Acute renal failure and fluid retention and kidney damage in copper-deficient rats fed a high-NaCl diet.

The effect of an interaction between Cu status and dietary NaCl level on kidney structure, water balance, and the plasma renin-angiotensin-aldosterone system (RAAS) was examined in 64 male Sprague-Dawley rats (178 gm) fed a copper-supplemented diet (CuS) (10 micrograms Cu per gram) or a copper-deficient diet (CuD) (less than 0.7 micrograms Cu per gram), with (CuSNa, CuDNa) or without 3% NaCl for 42 days. NaCl did not affect growth, fluid retention, or kidney ultrastructure in Cu-supplemented rats. Cu deficiency decreased growth rate and kidney Cu, increased plasma cholesterol concentration, and suppressed plasma RAAS. NaCl increased the magnitude of these changes in Cu-deficient rats. The mortality rate was higher in CuDNa (8/16) than in Cu-deficient (2/16) rats. An acute renal failure syndrome characterized by tissue edema, pleural effusion, and ascites occurred in rats fed CuDNa. Bioelectric impedence analysis indicated that body water content was similar in rats fed CuS, CuSNa, and CuD but was higher in edematous and nonedematous rats fed CuDNa. Transmission electron microscopy indicated that glomeruli from Cu-deficient rats were poorly perfused and often occluded by expanded mesangium and contained numerous lysozome-like bodies. Fusion of podocyte foot processes, derangement of glomerular basement membrane, and hypertrophy and lipid accumulation by glomerular capillary endothelium were present in tissue from rats fed CuDNa. These results indicate that Cu deficiency reduces NaCl tolerance in rats. Ultrastructural changes in kidney tissue and the suppression of RAAS in rats fed CuDNa suggest that the edema and ascites result from acute renal failure and not from increased fluid and electrolyte reabsorption.