The program is designed to test the proposal that an excessive intake of protein relative to glomerular filtration rate (GFR) is responsible for progressive loss of GFR in chronic renal insufficiency, and that a reduced protein diet is protective. The investigation will be conducted in awake and in anesthetized non-human primates (baboon, Papio hamadryas) with 6/8 reduction in functional renal mass. Two groups of baboons fed either a reduced (8 percent) or a high (24 percent) protein diet will be compared. The diets will be isocaloric and equal in sodium, phosphorus, calcium, oligoelements and vitamins. The prospective effects of renal ablation and dietary protein manipulation will be ascertained on both renal structure and hemodynamics to answer the following questions: Does a primary glomerulopathy develop in baboons after renal ablation and, if so, is the rate of progression of renal dysfunction influenced by protein intake? The effects of the two protein diets will be assessed by comparing the changes as a function of time in 1) 24-hr urinary protein excretion. Does proteinuria develop and, if so, is it greater and more progressive in high than in low protein fed baboons?; 2) Fasting renal hemodynamics. Are clearances of insulin, para-aminohippurate, and endogenous creatinine increased in high protein fed baboons but do they drop off faster than in low protein fed animals?; 3) Renal hemodynamics reserve. What is the impact of high vs low protein diet on filtration reserve? The latter will be evaluated with atriopeptin lll or ingestion of a high protein meal; 4) Renal morphology (evaluated by light, electron microscopy and morphometrics). Does glomerular mesangial hyperplasia develop after renal ablation and does it progress to glomerular sclerosis and glomerular obsolescence in high protein fed baboons? Does a reduced protein intake prevent development of glomerular sclerosis?; 5) Blood pressure. Is the impact of protein on renal function related to differences in arterial blood pressure? This study in non-human primates should provide unequivoccal evidence of the role of proteins and of the potential benefits of a reduced protein diet on progressive GFR loss in early chronic renal insufficiency. The results should be directly applicable to humans with chronic renal disease.
