Advertisement
American Journal of Kidney Diseases

Association of Dialysate Bicarbonate Concentration With Mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

      Background

      Most hemodialysis patients worldwide are treated with bicarbonate dialysis using sodium bicarbonate as the base. Few studies have assessed outcomes of patients treated with different dialysate bicarbonate levels, and the optimal concentration remains uncertain.

      Study Design

      The Dialysis Outcomes and Practice Patterns Study (DOPPS) is an international prospective cohort study.

      Setting & Participants

      This study included 17,031 patients receiving thrice-weekly in-center hemodialysis from 11 DOPPS countries (2002-2011).

      Predictor

      Dialysate bicarbonate concentration.

      Outcomes

      All-cause and cause-specific mortality and first hospitalization, using Cox regression to estimate the effects of dialysate bicarbonate concentration, adjusting for potential confounders.

      Measurements

      Demographics, comorbid conditions, laboratory values, and prescriptions were abstracted from medical records.

      Results

      Mean dialysate bicarbonate concentration was 35.5 ± 2.7 (SD) mEq/L, ranging from 32.2 ± 2.3 mEq/L in Germany to 37.0 ± 2.6 mEq/L in the United States. Prescription of high dialysate bicarbonate concentration (≥38 mEq/L) was most common in the United States (45% of patients). Approximately 50% of DOPPS facilities used a single dialysate bicarbonate concentration. 3,913 patients (23%) died during follow-up. Dialysate bicarbonate concentration was associated positively with mortality (adjusted HR, 1.08 per 4 mEq/L higher [95% CI, 1.01-1.15]; HR for dialysate bicarbonate ≥38 vs 33-37 mEq/L, 1.07 [95% CI, 0.97-1.19]). Results were consistent across levels of pre–dialysis session serum bicarbonate and between facilities that used a single dialysate bicarbonate concentration and those that prescribed different concentrations to individual patients. The association of dialysis bicarbonate concentration with mortality was stronger in patients with longer dialysis vintage.

      Limitations

      Due to the observational nature of the present study, we cannot rule out that the reported associations may be biased by unmeasured confounders.

      Conclusions

      High dialysate bicarbonate concentrations, especially prolonged exposure, may contribute to adverse outcomes, likely through the development of postdialysis metabolic alkalosis. Additional studies are warranted to identify the optimal dialysate bicarbonate concentration.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Franch H.A.
        • Mith W.E.
        Catabolism in uremia: the impact of metabolic acidosis.
        J Am Soc Nephrol. 1998; 9: S78-S81
        • Uribarri J.
        • Levin N.W.
        • Delmez J.
        • et al.
        Association of acidosis and nutritional parameters in hemodialysis patients.
        Am J Kidney Dis. 1999; 34: 493-499
        • National Kidney Foundation
        K/DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure.
        Am J Kidney Dis. 2000; 35: S17-S104
        • Eknoyan G.
        • Levin A.
        • Levin N.W.
        Bone metabolism and disease in chronic kidney disease/KDOQI guidelines.
        Am J Kidney Dis. 2003; 42: S1-S201
        • Locatelli F.
        • Covic A.
        • Chazot C.
        • Leunissen K.
        • Luño J.
        • Yaqoob M.
        Optimal composition of the dialysate, with emphasis on its influence on blood pressure.
        Nephrol Dial Transplant. 2004; 19: 785-796
        • Oettinger C.W.
        • Oliver J.C.
        Normalization of uremic acidosis in hemodialysis patients with a high bicarbonate dialysate.
        J Am Soc Nephrol. 1993; 3: 1804-1807
        • Graham K.A.
        • Reaich D.
        • Channon S.M.
        • Downie S.
        • Goodship T.H.
        Correction of acidosis in hemodialysis decreases whole-body protein degradation.
        J Am Soc Nephrol. 1997; 8: 632-637
        • Williams A.J.
        • Dittmer I.D.
        • McArley A.
        • Clarke J.
        High bicarbonate dialysate in haemodialysis patients: effects on acidosis and nutritional status.
        Nephrol Dial Transplant. 1997; 12: 2633-2637
        • Kooman J.P.
        • Deutz N.E.
        • Zijlmans P.
        • et al.
        The influence of bicarbonate supplementation on plasma levels of branched-chain amino acids in haemodialysis patients with metabolic acidosis.
        Nephrol Dial Transplant. 1997; 12: 2397-2401
        • Graziani G.
        • Casati S.
        • Passerini P.
        • Crepaldi M.
        • Campise M.
        • Ambroso G.
        Pathophysiology and clinical consequences of metabolic alkalosis in hemodialyzed patients.
        Arch Ital Urol Nefrol Androl. 1987; 59: 105-111
        • Gabutti L.
        • Ferrari N.
        • Giudici G.
        • Mombelli G.
        • Marone C.
        Unexpected haemodynamic instability associated with standard bicarbonate haemodialysis.
        Nephrol Dial Transplant. 2003; 18: 2369-2376
        • Di Iorio B.
        • Torraca S.
        • Piscopo C.
        • et al.
        Dialysate bath and QTc interval in patients on chronic maintenance hemodialysis: pilot study of single dialysis effects.
        J Nephrol. 2012; 25: 653-660
        • Roderick P.J.
        • Willis N.S.
        • Blakeley S.
        • Jones C.
        • Tomson C.
        Correction of chronic metabolic acidosis for chronic kidney disease patients.
        Cochrane Database Syst Rev. 2007; 1 (CD001890)
        • Young E.W.
        • Goodkin D.A.
        • Mapes D.L.
        • et al.
        The Dialysis Outcomes and Practice Patterns Study (DOPPS): an international hemodialysis study.
        Kidney Int Suppl. 2000; 74: S74-S81
        • Pisoni R.L.
        • Gillespie B.W.
        • Dickinson D.M.
        • Chen K.
        • Kutner M.
        • Wolfe R.A.
        The Dialysis Outcomes and Practice Patterns Study: design, data elements, and methodology.
        Am J Kidney Dis. 2004; 44: S7-S15
        • Saran R.
        • Bragg-Gresham J.L.
        • Wizemann V.
        • et al.
        Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS.
        Kidney Int. 2006; 69: 1222-1228
      1. SAS/STAT User's Guide Version 8.
        SAS Institute, Cary, NC2000
        • Van Buuren S.
        • Boshuizen H.C.
        • Knook D.L.
        Multiple imputation of missing blood pressure covariates in survival analysis.
        Stat Med. 1999; 18: 681-694
      2. Raghunathan TE, Solenberger PW, Van Hoewyk J. IVEware: Imputation and Variance Estimation Software. Ann Arbor, MI: Survey Methodology Program, Survey Research Center, Institute for Social Research, University of Michigan.

        • Little R.J.A.
        • Rubin D.B.
        Statistical Analysis With Missing Data. Wiley, New York, NY1987
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • Pocock S.J.
        • Gøtzsche P.C.
        • Vandenbroucke J.P.
        STROBE initiative: the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        Lancet. 2007; 370: 1453-1457
        • Brady J.P.
        • Hasbargen J.A.
        Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients.
        Am J Kidney Dis. 1998; 31: 35-40
        • Sonikian M.
        • Gogusev J.
        • Zingraff J.
        • et al.
        Potential effect of metabolic acidosis on beta 2-microglobulin generation: in vivo and in vitro studies.
        J Am Soc Nephrol. 1996; 7: 350-356
        • Ahmad S.
        • Pagel M.
        • Vizzo J.
        • Scribner B.H.
        Effect of the normalization of acid-base balance on postdialysis plasma bicarbonate.
        Trans Am Soc Artif Intern Organs. 1980; 26: 318-322
        • Harris D.C.
        • Yuill E.
        • Chesher D.W.
        Correcting acidosis in hemodialysis: effect on phosphate clearance and calcification risk.
        J Am Soc Nephrol. 1995; 6: 1607-1612
        • Mitch W.E.
        • Clark A.S.
        Specificity of the effects of leucine and its metabolites on protein degradation in skeletal muscle.
        Biochem J. 1984; 222: 579-586
        • Avram M.M.
        • Goldwasser P.
        • Erroa M.
        • Fein P.A.
        Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of prealbumin and other nutritional and metabolic markers.
        Am J Kidney Dis. 1994; 23: 91-98
        • Graham K.A.
        • Hoenich N.A.
        • Goodship T.H.
        Pre and interdialytic acid-base balance in hemodialysis patients.
        Int J Artif Organs. 2001; 24: 192-196
        • Alfakir M.
        • Moammar M.Q.
        • Ali M.I.
        • et al.
        Pulmonary gas exchange during hemodialysis: a comparison of subjects with and without COPD on bicarbonate hemodialysis.
        Ann Clin Lab Sci. 2011; 41: 315-320
        • Pande S.
        • Raja R.
        • Bloom E.
        • Chewaproug D.
        • Dissanayake I.
        Effect of dialysate baths on serum bicarbonate levels in hemodialysis patients [abstract 234].
        Am J Kidney Dis. 2011; 57: A75
        • Heguilen R.M.
        • Sciurano C.
        • Bellusci A.D.
        • et al.
        The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.
        Nephrol Dial Transplant. 2005; 20: 591-597
        • Sethi D.
        • Curtis J.R.
        • Topham D.L.
        • Gower P.E.
        Acute metabolic alkalosis during haemodialysis.
        Nephron. 1989; 51: 119-120
        • Kaye M.
        • Somerville P.J.
        • Lowe G.
        • Ketis M.
        • Schneider W.
        Hypocalcemic tetany and metabolic alkalosis in a dialysis patient: an unusual event.
        Am J Kidney Dis. 1997; 30: 440-444
        • Sam R.
        • Vaseemuddin M.
        • Leong W.H.
        • Rogers B.E.
        • Kjellstrand C.M.
        • Ing T.S.
        Composition and clinical use of hemodialysates.
        Hemo Int. 2006; 10: 15-28
        • Gabutti L.
        • Ross V.
        • Duchini F.
        • Mombelli G.
        • Marone C.
        Does bicarbonate transfer have relevant hemodynamic consequences in standard hemodialysis?.
        Blood Purif. 2005; 23: 365-372
        • Ibels L.S.
        The pathogenesis of metastatic calcification in uraemia.
        Prog Biochem Pharmacol. 1980; 17: 242-250
        • Uribarri J.
        Moderate metabolic acidosis and its effects on nutritional parameters in hemodialysis patients.
        Clin Nephrol. 1997; 48: 238-240
        • Vermeulen M.
        • Giordano M.
        • Trevani A.S.
        • et al.
        Acidosis improves uptake of antigens and MHC class I-restricted presentation by dendritic cells.
        J Immunol. 2004; 172: 3196-3204
        • Uribarri J.
        How should dialysis fluid be individualized for the chronic hemodialysis patient?.
        Semin Dial. 2008; 21: 221-223
        • Bommer J.
        • Locatelli F.
        • Satayathum S.
        • et al.
        Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS).
        Am J Kidney Dis. 2004; 44: 661-671
        • Lowrie E.G.
        • Lew N.L.
        Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.
        Am J Kidney Dis. 1990; 15: 458-482
        • Wu D.Y.
        • Shinaberger C.S.
        • Regidor D.L.
        • McAllister C.J.
        • Kopple J.D.
        • Kalantar-Zadeh K.
        Association between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alkalotic?.
        Clin J Am Soc Nephrol. 2006; 1: 70-78
      3. FDA Safety Communication: Dialysate Concentrates and Alkali Dosing Errors with Hemodialysis. US Food and Drug Administration.
        (Accessed August 16, 2012)