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)

A significant reduction of renal mass results in proteinuria, glomerulosclerosis, and tubulointerstitial injury, culminating in end-stage chronic renal failure (CRF). The accumulation of lipids in the kidney can cause renal disease. Uptake of oxidized lipoproteins via scavenger receptors, reabsorption of filtered protein-bound lipids via the megalin-cubilin complex, and increased glucose load per nephron can promote lipid accumulation in glomerular, tubular, and interstitial cells in CRF. Cellular lipid homeostasis is regulated by lipid influx, synthesis, catabolism, and efflux. We examined lipid-regulatory factors in the remnant kidney of rats 11 wk after nephrectomy (CRF) or sham operation. CRF resulted in azotemia, proteinuria, lipid accumulation in the kidney, upregulation of megalin, cubilin, mediators of lipid influx (scavenger receptor class A and lectin-like oxidized receptor-1), lipid efflux (liver X receptor alpha/beta and ATP-binding cassette transporter), and fatty acid biosynthesis (carbohydrate-response element binding protein, fatty acid synthase, and acetyl-CoA carboxylase). However, factors involved in cholesterol biosynthesis (sterol regulatory element binding protein, 3-hydroxy-3-methylglutaryl coenzyme A reductase, SCAP, Insig-1, and Insig-2) and fatty acid oxidation (peroxisome proliferator-activated receptor, acyl-CoA oxidase, and liver-type fatty acid binding protein) were reduced in the remnant kidney. Thus CRF results in heavy lipid accumulation in the remnant kidney, which is mediated by upregulation of pathways involved in tubular reabsorption of filtered protein-bound lipids, influx of oxidized lipoproteins and synthesis of fatty acids, and downregulation of pathways involved in fatty acid catabolism.
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PMID:Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. 1969 97

Circulating factors have been implicated in the pathogenesis of minimal change disease (MCD), and may have direct effects on cholesterol metabolism. This study investigated the pathogenesis of hypercholesterolemia in an IL-13 overexpression rat model of MCD prior to the onset of proteinuria, so as to establish the direct contribution of IL-13, especially with regard to hepatic cholesterol handling. In this model of MCD, the temporal relationship between hypercholesterolemia and proteinuria was first identified. Plasma proprotein convertase subtilisin/kexin type 9 (Pcsk9) and liver ATP-binding cassette sub-family G member 5 (Abcg5) were measured using ELISA. Liver Ldlr and liver X receptor alpha (Lxra) were quantified with Western blot. Abcg5-mediated cholesterol efflux in IL-13-stimulated rat primary hepatocytes was measured using taurocholate as cholesterol acceptor. The role of Lxra was validated using a luciferase assay in Lxre-luciferase-transfected IL-13-stimulated hepatocytes. IL-13-transfected rats developed hypercholesterolemia prior to proteinuria, with 35% of rats hypercholesterolemic but only 11% proteinuric by Day 20 (P = 0.04). These pre-proteinuric hypercholesterolemic rats showed elevations in total and LDL-cholesterol, but not hypertriglyceridemia or hepatic steatosis. The hypercholesterolemia was associated with increased hepatic Pcsk9 synthesis and enhanced circulating Pcsk9 levels, which correlated strongly with plasma total cholesterol (r = 0.73, P<0.001). The hypercholesterolemia was also contributed by decreased Abcg5 expression and activity, due to reduced Lxra expression. Lxra expression correlated with plasma total cholesterol levels (r = -0.52, P = 0.01), and overexpression of pLxra in rat hepatocytes abrogated the IL-13-mediated down-regulation of Lxre-driven gene expression. In conclusion, we have shown that IL-13 induced changes in hepatic cholesterol handling in a cytokine-induced rat model of MCD, resulting in hypercholesterolemia which can precede the onset of proteinuria.
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PMID:IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease. 3193 20