Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Abstract

Hepatocyte nuclear factor 1b (HNF1b)-associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1b transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1b-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1b-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1b-associated disease for the nephrologist.

A Rare Cause of Polyuria and Polydipsia in a Patient With Cystic Renal Disease: Maturity-Onset Diabetes of the Young Type 5

“…In this context, renal involvement seems to be the first manifestation of MODY 5 and some of these features can be identified by antenatal ultrasound [5,6,13]. The most frequent antenatal presentation is bilateral hyperechogenic kidneys with normal or increased size [6,14].…”

“…Decramer et al [14] screened on the diagnosis of fetal bilateral hyperechogenic kidneys and found HNF-1β mutations in 29% of the 56 newborn infants. HNF-1β appears to be a main regulator in the expression of genes of which mutations are responsible for cystic kidney diseases (Nphp1, polaris, Umod, Pkhd1, and Pkd2) [5]. The finding of polycystic kidneys is not unpredicted in patients with TCF2 mutation.…”

“…In cases of moderately enlarged hyperechoic kidneys (+2 SD for age) during the second and third trimester, diagnoses of autosomal recessive polycystic kidney disease (ARPKD), autosomal-dominant polycystic kidney disease (ADPKD) and transcription factor 2 (TCF-2) gene mutation related nephropathy should be considered [2,3]. TCF-2 mutations may be involved in a wide spectrum of renal phenotypes that include renal cysts/ renal hyperechogenicity, renal hypoplasia/cystic dysplasia, dysmorphic calyces, urinary tract dilatation, vesico-ureteric reflux, horseshoe kidney and renal agenesis [4][5][6][7].…”

“…Hepatocyte nuclear factor-1beta (HNF-1β) encoded by the TCF2 gene is involved in the embryonic development of liver, kidney, intestine and pancreatic islets and plays a role in the specific regulation of gene expression of these organs [4,5]. Also, HNF-1β-regulated genes cause extra-renal abnormalities such as genital malformations (uterus agenesis, bicornuate uterus, agenesis of deferens channels, and hypospadias), abnormal liver function, hypomagnesaemia, hyperuricaemia and early-onset gout [4][5][6].…”

“…Also, HNF-1β-regulated genes cause extra-renal abnormalities such as genital malformations (uterus agenesis, bicornuate uterus, agenesis of deferens channels, and hypospadias), abnormal liver function, hypomagnesaemia, hyperuricaemia and early-onset gout [4][5][6].…”