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Review
. 2016 Feb;27(2):345-53.
doi: 10.1681/ASN.2015050544. Epub 2015 Aug 28.

Hepatocyte Nuclear Factor 1β-Associated Kidney Disease: More than Renal Cysts and Diabetes

Jacobien C Verhave  1 , Anneke P Bech  1 , Jack F M Wetzels  1 , Tom Nijenhuis  2
Affiliations
Review

Hepatocyte Nuclear Factor 1β-Associated Kidney Disease: More than Renal Cysts and Diabetes

Jacobien C Verhave et al. J Am Soc Nephrol. 2016 Feb.

Abstract

Hepatocyte nuclear factor 1β (HNF1β)-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 HNF1β transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1β-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 HNF1β-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 HNF1β-associated disease for the nephrologist.

Keywords: CKD; clinical nephrology; cystic kidney; diabetes mellitus; electrolytes; genetic renal disease.

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Figures

Figure 1.
Figure 1.
Renal and extrarenal features of HNF1β-associated disease. The clinical signs and symptoms that are currently associated with HNF1B mutations and deletions are depicted.
Figure 2.
Figure 2.
HNF1β as a promiscuous transcription factor. Target genes known to be regulated by the HNF1β transcription factor in several organ systems, responsible for the diverse multisystem clinical signs and symptoms, are depicted.
See this image and copyright information in PMC

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