Clinical features and HLA association of 5-Aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease.

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Authors
Heap, Graham A.
So, K
Weedon, M
Edney, Naomi
Bewshea, Claire
Singh, Abhey
Annese, V
Beckly, J
Buurman, D
Chaudhary, R
Journal
Journal of Crohn's & Colitis
Type
Journal Article
Publisher
Oxford University Press
Rights
Archived with thanks to Journal of Crohn's & colitis
Background & AimsNephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so these drugs can be avoided, or monitoring intensified, in high-risk patients.MethodsInflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome wide association study was then undertaken with these cases and 4,109 disease controls.ResultsAfter adjudication, 151 cases of 5-ASA induced nephrotoxicity were identified. 68% of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% CI 2.3 - 3.7). Only 30% of cases recovered completely after drug withdrawal with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (P=1x10(-7)) with 5-ASA induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n=55) significantly strengthened this association (P=4x10(-9), Odds Ratio 3.1).ConclusionsThis is the largest and most detailed study of 5-ASA induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to a drug induced renal injury.
Citation
Clinical features and HLA association of 5-Aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease. 2016 Feb;10(2):149-58
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