Keywords [eng] |
HNF1B nefropatija, HNF1B asocijuota liga, pediatrija, ekstrarenalinės manifestacijos, ilgalaikės inkstų išeitys. HNF1B nephropathy, HNF1B-associated disease, pediatrics, extrarenal manifestations, long-term kidney outcomes. |
Abstract [eng] |
Adult manifestations of HNF1B deficiency are increasingly recognized, yet a comprehensive assessment of the phenotype and long-term kidney outcomes in HNF1B nephropathy across childhood and adulthood remains elusive. This systematic literature review aims to delineate the longitudinal trajectory of kidney function, kidney – associated complications, and extrarenal manifestations in genetically confirmed HNF1B nephropathy cases across pediatric and adult populations, offering practical recommendations for clinicians. Scientific publications were screened in PubMed/Medline database, resulting in 91 included studies with 528 eligible patients. Only full-text clinical case reports and case series with sufficient patient-level data were included for aggregated analysis. Of the patients, 52% presented with de novo HNF1B mutations and 48% with inherited mutations, with whole HNF1B gene deletion being the most prevalent mutation category up to age 50. Furthermore, a tendency for kidney function deterioration was observed, with an average yearly estimated glomerular filtration rate decline of -2.56 ml/min/1.73m². Linear regression analysis identified older age and higher estimated glomerular filtration rate at diagnosis as statistically significant predictors of estimated glomerular filtration rate change. Kaplan-Meier survival curve modeling revealed that by age 29, 10% of patients had reached chronic kidney disease stage 5, increasing to 40% by age 58, indicating a higher risk of progression to end-stage kidney disease. Prenatally, hyperechogenic kidneys were most prevalent (62%), while kidney cysts were more frequent at diagnosis (68%) and last follow-up (73%). Notably, proteinuria incidence (39%) exceeded hypertension (16%), and hyperuricemia emerged as the most prevalent extrarenal manifestation (41%), followed by diabetes (39%) and hypomagnesemia (32%). Proteinuria and hypomagnesemia were most common in the partial HNF1B gene deletion group (P = 0.008 and P = 0.006, respectively), while hyperuricemia predominated in the splice site mutation group (P = 0.002). 163 patients had diabetes, with a median onset age of 22 years (interquartile range: 19.5 years), spanning from 1 to 65 years, and occurring in 50% of cases by age 22. Clinicians should suspect HNF1B-associated disease in patients presenting with hyperechogenic kidneys and kidney cysts, particularly in those with concurrent diabetes, hyperuricemia or hypomagnesemia, even without a positive family history. These findings underscore the importance of regular kidney function monitoring and consideration of mutation type in patient management. |