1. 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

2. I have no financial relationships to disclose

3. Objectives Overview of chronic kidney disease (CKD)
Promising dietary intervention targets
Dietary acid
Fructose
Dietary recommendations for CKD patients

4. 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)

5. Causes of CKD
Hypertension Diabetes Cystic kidney disease Glomerulonephritis Interstitial nephritis Reflux Obstruction
APOL1 gene mutations in AA pts, their nephrosclerosis may not be d/t HTN

6. Stages of CKD eGFR # of Americans Mortality Risk Stage 1 ≥ 90
7.7 million
~2x
Stage 2
7.3 million
Stage 3
10 million
25% over 5 years
Stage 4
400,000
50% over 5 years
Stage 5
< 15
600,000
20% per year
Levey et al. Kidney Int, 2011.

7. 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

8. Strategies to slow CKD progression
ACE-I or ARB
Blood pressure control
< 140/90
< 130/80
Glucose control

9. Diet?
Exercise?
Vitamins?

10. Reduce Dietary Acid intake

11. 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

12. H+ot
Dogs
NH4+
Excreted
Urine
NH3 H+
NH4+
Excreted
Urine
NH3 H+

13. ↑ [NH3] Kidney Tubular Cell H+ot Dog Kidney injury CKD Progression
Complement
Activation
Endothelin-1
Kidney injury
CKD Progression

14. Does reducing renal acid burden slow CKD progression?

15. Sodium Bicarbonate Alkaline agent Neutralizes non-volatile acid
Typically prescribed when serum bicarbonate < 22 mmol/L in CKD patients
Bone protection
Reduce protein catabolism
Consider talking about causes of acidosis in CKD

16. Sodium bicarbonate may slow progression in moderate CKD
Control
Dialysis free survival
Stage 4/5 CKD
Serum bicarbonate 16 – 20
Time (months)
De Brito-Ashurst et al J Am Soc Neph 2009.

17. Sodium bicarbonate may slow progression in early CKD
Stage 2 hypertensive CKD patients
Albuminuria
Normal serum bicarbonate
Mahajan et al Kidney International 2010

18. 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?
Reduce protein intake
Increase fruits and vegetables

19. Low protein diet in CKD Improves: Phosphorus BP H+ Proteinuria
Insulin sensitivity
Disadvantages:
Protein-energy malnutrition
Decreased muscle
Complex
Inconvenient

20. MDRD* Study – Study A Low Protein (0.58 gm/kg/day)
*Modification of Diet in Renal Disease
GFR ml/min
Low Protein (0.58 gm/kg/day)
Change in GFR
Achieved: 1.11 vs 0.73
Usual Protein (1.3 gm/kg/day)
Klahr et al. NEJM 1994

21. ESRD
p=NS for both
ESRD or Death
Levey et al AJKD 2006.

22. MDRD Study – Study B GFR 13-24 ml/min Low Protein (0.58 gm/kg/day
Supplemented with ketoacid-amino acid combination
Achieved 0.69 v 0.46
Very Low Protein (0.28 gm/kg/day
Klahr et al. NEJM 1994

23. ESRD
Death
Menon et al AJKD 2009.

24. Low protein diet - Summary
Theoretically beneficial
Clinical trials inconclusive
Unlikely to be replicated
Personal recommendation
Substitute red meat with poultry, fish, plant protein

25. 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.

26. 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.

27. Due to ↓NH4+
Goraya et al Kidney Int 2013.

28. Other findings Bicarbonate and fruits/vegetables reduce urinary:
Albumin
No hyperkalemia observed in F/V group
Pts had K < 4.7 at baseline
Goraya et al Kidney Int 2013.

29. Augmenting diet with fruits & vegetables
Reduces acid burden
Reduces renal ammonia production
Normalizes serum bicarbonate
Ameliorates kidney injury

30. Practical Recommendation F/V
Increase fruits/veg in the diet
Caution if K is > 5.0
Reduce K with diuretics

31. Reduce fructose intake

32. Fructose
Uric Acid
HTN
CKD
Fructose

33. Other Mechanisms?? Fructose Uric Acid Inflammation Oxidative stress
Reduced NO
Kidney Injury
CKD
Progression

34. 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

35. Nakayama et al. AJP Renal Phys 2010. Gersch et al AJP Renal Phys 2007.
CKD rats
Normal rats
No change in uric acid
Nakayama et al. AJP Renal Phys Gersch et al AJP Renal Phys 2007.

36. Gersch et al AJP Renal Phys 2007.

37. Number of sugary soft drinks per day
Non-DM adults NHANES
Number of sugary soft drinks per day
Shohan et al PLOS One 2008.

38. Shohan et al PLOS One 2008.

39. 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

40. Brymora et al Nephrol Dial Trans 2012.

41. Summary - Fructose Low fructose diet… Improves uric acid, BP
May reduce renal inflammation
No long-term interventional studies
It’s not good for you.

42. Dietary recommendations for ckd patients

43. Western Diet
DASH Diet
Red meat, processed
Poultry, fish
Refined grains
Whole grains
High-fat dairy
Low-fat dairy
Saturated, trans-fats
Unsaturated fats
High cholesterol
Fresh fruit
Sugary desserts/drinks
Vegetables

44. ‘Westerner’ Diet & CKD progressionQ1 Q2 Q3 Q4
Reference
Odds Ratio
Nurses Health Study, 30% reduction of GFR
Lin et al AJKD 2011.

45. ‘DASHier’ Diet & CKD progressionQ1 Q2 Q3 Q4
Reference
Odds Ratio
Nurses Health Study
Lin et al AJKD 2011.

46. 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.

47. Summary - Dietary Recommendations for CKD
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
Sneak in 1-2 phosphorus slides