Experimental Membranous Glomerulonephritis

Cattran, Dan; Chodirker, William B.

doi:10.1159/000182656

Nephron

1982

DOI: 10.1159/000182656

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Experimental Membranous Glomerulonephritis

Dan Cattran¹,

William B. Chodirker²

Abstract: Active Heymann’s nephritis was induced in Wistar rats by a single injection of human renal tubular epithelial antigen (FXIA) and the animals were followed for 1 year. Correlations were made between circulating anti-FXIA antibody, circulating immune complexes (CIC) and pathology. The disease progressed pathologically through all stages of membranous nephropathy associated with a high level of free antibody but without significant detectable CIC, suggesting that the dominant disease mechanism may be the reaction… Show more

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1983

1993

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Cited by 5 publications

References 11 publications

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Variability in the renal clearance of cephalexin in experimental renal failure

Maiza

Daley‐Yates

1993

Journal of Pharmacokinetics and Biopharmaceutics

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This study forms a part of an investigation into the extent to which the type of renal damage influences the renal clearance of drugs. We have already demonstrated an effect of different types of experimental renal failure (ERF) on the renal clearance of two cations: cimetidine, a drug that is filtered and secreted by the nephron, and lithium, which is filtered and reabsorbed by more than one segment of the nephron. In this report the renal clearance of cephalexin (CLCEX) is investigated, a drug that has a different mode of renal elimination, since it is filtered, secreted, and reabsorbed by the proximal tubules. The aim was to extend our earlier studies to an organic anion, and to provide an opportunity to evaluate the feasibility of using the renal clearance of N-1-methylnicotinamide (NMN) to predict the renal clearance of anionic drugs in renal failure. Different models of site-specific 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 antibodies). Glomerular function (GFR) was assessed by the clearance of inulin (CLNULIN), and tubular function was assessed by the clearance of endogenous NMN (CLNMN). OUr results show that even if the models of ERF used were not absolutely site-specific, glomerular function and tubular function did not decrease to the same extent in the different ERF. Therefore, glomerulo-tubular imbalance existed, which is incompatible with the "intact nephron hypothesis," i.e., the site of the damage along the nephron and not only the degree of renal dysfunction, is a potential source of variability in the clearance of certain drugs. The renal clearance of cephalexin was estimated more accurately by CLNMN than GFR (r = 0.90). We conclude that the clearance of the endogenous cation NMN can be used to predict the renal clearance of drugs that are not only filtered by the glomeruli but also secreted and/or reabsorbed by the proximal tubules, and in the limited examples investigated appears to apply to both anionic and cationic compounds. In this respect the GFR alone was not an adequate parameter for the prediction of the renal clearance of such drugs.

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Variability in the renal clearance of cephalexin in experimental renal failure

Maiza

Daley‐Yates

1993

Journal of Pharmacokinetics and Biopharmaceutics

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Prediction of the renal clearance of cimetidine using endogenousN-1-methylnicotinamide

Maiza

Daley‐Yates

1991

Journal of Pharmacokinetics and Biopharmaceutics

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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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Alteration of glomerular anionic sites by the development of subepithelial deposits in experimental glomerulonephritis in the rat

Suzuki

Maesawa

Matsui

et al. 1983

Virchows Archiv B Cell Pathol

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Experimental Membranous Glomerulonephritis

Cited by 5 publications

References 11 publications

Variability in the renal clearance of cephalexin in experimental renal failure

Variability in the renal clearance of cephalexin in experimental renal failure

Prediction of the renal clearance of cimetidine using endogenousN-1-methylnicotinamide

Alteration of glomerular anionic sites by the development of subepithelial deposits in experimental glomerulonephritis in the rat

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