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

4.00
Hdl Handle:
http://hdl.handle.net/11287/592562
Title:
Clinical features and HLA association of 5-Aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease.
Authors:
Heap, Graham A; So, K; Weedon, M; Edney, Naomi; Bewshea, Claire; Singh, Abhey; Annese, V; Beckly, J; Buurman, D; Chaudhary, R; Cole, A T; Cooper, S C; Creed, T; Cummings, F; de Boer, N K; D'Inca, R; D'Souza, Richard; Daneshmend, T K; Delaney, M; Dhar, A; Direkze, N; Dunckley, P; Gaya, D R; Gearry, R; Gore, S; Halfvarsson, J; Hart, A; Hawkey, C J; Hoentjen, F; Iqbal, T; Irving, P; Lal, S; Lawrance, I; Lees, C W; Lewis, S; Lockett, M; Mann, S; Mansfield, J; Mowat, C; Mulgrew, Chris J; Muller, F; Murray, C; Oram, Richard; Orchard, T; Parkes, M; Phillips, R; Pollok, R; Radford-Smith, G; Sebastian, S; Sen, S; Shirazi, T; Silverberg, M; Solomon, L; Sturniolo, G C; Thomas, M; Tremelling, M; Tsianos, E V; Watts, D; Weaver, S; Weersma, R K; Wesley, E; Holden, Ar; Ahmad, Tariq
Abstract:
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
Publisher:
Oxford University Press
Journal:
Journal of Crohn's & Colitis
Issue Date:
29-Nov-2015
URI:
http://hdl.handle.net/11287/592562
DOI:
10.1093/ecco-jcc/jjv219
PubMed ID:
26619893
Additional Links:
http://ecco-jcc.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=26619893
Type:
Journal Article
Language:
en
ISSN:
1876-4479
Appears in Collections:
2015 RD&E publications; Exeter Kidney Unit (Renal); Gastroenterology; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHeap, Graham Aen
dc.contributor.authorSo, Ken
dc.contributor.authorWeedon, Men
dc.contributor.authorEdney, Naomien
dc.contributor.authorBewshea, Claireen
dc.contributor.authorSingh, Abheyen
dc.contributor.authorAnnese, Ven
dc.contributor.authorBeckly, Jen
dc.contributor.authorBuurman, Den
dc.contributor.authorChaudhary, Ren
dc.contributor.authorCole, A Ten
dc.contributor.authorCooper, S Cen
dc.contributor.authorCreed, Ten
dc.contributor.authorCummings, Fen
dc.contributor.authorde Boer, N Ken
dc.contributor.authorD'Inca, Ren
dc.contributor.authorD'Souza, Richarden
dc.contributor.authorDaneshmend, T Ken
dc.contributor.authorDelaney, Men
dc.contributor.authorDhar, Aen
dc.contributor.authorDirekze, Nen
dc.contributor.authorDunckley, Pen
dc.contributor.authorGaya, D Ren
dc.contributor.authorGearry, Ren
dc.contributor.authorGore, Sen
dc.contributor.authorHalfvarsson, Jen
dc.contributor.authorHart, Aen
dc.contributor.authorHawkey, C Jen
dc.contributor.authorHoentjen, Fen
dc.contributor.authorIqbal, Ten
dc.contributor.authorIrving, Pen
dc.contributor.authorLal, Sen
dc.contributor.authorLawrance, Ien
dc.contributor.authorLees, C Wen
dc.contributor.authorLewis, Sen
dc.contributor.authorLockett, Men
dc.contributor.authorMann, Sen
dc.contributor.authorMansfield, Jen
dc.contributor.authorMowat, Cen
dc.contributor.authorMulgrew, Chris Jen
dc.contributor.authorMuller, Fen
dc.contributor.authorMurray, Cen
dc.contributor.authorOram, Richarden
dc.contributor.authorOrchard, Ten
dc.contributor.authorParkes, Men
dc.contributor.authorPhillips, Ren
dc.contributor.authorPollok, Ren
dc.contributor.authorRadford-Smith, Gen
dc.contributor.authorSebastian, Sen
dc.contributor.authorSen, Sen
dc.contributor.authorShirazi, Ten
dc.contributor.authorSilverberg, Men
dc.contributor.authorSolomon, Len
dc.contributor.authorSturniolo, G Cen
dc.contributor.authorThomas, Men
dc.contributor.authorTremelling, Men
dc.contributor.authorTsianos, E Ven
dc.contributor.authorWatts, Den
dc.contributor.authorWeaver, Sen
dc.contributor.authorWeersma, R Ken
dc.contributor.authorWesley, Een
dc.contributor.authorHolden, Aren
dc.contributor.authorAhmad, Tariqen
dc.date.accessioned2015-12-23T13:46:09Zen
dc.date.available2015-12-23T13:46:09Zen
dc.date.issued2015-11-29en
dc.identifier.citationClinical features and HLA association of 5-Aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease. 2016 Feb;10(2):149-58en
dc.identifier.issn1876-4479en
dc.identifier.pmid26619893en
dc.identifier.doi10.1093/ecco-jcc/jjv219en
dc.identifier.urihttp://hdl.handle.net/11287/592562en
dc.description.abstractBackground & 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.en
dc.languageENGen
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urlhttp://ecco-jcc.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=26619893en
dc.rightsArchived with thanks to Journal of Crohn's & colitisen
dc.titleClinical features and HLA association of 5-Aminosalicylate (5-ASA) induced nephrotoxicity in inflammatory bowel disease.en
dc.typeJournal Articleen
dc.identifier.journalJournal of Crohn's & Colitisen
dc.type.versionIn press (epub ahead of print)en

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