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Protein Intake and Diabetic Kidney Disease Robert C. Stanton Joslin Diabetes Center
Low Protein Protects in Renal Ablation Model 24% Protein Diet Right Nephrectomy and Infarction of about 5/6th of the left kidney 6% Protein Diet Hostetter et al, AJP, 1981; 241:F85
High Protein Intake is Bad for Kidney Function • T. Hostetter T.W. Meyer B.M. Brenner • Hostetter, Meyer, and Brenner. • Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. • New England Journal of Medicine 1982:307:652-659
Proposed Paleolithic Diet Sabre-toothed Tiger Chateaubriand for 2 Mastodon Protein Intake Vegetables Whole grains TIME -Months
http://paleodiet.com/ • The stone age diet: Based on in-depth studies of human ecology and the diet of man. Voegtlin, Walter L. (1975). Vantage Press. • An Evolutionary Perspective Enhances Understanding of Human Nutritional Requirements. Eaton, EatonIII, Konner,Shostak. J. Nutrition 1996:126:1732 • Paleolithicnutrition.Aconsiderationofitsnatureandcurrentimplications.Eaton,Konner1985: N.Engl.J.Med.312:283 Protein Intake Estimated at 2-3 grams/kg/day which was estimated to be about 30% of the diet.
Diets Today Contemporary Diet Recommendations: 15-20% of calories from protein often ranging from 0.8-1.4 g/kg/day Low Protein Diets that have been Recommended/Studied <0.8 g/kg/day <0.6 g/kg/day <0.3 g/kg/day
Protein Intake and Kidney Disease • By what mechanisms do changes in protein intake affect progression of kidney disease? • Do low protein diets slow progression of kidney disease? • Does the source or type of protein affect outcomes?
Micropuncture studies were done between 2-10 weeks after inducing diabetes • Pathology was evaluated 11-13 months after inducing diabetes
Low Protein Diets and ACE Inhibitors/ARBs Slow Progression of Kidney Disease by Lowering Glomerular Pressures MAYBE
Protein Intake and Kidney Disease • Do low protein diets slow progression of kidney disease?
Protein Intake Affects Progression • High protein diets in animal models of kidney disease hasten decline in renal function. Low protein diets in animal models preserve kidney function. • High protein diets tend to raise urine protein levels and low protein diets tend to lower urine protein levels. • Urine Protein levels above 1 gm/day are directly correlated with progression of kidney disease. • Hence lowering protein in the diet will slow progression of kidney disease. • Maybe.
Nurses Health Study Knight et al, Ann Intern Med. 2003;138:460-467.
High Protein Intake Apparently Increased Renal Decline in Women with Mild Renal Impairment but not Normal Renal Function MAYBE
Protein Intake and Urinary Albumin Excretion Rates in the EURODIAB IDDM Complications Study Diabetologia 40: 19971219-1226
Protein Intake Appears to Adversely Affect Albumin Excretion Rate Only in Patients with Hypertension or Poorer Blood Glucose Control A1c>6.4% Hypertensive
Effect of Low Protein Diet Correlates with Blood Pressure and Glucose Control
Where’s the Beef? • Correlative Study - not a longitudinal study • The correlation between progression of kidney disease and levels of albumin in the microalbuminuric range is fuzzy. (Unlike the close correlation with cardiovascular disease) • The findings might be interpreted as providing another rationale for blood pressure control and glucose control rather than providing a reason for low protein intake
Microalbuminuria is positively associated with usual dietary saturated fat intake and negatively associated with usual dietary protein intake in people with insulin-dependent diabetes mellitus. Am J Clin Nutr. 1998; 67:50
Higher Dietary Fat Correlates with Microalbuminuria whereas Higher Protein Correlates with Lower Urine Albumin Levels
How About Very Low Protein Diets Giordano Kidney International 1982; 22:401
How About Type 2 Diabetes?Moderate Protein Diet Restriction Improves Things: I think? Pomerleau et al Diabetologia (1993) 36:829-834
Where’s the Beef? So maybe low protein diets are not beneficial. But a chronic high protein is clearly detrimental. Right?
High Protein Diets and Cardiovascular Disease It has been speculated that high protein diets worsen cardiovascular disease
High Protein Diets Improve CV Outcomes in Women Hu et al Am J Clin Nutr, 1999, 70:221
Protein Excretion and Kidney Disease Urine Protein Excretion (even in the microalbuminuric range) is strongly positively associated with cardiovascular disease
Microalbuminuria And Ischemic Heart Disease Risk General Population 6 5 Normoalbuminuria Microalbuminuria 4 Relative risk of IHD 3 2 1 0 Male Female 10-y follow-up, n = 2,085 Borch-Johnsen et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.
0 10 20 30 40 50 60 70 80 90 Effect of Proteinuria on All-Cause and CVD Mortality in Patients With Type 2 Diabetes • All-cause mortality • CVD mortality 1 1 0.9 0.9 A A 0.8 0.8 B 0.7 B 0.7 Survival 0.6 0.6 Overall <0.001 A vs B 0.013 A vs C <0.001 B vs C <0.001 Overall <0.001 A vs B <0.001A vs C <0.001 B vs C <0.001 C 0.5 0.5 C 0.4 0.4 0 0 0 10 20 30 40 50 60 70 80 90 • Months • Months B: C: A: • Urinary protein <150 mg/L • 150-300 mg/L • >300 mg/L Miettinen H et al. Stroke. 1996;27:2033-2039.
Many studies support a connection between urine protein and cardiovascular disease. Whether increased dietary protein adversely affects cardiac outcomes in patients with proteinuria is an open question.
Protein Intake and Kidney Disease Does the source or type of protein affect outcomes?
Vegetable Protein Appears to be be non-deleterious. Knight et al, Ann Intern Med. 2003;138:460-467.
Fish Protein Reduces Progression to Microalbuminuria in Type 1 Diabetic Patients Mollsten et al Diabetes Care, 2001, 24:805
Effects of soy protein on renal function and proteinuria in patients with type 2 diabetes. Anderson et al Am J Clin Nutr.1998, 68:1347S. NO CHANGE Soy diet worsened proteinuria