Dietary Changes to Slow Chronic
Kidney Disease Progression
Kalani Raphael, MD MS
Division of Nephrology & Hypertension
University of Utah
Salt 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
Hypertension
Diabetes
Cystic kidney disease
Glomerulonephritis
Interstitial nephritis
Reflux
Obstruction
Stages of CKD
Stage 1
Stage 2
Stage 3
Stage 4
Stage 5
eGFR
≥ 90
60 - 89
30 - 59
15 - 29
< 15
# of Americans Mortality Risk
7.7 million
~2x
7.3 million
~2x
10 million
25% over 5 years
400,000
50% over 5 years
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
+
H ot
Dogs
H+
Urine
H+
NH4+
H+
H+
H+
NH4+
NH4+
NH4++
NH4
Excreted
NH3
NH3
H+
Urine
H+
NH4+
H+
NH3
NH3
NH3
H+
H+
NH4+
NH4+
NH4++
NH4
Excreted
NH3
NH3
NH3
NH3
NH3
Kidney Tubular Cell
H+ot Dog
↑ [NH3]
Complement
Activation
Endothelin-1
Kidney injury
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
Dialysis free survival
Sodium bicarbonate may slow
progression in moderate CKD
Sodium bicarbonate
Control
Stage 4/5 CKD
Serum bicarbonate 16 – 20
Time (months)
De Brito-Ashurst et al J Am Soc Neph 2009.
Sodium bicarbonate may slow
progression in early CKD
Stage 2 hypertensive CKD patients
Albuminuria
Normal serum bicarbonate
Mahajan et al Kidney International 2010
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 intake
2. 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 A
*Modification of Diet in Renal Disease
Change in GFR
GFR 25-55 ml/min
Low Protein (0.58 gm/kg/day)
Usual Protein (1.3 gm/kg/day)
Klahr et al. NEJM 1994
ESRD
p=NS for both
ESRD or Death
Levey et al AJKD 2006.
MDRD Study – Study B
GFR 13-24 ml/min
Low Protein (0.58 gm/kg/day
Very Low Protein (0.28 gm/kg/day
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.
65
60
55
50
45
40
35
30
Serum Bicarbonate (mM)
Renal Acid Load (mmol/d)
22
21.5
21
20.5
20
19.5
19
18.5
Bicarbonate
Fruit/Veg
Baseline
One year
Baseline
One year
8-hr Urinary H+ Excretion (mM)
30
Due to ↓NH4+
20
10
0
Baseline
One year
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 & vegetables
1. Reduces acid burden
2. Reduces renal ammonia production
3. Normalizes serum bicarbonate
4. 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
CKD
Fructose
Fructose
Uric Acid
Inflammation
Oxidative stress
Reduced NO
Other
Mechanisms??
Kidney Injury
CKD
Progression
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
CKD rats
Normal rats
Nakayama et al. AJP Renal Phys 2010. Gersch et al AJP Renal Phys 2007.
BUN mg/dL
80
70
60
50
Normal Diet
40
Fructose Diet
30
Dextrose Diet
20
10
0
Baseline
Week 5
Gersch et al AJP Renal Phys 2007.
Week 9
Age-Adjusted Prevalence of Albuminuria
20.0%
18.0%
14.0%
12.2%
12.0%
10.0%
15.3%
p<0.001
16.0%
8.7%
9.6%
8.0%
6.0%
4.0%
2.0%
0.0%
0
1
2
3
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
80
Fructose Intake
60
40
20
0
Basal
Low Fructose
Basal
7.2
7
6.8
6.6
6.4
6.2
6
Uric Acid
Basal
SBP
Low Fructose
Basal
TGF-beta
132
50
130
40
128
30
20
126
10
124
0
Basal
Low Fructose
Basal
Basal
Low Fructose
Brymora et al Nephrol Dial Trans 2012.
Basal
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
Red meat, processed
Refined grains
High-fat dairy
Saturated, trans-fats
High cholesterol
Sugary desserts/drinks
DASH Diet
Poultry, fish
Whole grains
Low-fat dairy
Unsaturated fats
Fresh fruit
Vegetables
‘Westerner’ Diet & CKD progression
1.5
Q2
Q3
Q4
Reference
Odds Ratio
2
Q1
1
Western Diet
0.5
0
Lin et al AJKD 2011.
‘DASHier’ Diet & CKD progression
1.5
Q2
Q3
Q4
Reference
Odds Ratio
2
Q1
Western Diet
DASH Diet
1
0.5
0
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.
2.
3.
4.
5.
6.
7.
8.
Stop soda, fruit drinks
Rare desserts
Fresh fruit and vegetables (monitor K+)
Fish, chicken breast
Plant based protein, nuts
Less red meat, processed/canned foods
Low fat milk (monitor phosphorus)
Low salt