Real-world effectiveness of hemodialysis modalities: a retrospective cohort study

Abstract

Background: Results from the CONVINCE clinical trial suggest a 23% mortality risk reduction among patients receiving high-volume (> 23 L) hemodiafiltration. We assessed the real-world effectiveness of blood-based kidney replacement therapy (KRT) with hemodiafiltration vs. hemodialysis in a large, unselected patient population treated prior to and during the COVID-19 pandemic.

Methods: In this retrospective cohort study, we analyzed pseudonymized data from 85,117 adults receiving in-center care across NephroCare clinics in Europe, the Middle East, and Africa during 2019-2022. Cox regression models with KRT modality and coronavirus disease 2019 (COVID-19) status as time-varying covariates, and adjusted for multiple confounders, were used to estimate all-cause (primary) and cardiovascular (secondary) mortality. Subgroup analyses were performed for age, dialysis vintage, COVID-19 status, diabetes, and cardiovascular disease.

Results: At baseline, 55% of patients were receiving hemodialysis and 45% of patients were receiving hemodiafiltration. Baseline characteristics were similar between baseline modalities, except that hemodiafiltration patients were a median of 2 years younger, had higher percentage of fistula access (66% vs. 47%), and had longer mean dialysis vintages (4.4 years vs. 2.6 years). Compared with hemodialysis, hemodiafiltration was associated with an adjusted hazard ratio (HR) for all-cause mortality of 0.78 (95% confidence interval [Cl], 0.76-0.80), irrespective of COVID-19 infection. The pattern of a beneficial effect of hemodiafiltration was consistently observed among all analyzed subgroups. Among patients receiving high-volume hemodiafiltration (mean convection volume ≥ 23 L), the risk of death was reduced by 30% (HR, 0.70 [95% CI, 0.68-0.72]). Hemodiafiltration was also associated with a 31% reduced risk of cardiovascular death.

Conclusions: Our results suggest that hemodiafiltration has a beneficial effect on all-cause and cardiovascular mortality in a large, unselected patient population and across patient subgroups in real-world settings. Our study complements evidence from the CONVINCE trial and adds to the growing body of real-world evidence on hemodiafiltration.

Keywords: Cardiovascular mortality; Hemodiafiltration; High-flux hemodialysis; Kidney replacement therapy; Mortality.

Fig. 1

Association of HD modality and COVID-19 infection with all-cause mortality. ^aHR (95% CI) for all-cause mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at baseline (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at baseline, vascular access (frequency of 75% over the 6 months prior to baseline used to define type of vascular access, if not available at baseline), and average of systolic blood pressure over the 6 months prior to baseline, if not available at baseline. ^bHR (95% CI) for all-cause mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at baseline (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at baseline, vascular access (frequency of 75% over the 6 months prior to baseline used to define type of vascular access, if not available at baseline), average of systolic blood pressure over the 6 months prior to baseline (if not available at baseline), and parameters calculated as the average values over the 6 months prior to baseline (if not available at baseline), including IDWG, treatment frequency, duration, blood flow rate, OCM Kt/V, overhydration, albumin, sodium, calcium, iPTH, hemoglobin, platelets, and leukocytes. HR, hazard ratio; CI, confidence interval; COVID-19, coronavirus disease 2019; HD, hemodialysis; IDWG, interdialytic weight gain; OCM, online clearance monitoring; iPTH, intact parathyroid hormone

Fig. 2

Association of HD modality and COVID-19 infection with all-cause mortality in yearly-cohort analysis. ^aHR (95% CI) for all-cause mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at yearly index date (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at yearly index date, vascular access (frequency of 75% over the 6 months prior to yearly index date used to define type of vascular access, if not available at yearly index date), and average of systolic blood pressure over the 6 months prior to yearly index date, if not available at yearly index date. ^bHR (95% CI) for all-cause mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at yearly index date (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at yearly index date, vascular access (frequency of 75% over the 6 months prior to yearly index date used to define type of vascular access, if not available at yearly index date), average of systolic blood pressure over the 6 months prior to yearly index date (if not available at yearly index date), and parameters calculated as the average values over the 6 months prior to yearly index date (if not available at yearly index date), including IDWG, treatment frequency, duration, blood flow rate, OCM Kt/V, overhydration, albumin, sodium, calcium, iPTH, hemoglobin, platelets, and leukocytes. HR, hazard ratio; CI, confidence interval; COVID-19, coronavirus disease 2019; HD, hemodialysis; IDWG, interdialytic weight gain; OCM, online clearance monitoring; OCM, online clearance monitoring; iPTH, intact parathyroid hormone

Fig. 3

Association of HV-HDF and LV-HDF with all-cause mortality relative to HD. ^aModel 1: HR (95% CI) for all-cause mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at yearly index date (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at yearly index date, vascular access (frequency of 75% over the 6 months prior to yearly index date used to define type of vascular access, if not available at yearly index date), and average of systolic blood pressure over the 6 months prior to yearly index date, if not available at yearly index date. ^bModel 2: Same as Model 1, additionally adjusted for parameters calculated as the average values over the 6 months prior to yearly index date (if not available at yearly index date), including IDWG, treatment frequency, duration, blood flow rate, OCM Kt/V, overhydration, albumin, sodium, calcium, iPTH, hemoglobin, platelets, and leukocytes. ^cModel 3: Same as Model 1, additionally including country as a random effect. HR, hazard ratio; CI, confidence interval; HV-HDF, high-volume hemodiafiltration; HD, hemodialysis; LV-HDF, low-volume hemodiafiltration; COVID-19, coronavirus disease 2019; IDWG, interdialytic weight gain; OCM, online clearance monitoring; iPTH, intact parathyroid hormone

Fig. 4

Association of HD modality and COVID-19 infection with cardiovascular death. ^aHR (95% CI) for cardiovascular mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at baseline (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at baseline, vascular access (frequency of 75% over the 6 months prior to baseline used to define type of vascular access, if not available at baseline), and average of systolic blood pressure over the 6 months prior to baseline, if not available at baseline. ^bHR (95% CI) for cardiovascular mortality calculated by Cox regression models, with dialysis modality and COVID-19 status as time-dependent variables, and adjusted for age, gender, ethnicity, tobacco use, renal etiology, comorbidities at baseline (including diabetes, cardiovascular disease, infectious disease, respiratory disease, digestive disease, genitourinary disease, and malignant disease), dialysis vintage at baseline, vascular access (frequency of 75% over the 6 months prior to baseline used to define type of vascular access, if not available at baseline), average of systolic blood pressure over the 6 months prior to baseline (if not available at baseline), and parameters calculated as the average values over the 6 months prior to baseline (if not available at baseline), including IDWG, treatment frequency, duration, blood flow rate, OCM Kt/V, overhydration, albumin, sodium, calcium, iPTH, hemoglobin, platelets, and leukocytes. HR, hazard ratio; CI, confidence interval; COVID-19, coronavirus disease 2019; IDWG, interdialytic weight gain; OCM, online clearance monitoring; iPTH, intact parathyroid hormone