Hypothyroidism retards progressive glomerulosclerosis in the rat by a reduction in food intake

Abstract

Hypothyroidism diminishes proteinuria and prolongs survival in several immune models of progressive renal failure. In the well-characterized non-immune model of 5/6 nephrectomy we studied the effects of thyroidectomy (Tx) on the development of proteinuria and glomerulosclerosis (GS). Hypothyroidism was confirmed by lower values of thyroxine in Tx rats compared to sham Tx rats at 9 weeks (12.6 +/- 6.7 nmol/l Tx versus 37.7 +/- 10.8 nmol/l sham Tx) and 12 weeks after operation (7.2 +/- 4.9 nmol/l Tx versus 14.4 +/- 4.1 nmol/l sham Tx). Tx resulted in a reduction in mean arterial blood pressure and proteinuria and a lower incidence of GS (4.2 +/- 3.1% Tx versus 17.1 +/- 10.0% sham Tx) 12 weeks after nephrectomy, along with a decrease in food intake (104 +/- 13 g/week Tx versus 138 +/- 10 g/week sham Tx). In the same experiment a third group of sham Tx rats was pair fed to the Tx rats, resulting in values similar to those of Tx rats for proteinuria and the incidence of GS (6.0 +/- 4.9% pair fed sham Tx). Thyroxine levels at 9 and 12 weeks were comparable to those in sham Tx rats fed ad libitum. No association was found between the incidence of GS and glomerular volume. Studies of the inulin clearance in a second set of experiments showed that glomerular filtration rate and renal plasma flow are lower in hypothyroid rats compared to sham Tx rats. We conclude that hypothyroidism has a renal protective effect due to a decrease in food intake resulting in alterations in renal haemodynamics.