Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional renal mass

Although studies in partially nephrectomized rats have identified a progressive nephropathy that is altered by dietary restriction of phosphorus intake, the response of dogs to similar perturbations has not been established. Functional renal mass was reduced by 15/16 in dogs to determine its long-term effects on renal function and to evaluate the effects of two levels of dietary mineral (calcium and phosphorus) intake (0.44% phosphorus/0.57% calcium versus 1.50% phosphorus/1.91% calcium). Following a 3-month stabilization period, dogs were fed either the lower mineral diet (group 1, N = 12) or the higher mineral diet (group 2, N = 12) for 24 months. Loss of renal function with the passage of time was observed in 10 of 12 dogs maintained on the higher mineral diet, with an average decrease in exogenous creatinine clearance of 11.1 +/- 6.3%/month, leading to a survival rate of 33% in this group. Restriction of dietary mineral intake slowed (P less than 0.05) the rate of decline of exogenous creatinine clearance in group 1 to 2.6 +/- 1.1%/month and improved 24-month survival to 75% (P less than 0.01). Deterioration of renal function was associated with renal calcium accumulation and histologic evidence of nephrocalcinosis, tubular atrophy and dilatation, and interstitial fibrosis. These events were more readily apparent in female than in male dogs. A role for glomerulosclerosis was not apparent, and neither glomerular pathology nor glomerular volume was related to the observed decrements in renal function.