Serum bicarbonate and long-term outcomes in CKD.

BACKGROUND A low serum bicarbonate level is prevalent in chronic kidney disease (CKD); however, its relationship to long-term outcomes is unclear. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 942 screened but non-randomized individuals and 839 randomized participants with baseline serum bicarbonate measurements with stage 2-4 CKD. FACTOR Serum bicarbonate level categorized into quartiles. OUTCOMES Kidney failure, all-cause mortality, and a composite outcome of mortality and kidney failure. MEASUREMENTS Local laboratories at each participating site measured bicarbonate in fasting serum samples. Kidney failure outcomes were obtained from the US Renal Data System, and mortality data, from the National Death Index. RESULTS Mean glomerular filtration rate (GFR) was 39 ± 21 (SD) mL/min/1.73 m(2) and serum bicarbonate level was 23.3 ± 3.8 mEq/L. Kidney failure rates were 72%, 64%, 50%, and 41%; mortality rates were 31%, 25%, 21%, and 25%, and rates of the composite outcome were 78%, 71%, 58%, and 54% in bicarbonate quartiles 1, 2, 3, and 4, respectively. In analyses adjusted for demographic and cardiovascular disease factors, serum albumin level, proteinuria, and cause of kidney disease, compared with quartile 4, quartile 1 was associated with a 2.22 HR (95% CI, 1.83-2.68) of kidney failure; 1.39 HR (95% CI, 1.07-1.18) of all-cause mortality; and 1.36 HR (95% CI, 1.15-1.62) of the composite outcome. These associations were rendered nonsignificant with adjustment for GFR (kidney failure HR, 1.05 [95% CI, 0.87-1.28]; all-cause mortality HR, 0.99 [95% CI, 0.75-1.13]; composite HR, 1.04 [95% CI, 0.87-1.24]). LIMITATIONS Single baseline measurement of serum bicarbonate. CONCLUSIONS Low serum bicarbonate level was associated with increased risk of long-term outcomes in nondiabetic patients with CKD. However, this risk is not independent of baseline GFR. Clinical trials are necessary to evaluate whether bicarbonate supplementation slows the progression of CKD.

[1]  J. Boggia,et al.  Calcium citrate ameliorates the progression of chronic renal injury. , 2004, Kidney international.

[2]  P. Roderick,et al.  Correction of chronic metabolic acidosis for chronic kidney disease patients. , 2007, The Cochrane database of systematic reviews.

[3]  G. Beck,et al.  The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease , 1994 .

[4]  B. Astor,et al.  Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. , 2004, Kidney international.

[5]  F. Scolari,et al.  Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[6]  G. Beck,et al.  Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  G. Beck,et al.  Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. , 1997, Kidney international.

[8]  W. D. Lotspeich.  RENAL HYPERTROPHY IN METABOLIC ACIDOSIS AND ITS RELATION TO AMMONIA EXCRETION. , 1965, The American journal of physiology.

[9]  K. Chow,et al.  Oral sodium bicarbonate for the treatment of metabolic acidosis in peritoneal dialysis patients: a randomized placebo-control trial. , 2003, Journal of the American Society of Nephrology : JASN.

[10]  T. Hostetter,et al.  Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3. , 1985, The Journal of clinical investigation.

[11]  Neil R. Powe,et al.  Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. , 2007, Kidney international.

[12]  F. Locatelli,et al.  Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS). , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  K. Kalantar-Zadeh,et al.  Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  T. Hostetter,et al.  Serum bicarbonate levels and the progression of kidney disease: a cohort study. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[15]  M. Raftery,et al.  Bicarbonate supplementation slows progression of CKD and improves nutritional status. , 2009, Journal of the American Society of Nephrology : JASN.

[16]  E G Lowrie,et al.  Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. , 1990, American journal of kidney diseases : the official journal of the National Kidney Foundation.