Document Detail

Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria.
MedLine Citation:
PMID:  20658586     Owner:  NLM     Status:  MEDLINE    
Paroxysmal nocturnal hemoglobinuria (PNH) is a debilitating and life-threatening disease in which lysis of PNH red blood cells frequently manifests with chronic hemolysis, anemia, and thrombosis. Renal damage in PNH is associated with chronic hemosiderosis and/or microvascular thrombosis. We determined the incidence of renal dysfunction or damage, defined by stages of chronic kidney disease (CKD), in a large cohort of PNH patients and evaluated the safety and efficacy of the complement inhibitor eculizumab in altering its progression. Renal dysfunction or damage was observed in 65% of the study population at baseline with 21% of patients with later stage CKD or kidney failure (glomerular filtration rate [GFR] <or=60 ml/min/1.73 m(2); Stage 3, 4, or 5). Eculizumab treatment was safe and well-tolerated in patients with renal dysfunction or damage and resulted in the likelihood of improvement as defined as categorical reduction in CKD stage (P < 0.001) compared with baseline and to placebo (P = 0.04). Improvement in renal function was more commonly seen in patients with baseline CKD Stages 1-2 (67.1% improvement, P < 0.001) although improvement was also observed in patients with CKD Stages 3-4 (P = 0.05). Improvements occurred quickly and were sustained for at least 18 months of treatment. Patients categorized at CKD Stages 3-5 did not worsen during treatment with eculizumab. Overall, 40 (21%) of 195 patients who demonstrated renal dysfunction or damage at baseline were no longer classified as such after 18 months of treatment. Administration of eculizumab to patients with renal dysfunction or damage was well tolerated and was usually associated with clinical improvement.
Peter Hillmen; Modupe Elebute; Richard Kelly; Alvaro Urbano-Ispizua; Anita Hill; Russell P Rother; Gus Khursigara; Chieh-Lin Fu; Mitsuhiro Omine; Paul Browne; Wendell Rosse
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Publication Detail:
Type:  Clinical Trial, Phase II; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial    
Journal Detail:
Title:  American journal of hematology     Volume:  85     ISSN:  1096-8652     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-08-11     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-9     Citation Subset:  IM    
Copyright Information:
(c) 2010 Wiley-Liss, Inc.
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MeSH Terms
Aged, 80 and over
Antibodies, Monoclonal / pharmacology,  therapeutic use*
Antibodies, Monoclonal, Humanized
Complement Activation / drug effects
Complement C5 / antagonists & inhibitors*,  immunology
Complement Inactivating Agents / therapeutic use*
Glomerular Filtration Rate / drug effects
Hemoglobinuria, Paroxysmal / complications,  drug therapy*,  immunology,  physiopathology
Hemolysis / drug effects
Kidney / drug effects,  physiopathology*
Kidney Failure, Chronic / drug therapy,  etiology,  physiopathology,  prevention & control*
Metabolic Clearance Rate / drug effects
Middle Aged
Pilot Projects
Severity of Illness Index
Treatment Outcome
Young Adult
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Complement C5; 0/Complement Inactivating Agents; A3ULP0F556/eculizumab
Comment In:
Am J Hematol. 2010 Aug;85(8):551-2   [PMID:  20658585 ]
Erratum In:
Am J Hematol. 2010 Nov;85(11):911

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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