Distinct phenotype of kidney stone formers with renal phosphate leak

Hypercalciuria is the most frequent metabolic disorder encountered in kidney stone formers (SF). Reduced renal phosphate reabsorption (i.e. renal phosphate leak) was proposed to be a driver of hypercalciuria in calcium SF. However, the phenotype of SF with renal phosphate leak remains poorly defined and the association of renal phosphate leak with stone history, stone composition and bone mineral density (BMD) has not been studied.

To fill these knowledge gaps, we conducted a cross-sectional analysis in a cohort of 555 idiopathic calcareous SF. The ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR) was used to evaluate renal phosphate transport.

Multivariable regression analyses revealed a negative association of parathyroid hormone (PTH), a positive association of 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) but no association of fibroblast growth factor 23 (FGF23) with TmP/GFR. SF with low TmP/GFR had their first stone event at a younger age and were more likely to have a positive family history of kidney stones. In addition, urinary calcium excretion and prevalence of brushite stones were significantly higher in SF with low TmP/GFR. However, BMD, measured by dual-energy X-ray absorptiometry, was not associated with TmP/GFR in SF.

Renal phosphate handling has a strong heritable component in SF and correlates with PTH, 25(OH)D and 1,25(OH)2D, but not with FGF23 levels. Furthermore, a low TmP/GFR (i.e. a renal phosphate leak) is associated with higher urinary calcium excretion and an increased prevalence of brushite stones.