dc.contributor.author | Clissold, RL | |
dc.contributor.author | Fulford, J | |
dc.contributor.author | Hudson, M | |
dc.contributor.author | Shields, BM | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Bingham, C | |
dc.date.accessioned | 2018-08-20T15:02:35Z | |
dc.date.issued | 2018-01-30 | |
dc.description.abstract | Background: Heterozygous mutations in the HNF1B gene are the most common monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently occur, including diabetes mellitus and pancreatic hypoplasia; the latter is associated with subclinical exocrine dysfunction. We measured faecal elastase-1 in patients with HNF1B-associated disease regardless of diabetes status and assessed the degree of symptoms associated with pancreatic exocrine deficiency. Methods: Faecal elastase-1 was measured in 29 patients with a known HNF1B mutation. We defined a low faecal elastase-1 concentration based on the 2.5 percentile of 99 healthy control individuals (410 μg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n = 6) underwent pancreatic imaging. Results: Faecal elastase-1 was below the 2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. A total of 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at <200 μg/g stool; of these, 3 suffered with abdominal pain, loose stools and/or unintentional weight loss. All three experienced symptomatic improvement and weight gain after commencing pancreatic enzyme replacement therapy. Faecal elastase-1 was low in 7/15 (47%) HNF1B patients without diabetes compared with 11/14 (79%) of those with diabetes (P = 0.1). Conclusions: Faecal elastase-1 deficiency is a common feature of HNF1B-associated renal disease even when diabetes is not present and pancreatic exocrine deficiency may be more symptomatic than previously suggested. Faecal elastase-1 should be measured in all patients with known HNF1B-associated disease complaining of chronic abdominal pain, loose stools or unintentional weight loss. The discovery of a low faecal elastase-1 concentration in individuals with developmental kidney disease of uncertain cause should prompt referral for HNF1B genetic testing. | en_GB |
dc.description.sponsorship | R.C. is supported by a Medical Research Council Clinical
Training Fellowship (grant reference number MR/J011630/1).
B.S. and A.H. are core members of the National Institute for
Health Research Exeter Clinical Research Facility. A.H. is a
National Institute for Health Research Senior Investigator.
S.E. and A.H. are supported by a Wellcome Trust Senior
Investigator award | en_GB |
dc.identifier.citation | Vol. 11 (4), pp. 453 - 458 | en_GB |
dc.identifier.doi | 10.1093/ckj/sfx150 | |
dc.identifier.uri | http://hdl.handle.net/10871/33795 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press | en_GB |
dc.relation.source | Supplementary data are available at ckj online. | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/30094008 | en_GB |
dc.relation.url | http://hdl.handle.net/10871/31005 | |
dc.rights | © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | HNF1B | en_GB |
dc.subject | developmental kidney disease | en_GB |
dc.subject | diabetes mellitus | en_GB |
dc.subject | faecal elastase | en_GB |
dc.subject | pancreatic hypoplasia | en_GB |
dc.title | Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-08-20T15:02:35Z | |
dc.identifier.issn | 2048-8505 | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available on open access from the publisher via the DOI in this record. | en_GB |
dc.description | The author accepted manuscript version of this article is in ORE at http://hdl.handle.net/10871/31005 | |
dc.identifier.journal | Clinical Kidney Journal | en_GB |