Dietary Changes to Slow Chronic Kidney Disease Progression

Kalani Raphael, MD MSDivision of Nephrology & Hypertension

University of UtahSalt Lake City VA Health Care System

I have no financial relationships to disclose

Objectives

• Overview of chronic kidney disease (CKD)

• Promising dietary intervention targets– Dietary acid – Fructose

• Dietary recommendations for CKD patients

CKD

Diagnosis– Glomerular filtration rate (GFR) < 60 ml/min

OR– Evidence of kidney injury when GFR ≥ 60 ml/min• Examples of kidney injury:– Albuminuria ≥ 30 mg/gm– Polycystic kidney disease– Glomerular hematuria (IgA nephropathy)

Causes of CKD

HypertensionDiabetesCystic kidney diseaseGlomerulonephritisInterstitial nephritisReflux Obstruction

Stages of CKD

eGFR # of Americans Mortality RiskStage 1 ≥ 90 7.7 million ~2xStage 2 60 - 89 7.3 million ~2xStage 3 30 - 59 10 million 25% over 5 yearsStage 4 15 - 29 400,000 50% over 5 yearsStage 5 < 15 600,000 20% per year

Levey et al. Kidney Int, 2011.

CKD - A Significant Burden

• 25 million Americans have CKD– 12% of US population

• Advancing CKD poor outcomes☞• ESRD accounts for 6% of Medicare budget• Kidney transplantation – scarce resource

Strategies to slow CKD progression

• ACE-I or ARB• Blood pressure control

< 140/90< 130/80

• Glucose control

Diet?Exercise?Vitamins?

REDUCE DIETARY ACID INTAKE

Acid

• A major function of kidney is to regulate H+ • Avg renal acid burden = 1 meq H+ per kg/day• Sources of acid–Diet• Protein: Red meat > fish > plant

– Endogenous production• Ketoacids, lactic acid

NH4+

Excreted

Urine

NH4+

NH4+

NH4+

NH4+

NH3

NH3

NH3

NH3 NH3

H+

H+

H+

H+

H+

H+otDogs

NH4+

Excreted

Urine

NH4+

NH4+

NH4+

NH4+

NH3

NH3

NH3

NH3 NH3

H+

H+

H+

H+

H+

↑ [NH3]

ComplementActivation

Kidney injury

Kidney Tubular Cell

Endothelin-1

H+ot Dog

CKD Progression

Does reducing renal acid burden slow CKD progression?

Sodium Bicarbonate

• Alkaline agent• Neutralizes non-volatile acid• Typically prescribed when serum bicarbonate

< 22 mmol/L in CKD patients– Bone protection– Reduce protein catabolism

Sodium bicarbonate may slow progression in moderate CKD

Dial

ysis

free

surv

ival

Time (months)

Sodium bicarbonate

Control

De Brito-Ashurst et al J Am Soc Neph 2009.

Stage 4/5 CKDSerum bicarbonate 16 – 20

Sodium bicarbonate may slow progression in early CKD

Mahajan et al Kidney International 2010

Stage 2 hypertensive CKD patientsAlbuminuriaNormal serum bicarbonate

Summary of Sodium Bicarbonate

• Sodium bicarbonate reduces acid load to the kidney

• Reduces renal ammonia production• Reduces complement-mediated kidney injury

• Can we reduce dietary acid load?1. Reduce protein intake2. Increase fruits and vegetables

Low protein diet in CKD

Improves:• Phosphorus• BP• H+

• Proteinuria• Insulin sensitivity

Disadvantages:• Protein-energy

malnutrition• Decreased muscle• Complex• Inconvenient

MDRD* Study – Study ACh

ange

in G

FR

Low Protein (0.58 gm/kg/day)

Usual Protein (1.3 gm/kg/day)

Klahr et al. NEJM 1994

*Modification of Diet in Renal Disease

GFR 25-55 ml/min

ESRD

ESRD or Death

p=NS for both

Levey et al AJKD 2006.

MDRD Study – Study B

Low Protein (0.58 gm/kg/day

Very Low Protein (0.28 gm/kg/day

GFR 13-24 ml/min

Klahr et al. NEJM 1994

ESRD

Death

Menon et al AJKD 2009.

Low protein diet - Summary

• Theoretically beneficial

• Clinical trials inconclusive– Unlikely to be replicated

• Personal recommendation– Substitute red meat with poultry, fish, plant

protein

Fruits & Vegetables – Interventional Study

Key entry criteria• Stage 4 CKD (GFR 15 – 29)• Metabolic acidosis (Bicarb < 22)Intervention• Sodium bicarbonate (1meq/kg/day) or• Fruits and vegetables (reduce acid load by ½)

Goraya et al Kidney Int 2013.

F/V Strategy

• Apples• Apricots• Oranges• Peaches• Pears• Raisins• Strawberries

• Carrots• Cauliflower• Eggplant• Lettuce

• Potatoes• Spinach• Tomatoes• Zucchini

Enough given for all household members

Provided free from local food bank

Goraya et al Kidney Int 2013.

Baseline One year3035404550556065

Renal Acid Load (mmol/d)

BicarbonateFruit/Veg

Baseline One year18.5

1919.5

2020.5

2121.5

22

Serum Bicarbonate (mM)

Baseline One year05

1015202530

8-hr Urinary H+ Excretion (mM)

Due to ↓NH4+

Goraya et al Kidney Int 2013.

Other findings

Bicarbonate and fruits/vegetables reduce urinary:1. Albumin

No hyperkalemia observed in F/V group• Pts had K < 4.7 at baseline

Goraya et al Kidney Int 2013.

Augmenting diet with fruits & vegetables1. Reduces acid burden2. Reduces renal ammonia production3. Normalizes serum bicarbonate4. Ameliorates kidney injury

Practical Recommendation F/V

• Increase fruits/veg in the diet

• Caution if K is > 5.0– Reduce K with diuretics

REDUCE FRUCTOSE INTAKE

Fructose

Uric Acid HTN

Fructose

CKD

Fructose

Uric Acid

InflammationOxidative stressReduced NO

Kidney Injury

CKD Progression

OtherMechanisms??

Fructose

• Primary sources in Western diet– High fructose corn syrup– Table sugar (sucrose)

• Avg American consumes 64 pounds of fructose/yr

• In large quantities, systemic levels high enough to be filtered by kidney

Nakayama et al. AJP Renal Phys 2010. Gersch et al AJP Renal Phys 2007.

Normal rats

CKD rats

Baseline Week 5 Week 90

1020304050607080

BUN mg/dL

Normal DietFructose DietDextrose Diet

Gersch et al AJP Renal Phys 2007.

0 1 2 30.0%2.0%4.0%6.0%8.0%

10.0%12.0%14.0%16.0%18.0%20.0%

8.7%9.6%

12.2%

15.3%

Age-Adjusted Prevalence of Albuminuria

p<0.001

Number of sugary soft drinks per day

Shohan et al PLOS One 2008.

Shohan et al PLOS One 2008.

Low fructose diet – interventional study

• 28 non-DM CKD stage 2 or 3• Basal fructose intake (~60 gm/day)• 6 wk low fructose (~12 gm/day)– Designed to reduce by 80%

• Return to basal diet for 6 wks (~53 gm/day)• No diff in caloric intake• Reduce consumption of sucrose-sweetened

and artificially sweetened drinks & foods

Basal Low Fructose Basal0

10203040506070

Fructose Intake

Basal Low Fructose Basal6

6.26.46.66.8

77.2

Uric Acid

Basal Low Fructose Basal125126127128129130131132

SBP

Brymora et al Nephrol Dial Trans 2012.

Basal Low Fructose Basal0

10

20

30

40

50

TGF-beta

Summary - Fructose

Low fructose diet…• Improves uric acid, BP• May reduce renal inflammation• No long-term interventional studies

• It’s not good for you.

DIETARY RECOMMENDATIONS FOR CKD PATIENTS

Western Diet DASH DietRed meat, processed Poultry, fishRefined grains Whole grainsHigh-fat dairy Low-fat dairySaturated, trans-fats Unsaturated fatsHigh cholesterol Fresh fruitSugary desserts/drinks Vegetables

‘Westerner’ Diet & CKD progression

0

0.5

1

1.5

2

Western Diet

Q1 Q2 Q3 Q4

Refe

renc

e

Odd

s Rati

o

Lin et al AJKD 2011.

‘DASHier’ Diet & CKD progression

0

0.5

1

1.5

2

Western DietDASH Diet

Q1 Q2 Q3 Q4

Refe

renc

e

Odd

s Rati

o

Lin et al AJKD 2011.

Conclusion

• High H+ & fructose cause kidney injury in CKD

• Average American diet high in both

• It is sensible to increase fruits & vegetables, reduce animal protein, and eliminate sugary foods/drinks.

Summary - Dietary Recommendations for CKD

1. Stop soda, fruit drinks2. Rare desserts3. Fresh fruit and vegetables (monitor K+)4. Fish, chicken breast5. Plant based protein, nuts6. Less red meat, processed/canned foods7. Low fat milk (monitor phosphorus)8. Low salt