Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats.

Abstract

Recent studies indicate that parathyroidectomy (PTX) prevents the progression of kidney damage due to high protein diet in the subtotal nephrectomized rat model of chronic renal failure. Associated with this protection, the difference in the renal "compensatory" growth induced by high (HPr) as compared to normal protein diet (NPr) is completely abolished by PTX. To understand the physiological mechanism responsible for this protection, the changes in both circulating level and kidney content of IGF-1, a growth factor capable of influencing renal "compensatory" growth, was analyzed after unilateral nephrectomy (UNX). In UNX rats, HPr as compared to NPr diet given for five days significantly increased the kidney/body weight ratio (0.48 +/- 0.01%, N = 11 vs. 0.44 +/- 0.01%, N = 11, P < 0.005) and the plasma level of IGF-1 (365 +/- 10 ng/ml vs. 306 +/- 10 ng/ml, P < 0.001). In UNX rats fed HPr, PTX completely abolished the renal "compensatory" growth (0.38 +/- 0.02%, N = 7, P < 0.001) and the increased plasma level of IGF-1 (246 +/- 14 ng/ml, N = 7, P < 0.001). In PTX-UNX rats treated with physiological doses of 1,25-dihydroxyvitamin D3 which nearly normalized the calcemia, the renal growth and the increased plasma level of IGF-1 induced by HPr were restored towards those recorded in SHAM-UNX rats fed the HPr diet. Similar effects were observed in PTX-UNX rats in which the plasma calcium concentration was increased by the chronic administration of a retinoid derivative, used as an agent where the calcemic effect is essentially mediated by a stimulation of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)