Skip to main content
Top
Published in: Journal of Nephrology 1/2017

Open Access 01-02-2017 | Original Article

Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment

Authors: Johan Vande Walle, Yahsou Delmas, Gianluigi Ardissino, Jimmy Wang, John F. Kincaid, Herman Haller

Published in: Journal of Nephrology | Issue 1/2017

Login to get access

Abstract

Background

Eculizumab is approved for atypical hemolytic uremic syndrome (aHUS). Guidelines discuss the importance of prompt treatment. We report a post hoc analysis investigating the effect of baseline factors, including patient characteristics and time from the latest aHUS manifestation to eculizumab initiation, on change from baseline in estimated glomerular filtration rate (eGFR) and other outcomes.

Methods

Data were pooled from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for patients with aHUS. Multivariate regressions identified predictors of eGFR change from baseline. The proportion of patients achieving sustained eGFR increase (defined: ≥15 ml/min/1.73 m2 for ≥28 days) and platelet count normalization were evaluated 1 year post-treatment. Baseline characteristics and eGFR outcomes were summarized by time to treatment from last aHUS manifestation [≤7 days (n = 21) versus >7 days (n = 76)].

Results

Baseline eGFR were similar between groups. Multivariate regression analysis demonstrated time from aHUS manifestation to eculizumab treatment, age, baseline lactate dehydrogenase (LDH) and baseline hemoglobin were independently predictive of eGFR change from baseline. Mean eGFR change from baseline at 1 year was significantly higher in patients treated in ≤7 days than >7 days (57 vs. 23 ml/min/1.73 m2, p = 0.0098). After 1 year, 17/21 and 36/76 patients in the ≤7 and >7 day groups, respectively, achieved a sustained increase in eGFR. Mean time to platelet count normalization was similar between groups.

Conclusions

Younger age, higher baseline LDH and lower baseline hemoglobin were associated with greater eGFR improvements. Early eculizumab initiation led to improved renal recovery, demonstrating the importance of rapid diagnosis and treatment of patients with aHUS.
Appendix
Available only for authorised users
Literature
3.
go back to reference Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyo JM, Praga M, Torra R, Vilalta R, Rodriguez de Cordoba S (2013) An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 33:27–45. doi:10.3265/Nefrologia.pre2012.Nov.11781 PubMed Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyo JM, Praga M, Torra R, Vilalta R, Rodriguez de Cordoba S (2013) An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 33:27–45. doi:10.​3265/​Nefrologia.​pre2012.​Nov.​11781 PubMed
4.
go back to reference Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschenes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562. doi:10.2215/CJN.04760512 CrossRefPubMedPubMedCentral Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschenes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562. doi:10.​2215/​CJN.​04760512 CrossRefPubMedPubMedCentral
5.
go back to reference Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859. doi:10.2215/CJN.02210310 CrossRefPubMedPubMedCentral Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859. doi:10.​2215/​CJN.​02210310 CrossRefPubMedPubMedCentral
7.
go back to reference Lech M, Grobmayr R, Ryu M, Lorenz G, Hartter I, Mulay SR, Susanti HE, Kobayashi KS, Flavell RA, Anders HJ (2014) Macrophage phenotype controls long-term AKI outcomes–kidney regeneration versus atrophy. J Am Soc Nephrol 25:292–304. doi:10.1681/ASN.2013020152 CrossRefPubMed Lech M, Grobmayr R, Ryu M, Lorenz G, Hartter I, Mulay SR, Susanti HE, Kobayashi KS, Flavell RA, Anders HJ (2014) Macrophage phenotype controls long-term AKI outcomes–kidney regeneration versus atrophy. J Am Soc Nephrol 25:292–304. doi:10.​1681/​ASN.​2013020152 CrossRefPubMed
8.
go back to reference Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, Mele C, Bresin E, Cassis L, Gamba S, Porrati F, Bucchioni S, Monteferrante G, Fang CJ, Liszewski MK, Kavanagh D, Atkinson JP, Remuzzi G, International Registry of R, Familial HT (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 108:1267–1279. doi:10.1182/blood-2005-10-007252 CrossRef Caprioli J, Noris M, Brioschi S, Pianetti G, Castelletti F, Bettinaglio P, Mele C, Bresin E, Cassis L, Gamba S, Porrati F, Bucchioni S, Monteferrante G, Fang CJ, Liszewski MK, Kavanagh D, Atkinson JP, Remuzzi G, International Registry of R, Familial HT (2006) Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 108:1267–1279. doi:10.​1182/​blood-2005-10-007252 CrossRef
9.
go back to reference Zuber J, Fakhouri F, Roumenina LT, Loirat C, Fremeaux-Bacchi V, French Study Group for a HCG (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657. doi:10.1038/nrneph.2012.214 Zuber J, Fakhouri F, Roumenina LT, Loirat C, Fremeaux-Bacchi V, French Study Group for a HCG (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657. doi:10.​1038/​nrneph.​2012.​214
10.
go back to reference Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181. doi:10.1056/NEJMoa1208981 CrossRefPubMed Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181. doi:10.​1056/​NEJMoa1208981 CrossRefPubMed
11.
go back to reference Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen DJ, Delmas Y, Douglas K, Furman RR, Gaber OA, Goodship T, Herthelius M, Hourmant M, Legendre CM, Remuzzi G, Sheerin N, Trivelli A, Loirat C (2015) Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int 87:1061–1073. doi:10.1038/ki.2014.423 CrossRefPubMedPubMedCentral Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen DJ, Delmas Y, Douglas K, Furman RR, Gaber OA, Goodship T, Herthelius M, Hourmant M, Legendre CM, Remuzzi G, Sheerin N, Trivelli A, Loirat C (2015) Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int 87:1061–1073. doi:10.​1038/​ki.​2014.​423 CrossRefPubMedPubMedCentral
12.
go back to reference Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Fremeaux-Bacchi V, for HUSI (2015) An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. doi:10.1007/s00467-015-3076-8 PubMed Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Fremeaux-Bacchi V, for HUSI (2015) An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. doi:10.​1007/​s00467-015-3076-8 PubMed
13.
go back to reference Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB, European Paediatric Study Group for HUS (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696. doi:10.1007/s00467-008-0964-1 CrossRef Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB, European Paediatric Study Group for HUS (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696. doi:10.​1007/​s00467-008-0964-1 CrossRef
14.
go back to reference Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, Himmelfarb J, Collins AJ (2006) Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 17:1135–1142. doi:10.1681/ASN.2005060668 CrossRefPubMed Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, Himmelfarb J, Collins AJ (2006) Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 17:1135–1142. doi:10.​1681/​ASN.​2005060668 CrossRefPubMed
Metadata
Title
Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment
Authors
Johan Vande Walle
Yahsou Delmas
Gianluigi Ardissino
Jimmy Wang
John F. Kincaid
Herman Haller
Publication date
01-02-2017
Publisher
Springer International Publishing
Published in
Journal of Nephrology / Issue 1/2017
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-016-0288-3

Other articles of this Issue 1/2017

Journal of Nephrology 1/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.