Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study

Abstract

Background: Prior studies have developed a chronic kidney disease-mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients.

Methods: We studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3-5 (2005-15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5-5.5 mg/dL; Ca, 8.4-10.2 mg/dL; PTH, 150-600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2-3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS).

Results: MBD 2/3 above target was observed in 10-14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10-1.82]} and composite events [HR 1.23 (95% CI 1.10-1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28-2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80-1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions.

Conclusions: Simultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

Keywords: CKD-MBD; DOPPS; calcium; hemodialysis; parathyroid hormone; phosphorus.

FIGURE 1

HRs for MBD 2/3 above target versus MBD 0, by region. CAN, Canada; DRS, disease risk score; EUR, Europe. Europe includes Belgium, France, Germany, Italy, Spain, Sweden and the UK. Composite outcome defined as death or hospitalization. DRS adjustment variables include age, Liu’s comorbidity index, years with ESRD (vintage), serum albumin, hemoglobin, BMI, single-pool K_t/V, number of patients dialyzing in the study facility, male sex, black race (USA only), data source (electronic health record versus other; USA only), primary cause of ESRD, smoking history (ever versus never smoked), hypertension, history of fracture, hospitalization within 120 days prior to the index date, DOPPS study phase and country (Europe only).

FIGURE 2

HRs for MBD 2/3 outside target versus MBD 0, by region. CAN, Canada; DRS, disease risk score; EUR, Europe. Europe includes Belgium, France, Germany, Italy, Spain, Sweden and the UK. Composite outcome defined as death or hospitalization. DRS adjustment variables include age, Liu’s comorbidity index, years with ESRD (vintage), serum albumin, hemoglobin, body mass index, single-pool K_t/V, number of patients dialyzing in the study facility, male sex, black race (USA only), data source (electronic health record versus other; USA only), primary cause of ESRD, smoking history (ever versus never smoked), hypertension, history of fracture, hospitalization within 120 days prior to the index date, DOPPS study phase and country (Europe only) .