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- Title
Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats.
- Authors
Caverzasio, Joseph; Rizzoli, Shigematsu R.; Bonjour, Jean-Philippe
- Abstract
Recent studies indicate that parathyroidectamy (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 NFr 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 plusmn; 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 D, 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 SHAMUNX 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. There was a positive significant correlation between the change in kidney growth in response to UNX and the plasma level of IGF-1 (r = 0.685, P < 0.001), The kidney IGF-1 content was affected neither by the protein intake nor by the PTH status. In rats with an intact renal mass and fed NPr diet, chronic administration of bovine PTH did not alter the plasma IGF-1 concentration. In these animals, both the increase of the plasma IGF-l level under HPr diet and the blunting effect of PTX thereon were similar to the response observed in UNX animals. There was, however, no significant change in the kidney/body weight ratios in response to HPr diet. In conclusion, the results of the present study provide evidence that calciotropic hormones such as PTH and 1,25-dihydroxyvitamin D, and/or the associated change in extracellular calcium concentration modulate the effect of protein intake on hepatic production of IGF-1. In rats with a reduced renal mass, the elevation in the circulating level of IGF-1 is likely responsible for the increased ‘compensatory’ growth of remaining nephrons, which is associated with an acceleration of renal function deterioration induced by high protein diet.
- Subjects
PARATHYROID hormone; KIDNEY diseases; IMMUNOGLOBULINS; PROTEINS; CHRONIC kidney failure; NEPHROLOGY
- Publication
Kidney International, 1995, Vol 48, Issue 1, p33
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1995.263