Expression of renal cystic genes in patients with HNF1B mutations

HNF1B nephropathy is characterized by dominantly inherited renal hypodysplasia with few cysts, slow renal decline and hypomagnesemia. Mice with antenatal inactivation of HNF1B are characterized by polycystic kidneys, renal failure and a profound decrease in cystic gene (Pkhd1, Umod, Pkd2) expression. Mice with inactivation after postnatal day 10 have no renal phenotype.

Quantification of mRNA expression of HNF1B, six of its potential target genes (PKHD1, PKD1, PKD2, IFT88, TMEM27 and UMOD) and three genes involved in the Mg(2+) renal homeostasis (ATP1A1, FXYD2 and CLDN16) in the urinary sediment of 11 individuals with mutation of HNF1B and in 9 controls (non-invasive assessment of the renal transcriptome).

As compared to controls, no difference was observed in the urinary mRNA amount of HNF1B and the renal cystic genes. A significant increase in the expression of ATP1A1, which encodes the α1-subunit of the Na(+)/K(+)-ATPase, was identified in HNF1B patients consistent with its role in Mg(2+) homeostasis.

Assessment of mRNA expression in urinary sediment is a non-invasive method applicable to gain insights into the pathophysiology of inherited nephropathies in humans. HNF1B nephropathy is generally not associated with postnatal down-expression of renal cystic genes in human, a finding consistent with mouse models.