Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter
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 eculizu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2021-03-01
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| Series: | Canadian Journal of Kidney Health and Disease |
| Online Access: | https://doi.org/10.1177/20543581211003763 |
| _version_ | 1819276383956762624 |
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| author | Richard A. Plasse Stephen W. Olson Christina M. Yuan Lawrence Y. Agodoa Kevin C. Abbott Robert Nee |
| author_facet | Richard A. Plasse Stephen W. Olson Christina M. Yuan Lawrence Y. Agodoa Kevin C. Abbott Robert Nee |
| author_sort | Richard A. Plasse |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T23:39:21Z |
| format | Article |
| id | doaj.art-0ea7a77125154d0fbff7d71d203e9f7a |
| institution | Directory Open Access Journal |
| issn | 2054-3581 |
| language | English |
| last_indexed | 2024-12-23T23:39:21Z |
| publishDate | 2021-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Canadian Journal of Kidney Health and Disease |
| spelling | doaj.art-0ea7a77125154d0fbff7d71d203e9f7a2022-12-21T17:25:45ZengSAGE PublishingCanadian Journal of Kidney Health and Disease2054-35812021-03-01810.1177/20543581211003763Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research LetterRichard A. Plasse0Stephen W. Olson1Christina M. Yuan2Lawrence Y. Agodoa3Kevin C. Abbott4Robert Nee5Department of Medicine, Uniformed Services University, Bethesda, MD, USADepartment of Medicine, Uniformed Services University, Bethesda, MD, USADepartment of Medicine, Uniformed Services University, Bethesda, MD, USAOffice of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USADivision of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USADepartment of Medicine, Uniformed Services University, Bethesda, MD, USAIntroduction: 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.https://doi.org/10.1177/20543581211003763 |
| spellingShingle | Richard A. Plasse Stephen W. Olson Christina M. Yuan Lawrence Y. Agodoa Kevin C. Abbott Robert Nee Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter Canadian Journal of Kidney Health and Disease |
| title | Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter |
| title_full | Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter |
| title_fullStr | Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter |
| title_full_unstemmed | Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter |
| title_short | Prophylactic or Early Use of Eculizumab and Graft Survival in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome in the United States: Research Letter |
| title_sort | prophylactic or early use of eculizumab and graft survival in kidney transplant recipients with atypical hemolytic uremic syndrome in the united states research letter |
| url | https://doi.org/10.1177/20543581211003763 |
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