Protein Intake and Diabetic

Kidney Disease

RobertC.Stanton
JoslinDiabetesCenter

1/Serum Creatinine
Plot

Low Protein Protects in Renal

Ablation Model
24%ProteinDiet

6%ProteinDiet

Hostetteretal,AJP,1981;241:F85

RightNephrectomy
and

Infarctionofabout
5/6thoftheleft
kidney

High Protein Intake is Bad for

Kidney Function

T.HostetterT.W.MeyerB.M.Brenner

Hostetter,Meyer,andBrenner.
Dietaryproteinintakeandtheprogressivenatureofkidneydisease:the
roleofhemodynamicallymediatedglomerularinjuryinthepathogenesis
ofprogressiveglomerularsclerosisinaging,renalablation,andintrinsic
renaldisease.
NewEnglandJournalofMedicine1982:307:652659

Caveman

ProteinIntake

Proposed Paleolithic Diet

Mastodon

Sabretoothed
Tiger

Vegetables
Wholegrains
TIMEMonths

Chateaubriand
for2

http://paleodiet.com/

Thestoneagediet:Basedonindepthstudiesofhumanecologyand
thedietofman.Voegtlin,WalterL.(1975).VantagePress.

AnEvolutionaryPerspectiveEnhancesUnderstandingofHumanNutritional
Requirements.Eaton,EatonIII,Konner,Shostak.J.Nutrition1996:126:1732

Paleolithic nutrition. A consideration of its nature and current

implications. Eaton, Konner 1985: N. Engl. J. Med. 312: 283

ProteinIntakeEstimatedat23grams/kg/daywhich
wasestimatedtobeabout30%ofthediet.

Diets Today
ContemporaryDietRecommendations:

1520%ofcaloriesfromproteinoftenrangingfrom
0.81.4g/kg/day
LowProteinDietsthathavebeenRecommended/Studied
<0.8g/kg/day
<0.6g/kg/day
<0.3g/kg/day

Protein Intake and

Kidney Disease
Bywhatmechanismsdochangesinprotein
intakeaffectprogressionofkidneydisease?
Dolowproteindietsslowprogressionof
kidneydisease?
Doesthesourceortypeofproteinaffect
outcomes?

Kidney

Glomerulus

Micropuncture

Zatzetal,PNAS,1985;82:5963

Zatzetal,PNAS,1985;82:5963

 Micropuncturestudiesweredonebetween
210weeksafterinducingdiabetes
Pathologywasevaluated1113months
afterinducingdiabetes

Zatzetal,JCI,1986;77:1925

Zatzetal,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

Dolowproteindietsslowprogressionof
kidneydisease?

Protein Intake Affects

Progression
Highproteindietsinanimalmodelsofkidney
diseasehastendeclineinrenalfunction.Lowprotein
dietsinanimalmodelspreservekidneyfunction.
Highproteindietstendtoraiseurineproteinlevels
andlowproteindietstendtolowerurineprotein
levels.
UrineProteinlevelsabove1gm/dayaredirectly
correlatedwithprogressionofkidneydisease.
Henceloweringproteininthedietwillslow
progressionofkidneydisease.
Maybe.

Nurses Health Study

Knightetal,AnnInternMed.2003;138:460467.

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

EffectofLowProteinDietCorrelateswithBlood
PressureandGlucoseControl

Wheres the Beef?

CorrelativeStudynotalongitudinalstudy
Thecorrelationbetweenprogressionofkidney
diseaseandlevelsofalbumininthe
microalbuminuricrangeisfuzzy.(Unlikethe
closecorrelationwithcardiovasculardisease)
Thefindingsmightbeinterpretedasproviding
anotherrationaleforbloodpressurecontroland
glucosecontrolratherthanprovidingareasonfor
lowproteinintake

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

KidneyInternational2007;71:245

How About Type 2 Diabetes?

Moderate Protein Diet Restriction
Improves Things: I think?

PomerleauetalDiabetologia(1993)36:829834

Wheres the Beef?

Somaybelowproteindiets
arenotbeneficial.Buta
chronichighproteinis
clearlydetrimental.
Right?

High Protein Diets and

Cardiovascular Disease

Ithasbeenspeculatedthathigh
proteindietsworsencardiovascular
disease

High Protein Diets Improve CV

Outcomes in Women

HuetalAmJClinNutr,1999,70:221

Protein Excretion and Kidney

Disease

UrineProteinExcretion(eveninthe
microalbuminuricrange)isstrongly
positivelyassociatedwith
cardiovasculardisease

Microalbuminuria And
Ischemic Heart Disease Risk
6
5
4

General Population

Normoalbuminuria
Microalbuminuria

Relative 3
risk of IHD
2
1
0

Female

10-y follow-up, n = 2,085

Borch-Johnsen et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.

Male

Effect of Proteinuria on All-Cause

and CVD Mortality in Patients With
Type 2 Diabetes
All-cause mortality

CVD mortality

0.9

0.9

0.8

0.8

0.7

0.7

Survival 0.6
0.5
0.4
0

Overall
A vs B
A vs C
B vs C

0.6

<0.001
<0.001
<0.001
<0.001

Miettinen H et al. Stroke. 1996;27:2033-2039.

Overall <0.001
A vs B
0.013
A vs C <0.001
B vs C <0.001

0.5
0.4

0 10 20 30 40 50 60 70 80 90

Months
Urinary protein A:<150 mg/L

A
B

0 10 20 30 40 50 60 70 80 90

B:
150-300 mg/L

Months
C:>300 mg/L

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

Doesthesourceortypeofproteinaffect
outcomes?

Vegetable Protein Appears to be

be non-deleterious.

Knightetal,AnnInternMed.2003;138:460467.

Fish Protein Reduces Progression to

Microalbuminuria in Type 1 Diabetic
Patients

MollstenetalDiabetesCare,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.
NOCHANGE

Soydietworsenedproteinuria

Following the Tradition

CARI Guidelines Do Not

Recommend Low Protein Diets

Summary
Studiesinpatientswithtype1diabetesandkidneydiseasearevery
variable.Therearealmostnostudiesonpatientswithtype2diabetes
andkidneydisease.

Fishproteinandvegetableproteinsmaybebetterthananimalproteins
possiblyforreasonsotherthanproteincontent.
Theremaybevalueinverylowproteindietswhichmaybedueto
otherfactors.

Highproteinintakelikelyshouldbeavoided.Buthowhighishigh?

Proteinintakeandcardiovasculardiseaserelationshipisanother
variablethatisunclear
Therealsomaybeethnicdifferencesinresponsetoproteinintake.

Conclusion
Atthistime,
itappearsthatnospecialrecommendations
forproteininakeinpatientswithdiabetic
kidneydiseaseshouldbemadeotherthan
avoidinghighproteinintake
(whateverthatis).