Search

Although secondary hyperparathyroidism is a common complication of chronic renal failure, few studies have examined the characteristics of parathyroid hormone (PTH) binding to the kidney or the regulation of the PTH receptor in chronic renal disease. In this study we measured PTH binding to the PTH-1 receptor in renal cortical membranes from normal rats and from rats with experimentally induced chronic renal failure. In normal rats, analysis of saturation binding experiments using 125I PTH-related peptide (chicken, cPTHrP) revealed apparent Kd and Bmax values of 1.16 +/- 0.14 nmol/l and 338 +/- 22.7 fmol/mg, respectively. Three weeks following induction of renal failure there was no change in the affinity of the PTH-1 receptor (Kd = 1.51 +/- 0.24 nmol/l) but the Bmax was reduced by 45% (183 +/- 32.5). In normal rats which had undergone thyroparathyroidectomy, the Kd was unchanged (1.17 +/- 0.09) while the Bmax increased to 459 +/- 31 fmol/mg. We conclude that chronic renal failure is accompanied by a downregulation of renal PTH-1 receptors., (Copyright 2001 S. Karger AG, Basel)

The effect of the angiotensin-converting enzyme inhibitor captopril on clusterin mRNA was examined in partially nephrectomized male rats. Urine protein excretion was measured 3, 7, and 28 days after removal of five sixths of the renal mass. Nephrectomy caused a progressive increase in clusterin mRNA levels in the remnant kidney. Maximal clusterin mRNA levels occurred 7 days after nephrectomy and declined 28 days after nephrectomy. Captopril, 250 mg/ml in drinking water, prevented the injury-induced increase in clusterin mRNA at 7 and 28 days. Captopril had no effect on clusterin in sham-operated rats. As expected, the urine protein excretion increased progressively after nephrectomy, and this was attenuated by administration of captopril in the drinking water. Therefore, clusterin is a marker of renal injury which, along with proteinuria, is modulated by angiotensin-converting enzyme inhibition.

Evidence suggests that transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy. The aim of the present study was to investigate the effect of captopril on the expression of TGF-beta 1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy. Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney. Sham-operated animals were used as controls. RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham surgery. TGF-beta 1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes. Subsequently, TGF-beta 1 mRNA expression continued to increase over the next 2-4 weeks. The upregulation of TGF-beta 1 correlated with the degree of proteinuria. Both the increase in TGF-beta 1 mRNA and proteinuria were abrogated by captopril treatment. In addition, no change in expression of ALK-5 or type II TGF-beta receptors following five-sixths nephrectomy was observed. These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-beta 1 expression and hence matrix production.

The present study demonstrates that the nitric oxide synthase inhibitor, aminoguanidine, can attenuate the proteinuria observed in a predominantly noninflammatory model of chronic renal disease in the rat. These data suggest that nitric oxide synthase may be involved in progressive renal disease.