Protein Intake and Diabetic Kidney Disease

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Protein Intake and Diabetic Kidney Disease

• Robert C. Stanton
• Joslin Diabetes Center

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1/Serum Creatinine Plot
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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 241F85
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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 1982307652-659

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Caveman
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Proposed Paleolithic Diet
Sabre-toothed Tiger
Chateaubriand for 2
Mastodon
Protein Intake
Vegetables Whole grains
TIME -Months
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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
  19961261732
• 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.
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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
• lt0.8 g/kg/day
• lt0.6 g/kg/day
• lt0.3 g/kg/day

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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?

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Kidney
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Glomerulus
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Micropuncture
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Zatz et al, PNAS, 1985 825963
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Zatz et al, PNAS, 1985 825963
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• Micropuncture studies were done between 2-10
  weeks after inducing diabetes
• Pathology was evaluated 11-13 months after
  inducing diabetes

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Zatz et al, JCI, 1986 771925
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Zatz et al, JCI, 1986 771925
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Low Protein Diets and ACE Inhibitors/ARBs Slow
Progression of Kidney Disease by Lowering
Glomerular Pressures

• MAYBE

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Protein Intake and Kidney Disease

• Do low protein diets slow progression of kidney
  disease?

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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.

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Nurses Health Study
Knight et al, Ann Intern Med. 2003138460-467.
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Protein Intake
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High Protein Intake Apparently Increased Renal
Decline in Women with Mild Renal Impairment but
not Normal Renal Function
MAYBE
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Protein Intake and Urinary Albumin Excretion
Rates in the EURODIAB IDDM Complications Study
Diabetologia 40 19971219-1226
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Demographics
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Protein Intake Appears to Adversely Affect
Albumin Excretion Rate Only in Patients with
Hypertension or Poorer Blood Glucose Control
A1cgt6.4
Hypertensive
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Effect of Low Protein Diet Correlates with Blood
Pressure and Glucose Control
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Wheres 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

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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 6750
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Higher Dietary Fat Correlates with
Microalbuminuria whereas Higher Protein
Correlates with Lower Urine Albumin Levels
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How About Very Low Protein Diets
Giordano Kidney International 1982 22401
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Kidney International 2007 71245
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How About Type 2 Diabetes?Moderate Protein Diet
Restriction Improves Things I think?
Pomerleau et al Diabetologia (1993) 36829-834
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Wheres the Beef?
So maybe low protein diets are not beneficial.
But a chronic high protein is clearly
detrimental. Right?
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High Protein Diets and Cardiovascular Disease

• It has been speculated that high protein diets
  worsen cardiovascular disease

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High Protein Diets Improve CV Outcomes in Women
Hu et al Am J Clin Nutr, 1999, 70221
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Protein Excretion and Kidney Disease

• Urine Protein Excretion (even in the
  microalbuminuric range) is strongly positively
  associated with cardiovascular disease

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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. 1999191992-1997.
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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
0.7
B
Survival
0.6
0.6
Overall lt0.001 A vs B 0.013 A vs C lt0.001 B vs
C lt0.001
Overall lt0.001 A vs B lt0.001A vs C lt0.001 B vs
C lt0.001
C
0.5
0.5
C
0.4
0.4
0
0
30
40
50
60
70
80
90
20
10
0
Months
Months
B
C
Urinary protein
A
lt150 mg/L
gt300 mg/L
150-300 mg/L
Miettinen H et al. Stroke. 1996272033-2039.
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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.
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Protein Intake and Kidney Disease

• Does the source or type of protein affect
  outcomes?

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Vegetable Protein Appears to be be
non-deleterious.
Knight et al, Ann Intern Med. 2003138460-467.
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Fish Protein Reduces Progression to
Microalbuminuria in Type 1 Diabetic Patients
Mollsten et al Diabetes Care, 2001, 24805
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Effects of soy protein on renal function and
proteinuria in patients with type 2 diabetes.
Anderson et al Am J Clin Nutr.1998, 681347S.
NO CHANGE
Soy diet worsened proteinuria
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Following the Tradition
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CARI Guidelines Do Not Recommend Low Protein Diets
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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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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).