Exocrine pancreatic dysfunction is common in HNF1B-associated renal disease and can be symptomatic
Clinical Kidney Journal
Oxford University Press (OUP)
VC 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.
Background Heterozygous mutations in the HNF1B gene are the commonest monogenic cause of developmental kidney disease. Extra-renal 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 2.5th percentile of 99 healthy control individuals (410 mcg/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 2.5th percentile of the control cohort in 18/29 (62%) patients with HNF1B-associated renal disease. 8/29 (28%) had a measurement suggestive of exocrine pancreatic insufficiency at <200 mcg/g stool; of these, three 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 to 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.
Rhian Clissold is supported by a Medical Research Council Clinical Training Fellowship (grant reference number MR/J011630/1). Beverley Shields and Andrew Hattersley are core members of the National Institute for Health Research Exeter Clinical Research Facility. Andrew Hattersley is a National Institute for Health Research Senior Investigator. Sian Ellard and Andrew Hattersley are supported by a Wellcome Trust Senior Investigator award.
This is the author accepted manuscript. The final version is available from OUP via the DOI in this record.
Published online 30-01-2018.