Background and aims Hepatocyte nuclear factor 1 beta (HNF1B) is involved in the development of kidneys, liver, pancreas and urogenital tract. Disorders have an extremely high heterogeneity in phenotype. We aim to define accurate criteria for screening in a prospective cohort of patients.
Methods Based on the phenotypic characteristics described in literature, we defined major, minor and extra-renal selection criteria. Major criteria were defined as fetal bilateral hyperechogenic kidneys; multicystic dysplastic kidney or renal agenesis; hypoplastic or dysplastic kidneys or cysts from unknown origin. Minor criteria were defined as ectopic kidney; vesico-ureteral reflux; hydronephrosis and extrarenal criteria as diabetes; hypomagnesemia; hyperuricemia; hypokalemia; liver function abnormalities or positive familial history.
We included all patients from our paediatric and adult nephrology department from January 2010 till April 2013 presenting with at least one major or one minor criterion with extra-renal manifestations in the personal or familial history.
Results We screened a prospective cohort of 252 patients fitting the criteria mentioned above and detected HNF1B mutations in 10% (n = 20), with a complete deletion being the most common (n = 10), besides duplication or sequence abnormalities. In our cohort the best predictors for finding HNF1B mutations were bilateral renal abnormalities (p < . 001) and cysts from unknown origin (p = . 03).
Conclusions Based on a prospective single centre cohort, we demonstrated that HNF1B-mutations are responsible for approximately 10% of CAKUT cases. Nonetheless, bilateral renal anomalies or cysts from unknown origin were the best predictors. These criteria might be useful for a more restricted screening protocol, but should be reaffirmed in a larger multicenter cohort.