Studies of the genetic causes of idiopathic hypercalciuria

Project leader – Dr Sarah Howles, NIHR Clinical Lecturer

Kidney stones affect up to 20% of individuals during their lifetime. Unfortunately, most stone formers suffer recurrent episodes and current stone prevention strategies are relatively ineffective. Increased levels of urinary calcium are a major risk factor in kidney stone formation and half of all stone formers excrete high levels of urinary calcium without known underlying cause, a condition called idiopathic hypercalciuria. Twin studies of renal calcium excretion have demonstrated a genetic heritability of 52%; however, only four genetic loci of interest have been identified to date. An improved understanding of the causes of idiopathic hypercalciuria (IH) is of key importance in decreasing the incidence of renal stone disease.

Sarah’s project aims to investigate the genetic factors contributing to IH. By studying whole-genome sequencing data from families with idiopathic hypercalciuria and kidney stones, Sarah has identified a gene that may play a role in regulating renal calcium excretion via a previously unexplored pathway. Sarah will explore the role of the protein that this gene encodes in calcium transport and calcium homeostasis. Her aim is to increase understanding of how the kidney controls calcium excretion and to develop novel treatments for patients who suffer from recurrent kidney stone formation.

September 2017