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

Right Nephrectomy
and
Infarction of about
5/6th of the left
6% Protein Diet 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

Sabre-toothed Chateaubriand
Mastodon Tiger for 2
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, 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
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

Knight et al, Ann Intern Med. 2003;138:460-467.

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?

• 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?

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
Normoalbuminuria
4 Microalbuminuria

Relative
3
risk of IHD
2

0
Female Male
10-y follow-up, n = 2,085
Borch-Johnsen et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.
 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
0.8 A 0.8 A
B
0.7 B 0.7
Survival 0.6 0.6
Overall <0.001 Overall <0.001
A vs B <0.001 0.5 A vs B 0.013 C
0.5 C
A vs C <0.001 A vs C <0.001
0.4 B vs C <0.001 0.4 B vs C <0.001

0 0
0 10 20 30 40 50 60 70 80 90 0 10 20 30 40 50 60 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
 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).