Javier Varas

Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study

Background: The majority of studies suggesting that online hemodiafiltration reduces the risk of mortality compared to hemodialysis (HD) have been performed in dialysis-prevalent populations. In this report, we conducted an epidemiologic study of mortality in incident dialysis patients, comparing post-dilution online hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to correct indication bias. Methods: Our study cohort comprised 3,075 incident dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between January 2009 and December 2012. The primary outcome of this study was to investigate the impact of the type of renal replacement on all-cause mortality. An analysis of cardiovascular mortality was defined as the secondary outcome. To achieve these objectives, patients were followed until December 2016. Patients were categorized as high-flux HD patients if they underwent this treatment exclusively. If >90% of their treatment was with online hemodiafiltration, then the patient was grouped to that modality. Results: After PSM, a total of 1,012 patients were matched. Compared with patients on high-flux HD, those on online hemodiafiltration received a median replacement volume of 23.45 (interquartile range 21.27–25.51) L/session and manifested 24 and 33% reductions in all-cause and cardiovascular mortality (all-cause mortality hazards ratio [HR] 0.76, 95% CI 0.62–0.94 [p = 0.01]; and cardiovascular mortality HR 0.67, 95% CI 0.50–0.90 [p = 0.008]). Conclusions: This study shows that post-dilution online hemodiafiltration reduces all-cause and cardiovascular mortality compared to high-flux HD in an incident HD population.

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach

Background Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. Methods This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Results Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses  >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Conclusions Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations.

Increased mortality in haemodialysis patients administered high doses of erythropoiesis-stimulating agents: a propensity score-matched analysis

Background Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure. Methods A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA administration was according to standard medical practice. Patients were grouped as quintiles, according to ESA dose, in order to compare mortality and hospitalization data. Using propensity score matching (PSM), we defined two groups of 324 patients receiving weekly threshold ESA doses of either > or ≤8000 IU. Results Kaplan-Meier survival curves indicated significant increases in the risk of mortality in patients administered with high doses of ESAs (>8127.4 IU/week). Multivariate Cox models identified a high ESA dose as an independent predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic regression models identified high ESA doses as an independent predictor for all-cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA doses of >8000 IU constitute an independent predictor of all-cause mortality and hospitalization, even though the adjusted cohort displayed the same demographic features, inflammatory profile, clinical HD parameters and haemoglobin levels. Conclusions Our data suggest that ESA doses of >8000 IU/week are associated with an increased risk of all-cause mortality and hospitalization in HD patients.

Returning to haemodialysis after kidney allograft failure: a survival study with propensity score matching

BACKGROUND Patients who return to dialysis after kidney allograft failure (KAF) are classically considered to have lower survival rates than their transplant-naïve incident dialysis counterparts. However, this observation in previous comparisons could be due to poor matching between the two populations. METHODS To compare survival rates between patients who returned to haemodialysis (HD) after KAF versus transplant-naïve incident HD patients, we performed a retrospective study using the EuCliD® database (European Clinical Database) that collects data from Fresenius Medical Care (FMC) outpatient HD facilities in Spain. Propensity score matching (PSM) was performed to homogenize both populations. RESULTS This study included 5216 patients from 65 different FMC clinics between 2009 and 2014. Naïve incident HD patients were mostly male, older, comorbid and more commonly had catheters as vascular access. During the study follow-up, 3915 patients exited, of whom 1534 died. The mean survival time for the entire cohort was 4.86 years [95% confidence interval (CI) 4.78-4.94]. Univariate Cox analysis indicated higher mortality risk among transplant-naïve incident HD patients [hazard ratio (HR) 1.728; 95% CI 1.35-2.21; P < 0.001). However, this difference was no longer significant after multivariate adjustment. After applying PSM to minimize the bias due to indication issue, we obtained an adjusted population composed of 480 naïve and 240 KAF patients. The results analysing the PSM-adjusted cohort confirmed similar survival in both cohorts (log-rank, 3.34; P = 0.068; HR 1.382; 95% CI 0.97-1.95; P = 0.069). CONCLUSIONS When comparing properly matched patient groups, patients who return to HD after KAF present similar survival than survival than transplant-naïve incident patients.

Proton Pump Inhibitor Usage and the Risk of Mortality in Hemodialysis Patients

Introduction Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. Methods We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score–matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. Results PPI use was associated with hypomagnesemia (Mg <1.8 mg/dl (0.75 mmol/l); odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.38−5.27, P < 0.01). The exposure to PPIs in the full patient cohort was identified as an independent predictor for all-cause mortality in both univariate (HR = 3.16, 95% CI = 1.69–5.90, P < 0.01) and multivariate (HR = 2.70, 95% CI = 1.38–5.27, P < 0.01) Cox regression models. Moreover PPI use was identified as a predictor of CV mortality (HR = 1.51, 95% CI = 1.05−2.20, P = 0.03) Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR = 1.412, 95% CI = 1.04–1.93, P = 0.03) and CV mortality (HR = 1.67, 95% CI = 1.03−2.71, P = 0.04) were higher among patients on PPIs versus those not on PPIs. Conclusion The study data suggest that the PPI treatment should be regularly monitored and prescribed only when indicated.

The Combination of Beta Blockers and Renin-Angiotensin System Blockers Improves Survival in Incident Hemodialysis Patients: A Propensity-Matched Study

Introduction Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis. Methods We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04–3.34 yr). Results After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker–based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05–2.69; ß-blocker: HR: 1.59; 95% CI: 1.01–2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08–2.58). Discussion Our data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.