Association of dialysate bicarbonate concentration with mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Abstract

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.

Keywords: Dialysis Outcomes and Practice Patterns Study (DOPPS); Hemodialysis; observational; outcomes; statistics.

Figure 1. Distribution of dialysate bicarbonate prescription, by country

ANZ=Australia and New Zealand; BE= Belgium; CA= Canada; FR= France; GE= Germany; IT: Italy; SP= Spain; SW= Sweden; UK= United Kingdom; US= United States.

Figure 2. Association between prescribed dialysate bicarbonate (per 4 mEq/L higher) and all-cause mortality, by levels of adjustment

*Unadjusted Cox model stratified by DOPPS phase and country and accounted for facility clustering; **Patient-level adjustments: vintage, residual kidney function, catheter use, single pool Kt/V, prescribed blood flow rate, treatment time, serum albumin, ferritin, creatinine, calcium, phosphorus, white blood cell count, hemoglobin, dialysate Ca, and dialysate K; ***Facility-level adjustments: % catheter use and % Kt/V < 1.2; DB=Dialysate Bicarbonate, BMI=Body Mass Index.

Figure 3. Association between prescribed dialysate bicarbonate (per 4 mEq/L higher) and various clinical outcomes

Cox models adjusted for age, sex, body mass index, 13 summary comorbid conditions, vintage, residual kidney function, catheter use, single pool Kt/V, prescribed blood flow rate, treatment time, serum albumin, ferritin, creatinine, calcium, phosphorus, white blood cell count, hemoglobin, dialysate Ca, dialysate K, facility % catheter use, and facility % Kt/V <1.2, stratified by DOPPS phase and country, and accounted for facility clustering effects. DB=Dialysate Bicarbonate.

Figure 4. Association between 3 categories of prescribed dialysate bicarbonate and all-cause mortality, overall and by serum bicarbonate

Two separate Cox models adjusted for age, sex, body mass index, 13 summary comorbid conditions, vintage, residual kidney function, catheter use, single pool Kt/V, prescribed blood flow rate, treatment time, serum albumin, ferritin, creatinine, calcium, phosphorus, white blood cell count, hemoglobin, dialysate Ca, dialysate K, facility % catheter use, and facility % Kt/V <1.2, stratified by DOPPS phase and country, and accounted for facility clustering effects; S.Bic=Serum Bicarbonate.

Figure 5. Association between categories of serum bicarbonate and all-cause mortality, in non-individualized and individualized facilities

Two separate Cox models adjusted for age, sex, body mass index, 13 summary comorbid conditions, vintage, residual kidney function, catheter use, single pool Kt/V, prescribed blood flow rate, treatment time, serum albumin, ferritin, creatinine, calcium, phosphorus, white blood cell count, hemoglobin, dialysate bicarbonate, facility % catheter use, and facility % Kt/V <1.2, stratified by DOPPS phase and country, and accounted for facility clustering effects. Distribution of serum bicarbonate categories is shown overall; distributions differ minimally between individualized and non-individualized facilities.