POTENTIAL ROLE OF IGF-1 IN PARATHYROID HORMONE-RELATED RENAL GROWTH INDUCED BY HIGH-PROTEIN DIET IN UNINEPHRECTOMIZED RATS

Recent studies indicate that parathyroidectomy (PTX) prevents the prog ression of kidney damage due to high protein diet in the subtotal neph rectomized rat model of chronic renal failure. Associated with this pr otection, the difference in the renal ''Compensatory'' growth induced by high (HPr) as compared to normal protein diet (NPr) is completely a bolished 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 ''comp ensatory'' growth, was analyzed after unilateral nephrectomy (UNX). In UNX rats, HPr as compared to NPr diet given for dye days significantl y 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 IGP-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/mr, N = 7, P < 0.001). In PTX-UNX rats treated with physiologica l doses of 1,25-dihydroxyvitamin D-3 which nearly normalized the calce mia, the renal growth and the increased plasma level of IGE-1 induced by HPr were restored towards those recorded in SHAM-UNX rats fed the H Pr diet. Similar effects were observed in PTX-UNX rats in which the pl asma 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. There was a positive significant correlation between the change in kidney growt h in response to UNX and the plasma level of IGF-1 (r = 0.685, P < 0.0 01). The kidney IGF-1 content was affected neither by the protein inta ke nor by the PTH status. In rats with an intact renal mass and fed NP r diet, chronic administration of bovine PTH: did not alter the plasma IGF-1 concentration. In these animals, both the increase of the plasm a IGF-1 lever under HPr diet and the blunting effect of PTX thereon we re similar to the response observed in UNX animals. There was, however , no significant change in the kidney/body weight ratios in response t o HPr diet. In conclusion, the results of the present study provide ev idence that calciotropic hormones such as PTH and 1,25-dihydroxyvitami n D-3 and/or the associated change in extracellular calcium concentrat ion modulate the effect of protein intake on hepatic production of IGF -1. In rats with a reduced renal mass, the elevation in the circulatin g level of IGF-1 is likely responsible for the increased ''compensator y'' growth of remaining nephrons, which is associated with an accelera tion of renal function deterioration induced by high protein diet.