Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome


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Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome
J Am Soc Nephrol
Zuber J., Frimat M., Caillard S., Kamar N., Gatault P., Petitprez F., Couzi L., Jourde-Chiche N., Chatelet V., Gaisne R., Bertrand D., Bamoulid J., Louis M., Sberro Soussan R., Navarro D., Westeel P. F., Frimat L., Colosio C., Thierry A., Rivalan J., Albano L., Arzouk N., Cornec-Le Gall E., Claisse G., Elias M., El Karoui K., Chauvet S., Coindre J. P., Rerolle J. P., Tricot L., Sayegh J., Garrouste C., Charasse C., Delmas Y., Massy Z., Hourmant M., Servais A., Loirat C., Fakhouri F., Pouteil-Noble C., Peraldi M. N., Legendre C., Rondeau E., Le Quintrec M., Fremeaux-Bacchi V.
1533-3450 (Electronic)
Publication state
Issued date
Zuber, Julien
Frimat, Marie
Caillard, Sophie
Kamar, Nassim
Gatault, Philippe
Petitprez, Florent
Couzi, Lionel
Jourde-Chiche, Noemie
Chatelet, Valerie
Gaisne, Raphael
Bertrand, Dominique
Bamoulid, Jamal
Louis, Magali
Sberro Soussan, Rebecca
Navarro, David
Westeel, Pierre-Francois
Frimat, Luc
Colosio, Charlotte
Thierry, Antoine
Rivalan, Joseph
Albano, Laetitia
Arzouk, Nadia
Cornec-Le Gall, Emilie
Claisse, Guillaume
Elias, Michelle
El Karoui, Khalil
Chauvet, Sophie
Coindre, Jean-Philippe
Rerolle, Jean-Philippe
Tricot, Leila
Sayegh, Johnny
Garrouste, Cyril
Charasse, Christophe
Delmas, Yahsou
Massy, Ziad
Hourmant, Maryvonne
Servais, Aude
Loirat, Chantal
Fakhouri, Fadi
Pouteil-Noble, Claire
Peraldi, Marie-Noelle
Legendre, Christophe
Rondeau, Eric
Le Quintrec, Moglie
Fremeaux-Bacchi, Veronique
Observational Study
Research Support, Non-U.S. Gov't
J Am Soc Nephrol. 2019 Dec;30(12):2449-2463. doi: 10.1681/ASN.2019040331. Epub 2019 Oct 1.
BACKGROUND: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. METHODS: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. RESULTS: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. CONCLUSIONS: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
Adult, Antibodies, Monoclonal, Humanized/*therapeutic use, Atypical Hemolytic Uremic Syndrome/*drug therapy/epidemiology/genetics/surgery, Complement C3b Inactivator Proteins/genetics, Complement Inactivating Agents/*therapeutic use, Complement System Proteins/analysis, Female, France, Graft Survival/drug effects, Humans, Kaplan-Meier Estimate, *Kidney Transplantation, Male, Middle Aged, Mutant Chimeric Proteins/genetics, Preoperative Care, Proportional Hazards Models, Recurrence, Registries, Retrospective Studies, Secondary Prevention, *complement, *hemolytic uremic syndrome
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01/03/2022 11:17
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02/03/2022 7:36
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