Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic

Abstract

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.