Academic Journal
A systematic review of short-term outcomes in patients with anti-factor H associated atypical HUS managed with plasma exchanges versus eculizumab.
| Τίτλος: | A systematic review of short-term outcomes in patients with anti-factor H associated atypical HUS managed with plasma exchanges versus eculizumab. |
|---|---|
| Συγγραφείς: | Sinha A; Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India., Bindal T; Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India., Zotta F; Division of Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Sellier-Leclerc AL; Department of Pediatric Nephrology, Centre de Référence Des Maladies Rénales Rares Néphrogones, Filières Maladies Rares ORKID Et ERK-Net, CHU de Lyon, Bron, France., Hogan J; Department of Pediatric Nephrology, Reference Center for Thrombotic Microangiopathies, Rare Disease Networks ORKID and ERK-Net, Robert Debré Hospital, APHP, Paris Cité University, Paris, France., Hari P; Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India., Vivarelli M; Division of Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.; Clinical Trial Center and Laboratory of Nephrology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Bagga A; Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. arvindbagga@hotmail.com.; Department of Pediatrics, Indraprastha Apollo Hospitals, New Delhi, India. arvindbagga@hotmail.com. |
| Πηγή: | Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2026 Dec; Vol. 41 (12), pp. 4369-4378. Date of Electronic Publication: 2026 May 08. |
| Τύπος έκδοσης: | Journal Article; Systematic Review; Comparative Study; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer International Country of Publication: Germany NLM ID: 8708728 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-198X (Electronic) Linking ISSN: 0931041X NLM ISO Abbreviation: Pediatr Nephrol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Berlin : Springer International Original Publication: Berlin : Springer International, c1987- |
| Ιατρικοί όροι (MeSH): | Atypical Hemolytic Uremic Syndrome*/therapy , Atypical Hemolytic Uremic Syndrome*/immunology , Antibodies, Monoclonal, Humanized*/therapeutic use , Plasma Exchange*/methods , Complement Factor H*/immunology , Complement Inactivating Agents*/therapeutic use, Combined Modality Therapy/methods ; Immunosuppressive Agents/therapeutic use ; Humans ; Treatment Outcome ; Child ; Remission Induction ; Time Factors |
| Περίληψη: | Background: Antibodies to factor H (anti-FH) are a leading cause of atypical hemolytic uremic syndrome (aHUS) in school-going children. While terminal complement blockade with eculizumab (ECZ) is standard of care for all forms of aHUS, anti-FH associated aHUS is uniquely amenable to combination therapy with plasma exchange (PEX) and immunosuppression. There are no controlled comparisons on the relative short- or medium-term efficacy of the two strategies of management. Objectives: The primary objectives were to compare the time from initiation of therapy to hematological remission and renal recovery between patients managed with PEX versus ECZ, with or without immunosuppression, for anti-FH associated aHUS in native kidneys. We also compared the proportions of patients attaining hematological remission or renal recovery by 7, 14 and 28 days of therapy, and proportion of patients with chronic kidney disease G1-5, dialysis-dependence, or death. Data Sources: PubMed and Embase were searched from January 2004 to April 2025. Study Eligibility Criteria: Studies, in English language, were eligible if they reported the time to hematological remission and renal recovery in individual patients with anti-FH antibody-associated aHUS in native kidneys and treated with either PEX or ECZ with or without additional immunosuppression. Participants and Interventions: Within studies, individual patients were included if they had received either, and not both, PEX or ECZ, and information regarding time to hematological remission and renal recovery was available. Study Appraisal and Synthesis Methods: The risk of bias for retrospective cohort studies and case reports or series was assessed using the Newcastle-Ottawa Quality Assessment Scale and Joanna Briggs Institute (JBI) tool for systematic reviews, respectively. Individual patient data were combined by therapy group to report time-to-event outcomes as hazard ratios (95% confidence intervals, CI), compared using the log rank test. Other continuous measures were compared between groups using the rank sum test. Results: Fourteen of 57 studies shortlisted from among 403 search results met eligibility criteria, within which 99 patients, including 81 managed with PEX and 18 with ECZ, with/without immunosuppression, were eligible. Patients receiving PEX presented later with more severe anemia and lower eGFR, and more often required dialysis. Median time to hematologic remission was significantly shorter with PEX (9 vs. 20 days; P = 0.0007) while time to renal recovery was similar (16 vs. 20 days; P = 0.36). The proportion with CKD G3-5 and mortality was insignificantly higher with PEX than ECZ (respective P 0.077 and 0.36). Limitations: Our findings are limited by small numbers of participants and studies, lack of comparative studies, heterogeneity in disease severity, and variations in definitions of outcomes. Conclusions and Implications of Key Findings: Patients managed with PEX achieved hematological remission faster than those on ECZ; the time to renal recovery was similar. Given the precautions and vigilance necessary with complement blockade, PEX appears to be a satisfactory initial choice for managing anti-FH associated HUS, particularly in low-resource settings. Prospective trials should compare the efficacy, safety and healthcare costs of these strategies in managing patients with anti-FH associated HUS. Systematic Review Registration Number: PROSPERO ID: CRD420251033150. (© 2026. The Author(s), under exclusive licence to International Pediatric Nephrology Association.) |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. |
| References: | Michael M, Bagga A, Sartain SE, Smith RJH (2022) Haemolytic uraemic syndrome. Lancet 400:1722–1740. (PMID: 10.1016/S0140-6736(22)01202-836272423) Raina R, Sethi SK, Dragon-Durey MA, Khooblall A, Sharma D, Khandelwal P, Shapiro R, Boyer O, Yap HK, Bagga A, Licht C (2022) Systematic review of atypical hemolytic uremic syndrome biomarkers. Pediatr Nephrol 37:1479–1493. https://doi.org/10.1007/s00467-022-05451-2. (PMID: 10.1007/s00467-022-05451-235118546) Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, Saini H, Kotresh ST, Ali U, Bhatia D, Ohri A, Kumar M, Agarwal I, Gulati S, Anand K, Vijayakumar M, Sinha R, Sethi S, Salmona M, George A, Bal V, Singh G, Dinda AK, Hari P, Rath S, Dragon-Durey MA, Bagga A, Indian HUS Registry (2014) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 85:1151–1160. https://doi.org/10.1038/ki.2013.373. (PMID: 10.1038/ki.2013.37324088957) Bagga A, Khandelwal P, Mishra K, Thergaonkar R, Vasudevan A, Sharma J, Patnaik SK, Sinha A, Sethi S, Hari P, Dragon-Durey MA, Indian Society of Pediatric Nephrology (2019) Hemolytic uremic syndrome in a developing country: Consensus guidelines. Pediatr Nephrol 34:1465–1482. https://doi.org/10.1007/s00467-019-04233-7. (PMID: 10.1007/s00467-019-04233-730989342) Ferri M, Zotta F, Donadelli R, Dossier C, Duneton C, El-Sissy C, Fremeau-Bacchi V, Kwon T, Quadri L, Pasini A, Sellier-Leclerc AL, Vivarelli M, Hogan J (2024) Anti-CFH-associated hemolytic uremic syndrome: Do we still need plasma exchange? Pediatr Nephrol 39:3263–3269. https://doi.org/10.1007/s00467-024-06373-x. (PMID: 10.1007/s00467-024-06373-x38632123) Kavanagh D, Ardissino G, Brocklebank V, Bouwmeester RN, Bagga A, Ter Heine R, Johnson S, Licht C, Ma ALT, Noris M, Praga M, Rondeau E, Sinha A, Smith RJH, Sheerin NS, Trimarchi H, Wetzels JFM, Vivarelli M, Van de Kar NCAJ, Greenbaum LA, Forum Participants (2024) Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int 106:1038–1050. https://doi.org/10.1016/j.kint.2024.09.012. (PMID: 10.1016/j.kint.2024.09.0123939562812365746) Puraswani M, Khandelwal P, Saini H, Saini S, Gurjar BS, Sinha A, Shende RP, Maiti TK, Singh AK, Kanga U, Ali U, Agarwal I, Anand K, Prasad N, Rajendran P, Sinha R, Vasudevan A, Saxena A, Agarwal S, Hari P, Sahu A, Rath S, Bagga A (2019) Clinical and immunological profile of anti-factor H antibody associated atypical hemolytic uremic syndrome: A nationwide database. Front Immunol 10:1282. (PMID: 10.3389/fimmu.2019.01282312313916567923) Bindal T, Sinha A, Bagga A (2025) Eculizumab for atypical hemolytic uremic syndrome: Guidance for developing countries. Indian J Nephrol 35:466–475. https://doi.org/10.25259/IJN_140_2025. (PMID: 10.25259/IJN_140_2025) Thangaraju S, Khandelwal P, Mishra K, Kumar M, Puraswani M, Saini R, Hari P, Coshic P, Sinha A, Bagga A (2024) Abbreviated protocol of plasma exchanges for patients with anti-factor H associated hemolytic uremic syndrome. Pediatr Nephrol 39:2091–2097. https://doi.org/10.1007/s00467-024-06279-8. (PMID: 10.1007/s00467-024-06279-838270601) Tiewsoh K, Govindarajan S, Dawman L, Rawat A, Ramachandran R, Hans R (2021) Anti-compliment factor H antibody associated hemolytic uremic syndrome in children with abbreviated plasma exchanges: A 12-month follow-up study. Iran J Kidney Dis 15:419–425. https://doi.org/10.52547/ijkd.6507. (PMID: 10.52547/ijkd.650734930853) Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med 18:e1003583. https://doi.org/10.1371/journal.pmed.1003583. (PMID: 10.1371/journal.pmed.1003583337804388007028) Wells GA, Wells G, Shea B, Shea B, O'Connell D, Peterson J, Welch J, Losos M, Tugwell P, Ga SW, Zello GA, Petersen JA (2014) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed 1 Jan 2026. Munn Z, Stone JC, Aromataris E, Klugar M, Sears K, Leonardi-Bee J, Barker TH (2023) Assessing the risk of bias of quantitative analytical studies: Introducing the vision for critical appraisal within JBI systematic reviews. JBI Evid Synth 21:467–471. https://doi.org/10.11124/JBIES-22-00224. (PMID: 10.11124/JBIES-22-0022436476419) Khandelwal P, Thomas CC, Rathi BS, Hari P, Tiwari AN, Sinha A, Bagga A (2019) Membrane-filtration based plasma exchanges for atypical hemolytic uremic syndrome: Audit of efficacy and safety. J Clin Apher 34:555–562. https://doi.org/10.1002/jca.21711. (PMID: 10.1002/jca.2171131173399) Noone D, Waters A, Pluthero FG, Geary DF, Kirschfink M, Zipfel PF, Licht C (2014) Successful treatment of DEAP-HUS with eculizumab. Pediatr Nephrol 29:841–851. https://doi.org/10.1007/s00467-013-2654-x. (PMID: 10.1007/s00467-013-2654-x24249282) Kise T, Fukuyama S, Uehara M (2020) Successful treatment of anti-factor H antibody-associated atypical hemolytic uremic syndrome. Indian J Nephrol 30:35–38. https://doi.org/10.4103/ijn.IJN_336_18. (PMID: 10.4103/ijn.IJN_336_1832015599) Blanc C, Roumenina LT, Ashraf Y, Hyvärinen S, Sethi SK, Ranchin B, Niaudet P, Loirat C, Gulati A, Bagga A, Fridman WH, Sautès-Fridman C, Jokiranta TS, Frémeaux-Bacchi V, Dragon-Durey MA (2012) Overall neutralization of complement factor H by autoantibodies in the acute phase of the autoimmune form of atypical hemolytic uremic syndrome. J Immunol 189:3528–3537. https://doi.org/10.4049/jimmunol.1200679. (PMID: 10.4049/jimmunol.120067922922817) Wijnsma KL, Ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, van den Heuvel LP, Wetzels JFM, van de Kar NCAJ, Brüggemann RJ (2019) Pharmacology, pharmacokinetics and pharmacodynamics of eculizumab, and possibilities for an individualized approach to eculizumab. Clin Pharmacokinet 58:859–874. https://doi.org/10.1007/s40262-019-00742-8. (PMID: 10.1007/s40262-019-00742-8307587366584251) Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar NC, Vande Walle J, Ogawa M, Bedrosian CL, Licht C (2016) Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 89:701–711. https://doi.org/10.1016/j.kint.2015.11.026. (PMID: 10.1016/j.kint.2015.11.02626880462) Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, Menne J, Minetti EE, Provôt F, Rondeau E, Ruggenenti P, Weekers LE, Ogawa M, Bedrosian CL, Legendre CM (2016) Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: A single-arm, open-label trial. Am J Kidney Dis 68:84–93. https://doi.org/10.1053/j.ajkd.2015.12.034. (PMID: 10.1053/j.ajkd.2015.12.03427012908) Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Frieling M, Karpman D, Landau D, Langman C, Licht C, Pecoraro C, Riedl M, Siomou E, van de Kar N, Walle JV, Loirat C, Taylor CM (2014) An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol 29:1967–1978. https://doi.org/10.1007/s00467-014-2817-4. (PMID: 10.1007/s00467-014-2817-424817340) |
| Grant Information: | 5/7/1090/2013-RHN Indian Council of Medical Research; IIRPIG-2023-0000119 Indian Council of Medical Research |
| Contributed Indexing: | Keywords: Autoimmune HUS; Complement blockade; DEAP-HUS |
| Substance Nomenclature: | A3ULP0F556 (eculizumab) 0 (Antibodies, Monoclonal, Humanized) 80295-65-4 (Complement Factor H) 0 (Complement Inactivating Agents) 0 (Immunosuppressive Agents) 0 (CFH protein, human) |
| Entry Date(s): | Date Created: 20260508 Date Completed: 20261015 Latest Revision: 20261015 |
| Update Code: | 20261016 |
| DOI: | 10.1007/s00467-026-07309-3 |
| PMID: | 42101481 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1432-198X |
|---|---|
| DOI: | 10.1007/s00467-026-07309-3 |