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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)
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Dietary Changes to Slow Chronic Kidney Disease Progression Kalani Raphael, MD MSDivision of Nephrology & Hypertension University of Utah Salt Lake City VA Health Care System
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 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?
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 Urine Urine H+ H+ NH3 NH3 H+ H+ NH4+ NH4+ NH3 NH3 H+ H+ NH4+ NH4+ NH3 NH3 NH4+ NH4+ H+ H+ NH3 NH3 NH4+ NH4+ NH3 NH3 NH4+ NH4+ H+ H+ Excreted Excreted
Kidney Tubular Cell H+ot Dog ↑ [NH3] Complement Activation Endothelin-1 Kidney injury 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 Sodium bicarbonate Control Dialysis free survival Stage 4/5 CKD Serum bicarbonate 16 – 20 Time (months) De Brito-Ashurst et al J Am SocNeph 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? • Reduce protein intake • 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 GFR 25-55 ml/min Low Protein (0.58 gm/kg/day) Change in GFR 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.
Due to ↓NH4+ Goraya et al Kidney Int 2013.
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.
Augmenting diet with fruits & vegetables • Reduces acid burden • Reduces renal ammonia production • Normalizes serum bicarbonate • Ameliorates kidney injury
Practical Recommendation F/V • Increase fruits/veg in the diet • Caution if K is > 5.0 • Reduce K with diuretics
Fructose Uric Acid HTN CKD Fructose
Fructose Other Mechanisms?? Uric Acid Inflammation Oxidative stress Reduced NO Kidney Injury CKD Progression
Fructose • Primary sources in Western diet • High fructose corn syrup • Table sugar (sucrose) • AvgAmerican 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.
p<0.001 Number of sugary soft drinks per day 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
Summary - Fructose Low fructose diet… • Improves uric acid, BP • May reduce renal inflammation • No long-term interventional studies • It’s not good for you.
‘Westerner’ Diet & CKD progression Q2 Q4 Q1 Q3 Reference Odds Ratio Lin et al AJKD 2011.
‘DASHier’ Diet & CKD progression Q2 Q4 Q1 Q3 Reference Odds Ratio 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 • 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