The program seeks to rest in non-human primate the proposal that protein may be responsible for progressive loss of GFR in chronic renal insufficiency and that a reduced protein diet may be protective. The investigation, initiated 24 months ago, will be conducted in baboons (Papio hamadryas) with 5/8 reduction in renal mass. Two groups, fed either an 8% or a 25% protein diet, will be compared. The diets are isocaloric and equal in fat, sodium, phosphorus, calcium, oligoelement and vitamin content. The following questions are addressed: Does a glomerulopathy develop in baboon after renal mass ablation and, if so, is the rate of progression of renal dysfunction influenced by protein intake? A second aim, to be initiated only after the primary aims are achieved, will assess the effects of angiotensin converting enzyme inhibition on hypertension and progression of renal insufficiency. Serial studies will compare a) Fasting renal hemodynamics: Whereas clearances of inulin, para- aminohippurate, and endogenous creatinine per kg body weight are significantly higher in 25% than in 8% protein fed baboons, do they decrease faster with high than with low protein diet? Dietary intake will be assessed from sodium, potassium and urea nitrogen excretion in 24hr urines; c) Systemic arterial blood pressure: Is progressive renal dysfunction related to differences in arterial blood pressure? Measurements a to c will be obtained every 4 months in awake animals, d) Morphology and ultrastructure of the viable portion of the remnant kidney will be examined every 18 months by light and electronmicroscopy and ultimately, by quantitative morphometrics; The majority of studies that implicate protein in progressive renal disease have been carried out in rodents. This study should provide definitive information on the role of protein and on the potential benefits of a reduced protein intake in renal insufficiency in primates. The results should be directly relevant to humans.
