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Protein Intake and Diabetic Kidney Disease
Protein Intake and Diabetic Kidney Disease
Robert C. Stanton
Joslin Diabetes Center
Low Protein Protects in Renal Ablation Model
Low Protein Protects in Renal Ablation Model
Hostetter et al, AJP, 1981; 241:F85
24% Protein Diet
6% Protein Diet
Right Nephrectomy and
Infarction of about 5/6th of the left
kidney
High Protein Intake is Bad for Kidney Function
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 DietProposed Paleolithic DietP
rote
in I
ntak
e
TIME -Months
MastodonSabre-toothed
TigerChateaubriand
for 2
Vegetables
Whole grains
http://paleodiet.com/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
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
Low Protein Diets and ACE Inhibitors/ARBs
Slow Progression of Kidney Disease by Lowering Glomerular Pressures
MAYBE
Protein Intake and Kidney Disease
Protein Intake and Kidney Disease
• Do low protein diets slow progression of kidney disease?
Protein Intake Affects Progression
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.
High Protein Intake Apparently Increased Renal Decline in Women with Mild Renal
Impairment but not Normal Renal Function
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 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
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
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
Higher Dietary Fat Correlates with Microalbuminuria whereas Higher Protein Correlates with Lower Urine
Albumin Levels
How About Very Low Protein Diets
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?
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 DiseaseHigh Protein Diets and
Cardiovascular Disease
It has been speculated that high protein diets worsen cardiovascular
disease
High Protein Diets Improve CV Outcomes in Women
High Protein Diets Improve CV Outcomes in Women
Hu et al Am J Clin Nutr, 1999, 70:221
Protein Excretion and Kidney Disease
Protein Excretion and Kidney Disease
Urine Protein Excretion (even in the microalbuminuric range) is strongly
positively associated with cardiovascular disease
Borch-Johnsen et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.
6
5
4
3
2
1
0Female Male
Relative risk of IHD
Normoalbuminuria
Microalbuminuria
10-y follow-up, n = 2,085
General Population
Microalbuminuria And Ischemic Heart Disease Risk
Microalbuminuria And Ischemic Heart Disease Risk
Miettinen H et al. Stroke. 1996;27:2033-2039.
Survival
<150 mg/L >300 mg/L150-300 mg/LUrinary protein
All-cause mortality
Months
CVD mortality
Months
A: B: C:
1
0.6
0.5
0.4
0
0.7
0.8
0.9
30 40 50 60 70 80 9020100
A
B
C
Overall <0.001A vs B <0.001A vs C <0.001B vs C <0.001
030 405060 70 80 9020100
A
B
C
1
0.6
0.5
0.4
0.7
0.8
0.9
Overall <0.001A vs B 0.013A vs C <0.001B vs C <0.001
Effect of Proteinuria on All-Cause and CVD Mortality in Patients With
Type 2 Diabetes
Effect of Proteinuria on All-Cause and CVD Mortality in Patients With
Type 2 Diabetes
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.
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
Protein Intake and Kidney Disease
Does the source or type of protein affect outcomes?
Vegetable Protein Appears to be be non-deleterious.
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
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.
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
CARI Guidelines Do Not Recommend Low Protein Diets
CARI Guidelines Do Not Recommend Low Protein Diets
Summary 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.
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