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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK019822-15
Application #
3226556
Study Section
General Medicine B Study Section (GMB)
Project Start
1976-07-01
Project End
1992-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
15
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
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Mele, Alessandra; Cervantes, Jesus Revuelta; Chien, Victor et al. (2014) Single nucleotide polymorphisms at the TNFAIP3/A20 locus and susceptibility/resistance to inflammatory and autoimmune diseases. Adv Exp Med Biol 809:163-83
Lehmann, R; Wagner, J L; Fernandez, L A et al. (1997) Effects of ketamine sedation on glucose clearance, insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas). J Med Primatol 26:312-21
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Bourgoignie, J J (1992) Progression of renal disease: current concepts and therapeutic approaches. Kidney Int Suppl 36:S61-5
Bourgoignie, J J; Gavellas, G; Hwang, K H et al. (1989) Renal function of baboons (Papio hamadryas) with a remnant kidney, and impact of different protein diets. Kidney Int Suppl 27:S86-90