Introduction: Hepatocyte nuclear factor 1β (HNF1β) gene variants are the cause of an autosomal dominant syndromic disorder. At the moment of genetic confirmation of the diagnosis, the most frequent phenotypic expression of the HNF1β variant in the pediatric population is kidney disease (congenital anomaly of the kidney and urinary tract ± renal failure), and in adults diabetes mellitus (maturity-onset diabetes of the young 5-MODY5). Cases of phenotypic expression of diabetes mellitus after kidney transplantation in HNF1β variant carriers have been described, which can be linked to the use of prodiabetogenic immunosuppressive therapy. Our goal is to examine the frequency of phenotypic expression of insulin-dependent diabetes mellitus (MODY5) after kidney transplantation in children carrying the HNF1β gene variant.
Methods: We present the relevant clinical data of pediatric patients at the University Children's Hospital in Belgrade who were confirmed to have a pathogenic variant of the HNF1β gene in the period from July 2010 to January 2025.
Results: During this period HNF1β gene variants were confirmed in 10 patients. Genetic analysis of HNF1β gene revealed following variants: whole gene deletion (3), deletion of multiple exons (2), frameshift variants (2), nonsense (2) and missense variant (1 patient). The average follow-up period of our cohort was 13.4 (± 8.5) years. During this period, 7/10 (70 %) patients had progressive renal disease with an estimated glomerular filtration rate < 90 ml/min/1.73 m2, with 4/10 (40 %) requiring renal replacement therapy at a mean age of 13.5 (± 3.7) years. Kidney transplantation was performed in 3/4 (75%) patients with end-stage renal disease. All 3 (100%) transplanted patients developed insulin-dependent diabetes mellitus in the first month after kidney transplantation. At the moment of clinical manifestation of diabetes, all patients were treated with steroids and calcineurin inhibitors (in one patient tacrolimus and in two patients cyslosporine).
Conclusion: All transplanted patients developed diabetes in the early post-transplant period. A risk factor for the manifestation of diabetes mellitus, which is genetically predisposed in patients with the HNF1β variant, is kidney transplantation and use of prodiabetogenic immunosuppressive therapy. Immunosupressive regimens free of calcineurin inhibitors and corticosteroids should be considered in patients with HNF1β-associated disease.