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)

We investigated the influence of the type rather than the degree of renal insufficiency on the renal clearance of drugs. Different models of site specific experimental renal failure (ERF) have been developed in the rat; proximal tubular necrosis, induced by cisplatin; papillary necrosis, induced by 2-bromoethylamine, and glomerulonephritis, induced by sodium aurothiomalate or by antiglomerular basement membrane antibody. Several parameters of kidney function were assessed: the clearance of inulin, PAH, and endogenous N-1-methylnicotinamide (NMN). Plasma BUN and creatinine concentrations, and the presence of proteinuria and glucosuria were also measured. Our results showed a nonparallel decrease in glomerular filtration rate (GFR) and tubular secretion as measured by the secretory clearance of endogenous NMN or by the secretory clearance of p-aminohippuric acid (PAH), that is incompatible with the "intact nephron hypothesis." As a result, the renal clearance of cimetidine, a drug eliminated mainly by renal secretion, correlated better with the renal clearance of endogenous NMN than with the GFR. We conclude that (i) our models of ERF demonstrated the existence of glomerulo-tubular imbalance that is contrary to expectations based on the intact nephron hypothesis; (ii) the type of the renal disease has a direct influence on the renal clearance of cimetidine; (iii) the clearance of endogenous NMN may be a valuable noninvasive test for assessing renal tubular secretion which could be useful in predicting the clearance of drugs eliminated predominantly by tubular secretion.
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PMID:Prediction of the renal clearance of cimetidine using endogenous N-1-methylnicotinamide. 182 32

Free fatty acid-bound albumin (FFA-albumin)-related oxidative stress is involved in the pathogenesis of proximal tubular cell (PTC) damage and subsequent renal dysfunction in patients with refractory proteinuria. Nicotinamide adenine dinucleotide (NAD) metabolism has recently been focused on as a novel therapeutic target for several modern diseases, including diabetes. This study was designed to identify a novel molecule in NAD metabolism to protect PTCs from lipotoxicity-related oxidative stress. Among 19 candidate enzymes involved in mammalian NAD metabolism, the mRNA expression level of nicotinamide n-methyltransferase (NNMT) was significantly increased in both the kidneys of FFA-albumin-overloaded mice and cultured PTCs stimulated with palmitate-albumin. Knockdown of NNMT exacerbated palmitate-albumin-induced cell death in cultured PTCs, whereas overexpression of NNMT inhibited it. Intracellular concentration of 1-Methylnicotinamide (1-MNA), a metabolite of NNMT, increased and decreased in cultured NNMT-overexpressing and -knockdown PTCs, respectively. Treatment with 1-MNA inhibited palmitate-albumin-induced mitochondrial reactive oxygen species generation and cell death in cultured PTCs. Furthermore, oral administration of 1-MNA ameliorated oxidative stress, apoptosis, necrosis, inflammation, and fibrosis in the kidneys of FFA-albumin-overloaded mice. In conclusion, NNMT-derived 1-MNA can reduce lipotoxicity-mediated oxidative stress and cell damage in PTCs. Supplementation of 1-MNA may have potential as a new therapy in patients with refractory proteinuria.
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PMID:1-Methylnicotinamide ameliorates lipotoxicity-induced oxidative stress and cell death in kidney proximal tubular cells. 2648 66