Protein Intake and Diabetic Kidney Disease

Protein Intake and Diabetic Kidney Disease

Robert C. Stanton

Joslin Diabetes Center

1/Serum Creatinine Plot

1/Serum Creatinine Plot

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

CavemanCaveman

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?

Kidney

GlomerulusGlomerulus

MicropunctureMicropuncture

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

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.

Nurses Health Study Nurses Health Study

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

Protein IntakeProtein Intake

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

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

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

Kidney International 2007; 71:245

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

Following the Tradition Following the Tradition

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.

Conclusion 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).