes, which are equivalents of mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is essential for nephrocyte function. RNAi-mediated knockdown of dKank in nephrocytes disrupted slit diaphragm filtration structures and lacuna channel structures. In rats, KANK1, KANK2, and KANK4 all localized to podocytes in glomeruli, and KANK1 partially colocalized with synaptopodin. Knockdown of kank2 in zebrafish recapitulated a nephrotic syndrome phenotype, resulting in proteinuria and podocyte foot process effacement. In rat glomeruli and cultured human podocytes, KANK2 interacted with ARHGDIA, a known regulator of RHO GTPases in podocytes that is dysfunctional in some types of nephrotic syndrome. Knockdown of KANK2 in cultured podocytes increased active GTP-bound RHOA and decreased migration. Together, these data suggest that KANK family genes play evolutionarily conserved roles in podocyte function, likely through regulating RHO GTPase signaling.
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PMID:KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. 2600 15