Dataset Information

Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter.

ABSTRACT:

Introduction

Among kidney transplant recipients (KTRs) with end-stage kidney disease (ESKD) due to atypical hemolytic uremic syndrome (aHUS), recurrence is associated with poor allograft outcomes. We compared graft and patient survival of aHUS KTRs with and without prophylactic/early use of eculizumab, a monoclonal antibody that binds complement protein C5, at the time of transplantation.

Methods

We conducted a retrospective cohort study using the United States Renal Data System. Out of 123 624 ESKD patients transplanted between January 1, 2008, and June 1, 2016, we identified 348 (0.28%) patients who had "hemolytic uremic syndrome" as the primary cause of ESKD. We then linked these patients to datasets containing the Healthcare Common Procedure Coding System (HCPCS) code for eculizumab infusion. Patients who received eculizumab prior to or within 30 days of transplant represented the exposure group. We calculated crude incidence rates and conducted exact logistic regression, adjusted for recipient age and sex, for the study outcomes of graft loss, death-censored graft loss, and mortality. We also estimated the average treatment effect (ATE) by propensity-score matching, to reduce the bias in the estimated treatment effect on graft loss.

Results

Our final study cohort included 335 aHUS KTRs (23 received eculizumab, 312 did not), with a mean duration of follow-up of 5.8 ± 2.7 years. There were no significant differences in baseline demographic and clinical characteristics between the eculizumab versus non-eculizumab group. Patients who received prophylactic/early eculizumab were less likely to experience graft loss compared with those who did not receive eculizumab (0% vs 20%, P = .02), with an adjusted odds ratio of 0.13 (P = .02). In the propensity-score-matched sample, the ATE (eculizumab vs non-eculizumab) was -0.20 (95% confidence interval [CI] = -0.25 to -0.15, P < .001); thus, treatment was associated with an average of 20% reduction in graft loss. There was no significant difference in the risk of death between the 2 groups.

Conclusions

Although there was no significant difference in the risk of death, prophylactic/early use of eculizumab was significantly associated with improved graft survival among aHUS KTRs. Given the high cost of eculizumab, randomized controlled trials are much needed to guide prophylactic strategies to prevent graft loss.

SUBMITTER: Plasse RA

PROVIDER: S-EPMC8020226 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8-13.4%, I2 = 0%) and 5.5% (95%CI: 2.9-10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6-34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2-36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger's regression asymmetry test (p > 0.05 for all analyses). This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS.