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

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.

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 microg/g stool). Symptoms related to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort (n  =  6) underwent pancreatic imaging.

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 microg/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).

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.