Protein Intake and Diabetic Kidney Disease Robert C. Stanton Joslin Diabetes Center
1/Serum Creatinine Plot
Low Protein Protects in Renal Ablation Model 24% Protein Diet 6% Protein Diet Right Nephrectomy and Infarction of about 5/6th of the left kidney 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
Caveman
Proposed Paleolithic Diet Proposed Paleolithic Diet Protein Intake Vegetables Whole grains Mastodon Sabre-toothed Tiger Chateaubriand for 2 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, Eaton III, Konner, Shostak. J. Nutrition 1996:126:1732 Paleolithic nutrition. A consideration of its nature and current implications. Eaton, Konner 1985: 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 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?
Kidney
Glomerulus
Micropuncture
Zatz et al, PNAS, 1985; 82:5963
Zatz et al, PNAS, 1985; 82:5963
Micropuncture studies were done between 2-10 weeks after inducing diabetes Pathology was evaluated 11-13 months after inducing diabetes
Zatz et al, JCI, 1986; 77:1925
Zatz et al, JCI, 1986; 77:1925
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 Nurses Health Study Knight et al, Ann Intern Med. 2003;138:460-467.
Protein Intake Protein Intake
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
Demographics
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? 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
Kidney International 2007; 71:245
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? 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 6 General Population 5 4 Normoalbuminuria Microalbuminuria Relative risk of IHD 3 2 1 0 10-y follow-up, n = 2,085 Female Male Borch-Johnsen et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.
Survival Effect of Proteinuria on All-Cause and CVD Mortality in Patients With 1 0.9 0.8 0.7 0.6 0.5 0.4 Type 2 Diabetes All-cause mortality Overall <0.001 A vs B A vs C <0.001 <0.001 B vs C <0.001 A B C 1 0.9 0.8 0.7 0.6 0.5 0.4 CVD mortality Overall <0.001 A vs B 0.013 A vs C <0.001 B vs C <0.001 A B C 0 0 10 20 30 40 50 60 70 80 90 0 0 10 20 30 405060 70 80 90 Months Months Urinary protein A: <150 mg/l B: 150-300 mg/l C: >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
Following the Tradition Following the Tradition
CARI Guidelines Do Not Recommend Low Protein Diets
Summary Studies in patients with type 1 diabetes and kidney disease are very variable. There are almost no studies on patients with type 2 diabetes and kidney disease. Fish protein and vegetable proteins may be better than animal proteins - possibly for reasons other than protein content. There may be value in very low protein diets which may be due to other factors. High protein intake likely should be avoided. But how high is high? Protein intake and cardiovascular disease relationship is another variable that is unclear There also may be ethnic differences in response to protein intake.
Conclusion At this time, it appears that no special recommendations for protein inake in patients with diabetic kidney disease should be made other than avoiding high protein intake (whatever that is).