Mineralisation in kidney disease
The tubular segments of the kidney play essential roles in the handling of specific solutes that either promote (e.g. Ca2+, Pi, oxalate) or inhibit (e.g. Mg2+, citrate, uromodulin) the formation of crystals in the lumen of the nephron, which may lead to kidney stones, kidney injury, inflammation, and eventually result in the evolution of chronic kidney disease (CKD). The main objective of this WP is to establish biochemical and/or genetic risk profiles and to identify potential targets to prevent or slow the development of CKD associated with crystallization disorders.
Uromodulin: from physiology to kidney disorders
This project focus on the following scientific questions:
- What are the physiological regulators of uromodulin production and what are the roles of the uromodulin matrix inside the lumen of kidney tubules?
- By which mechanisms UMOD mutations cause tubulointerstitial kidney disease and what is the role of ER/oxidative stress, unfolded protein response (UPR) and autophagy in the progression of CKD?
- What is the role of UMOD promoter variants and uromodulin in complex disorders including CKD and kidney stones?
- Devuyst O, Pattaro C. The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease. J Am Soc Nephrol. 29: 713-26 (2018)
- Devuyst O, Olinger E, Rampoldi L. Uromodulin: from physiology to rare and complex kidney disorders. Nat Rev Nephrol. 13: 525-44 (2017)
Phosphate transporters in renal disease
Renal phosphate (Pi) transport is mediated by several Pi transporters that when mutated in humans cause hypophosphatemia, hypercalciuria and kidney stones. Genetic variants in the two main Pi transporters, SLC34A1 and SLC34A3, are common. We examine the clinical and functional relevance of these variants for kidney stone disease and chronic kidney disease.
- Wagner CA, Rubio-Aliaga I, Hernando N. Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. Pediatr Nephrol. 34: 549-59 (2019)
- Thomas L, Bettoni C, Knöpfel T, Hernando N, Biber J, Wagner CA. Acute Adaption to Oral or Intravenous Phosphate Requires Parathyroid Hormone. J Am Soc Nephrol. 28: 903-14 (2017)
Magnesium & CKD
In this project a well characterized kidney transplant cohort is studied for a longitudinal analysis of the prevalence, determinants and impact of hypomagnesaemia on surrogate markers and hard endpoints of CKD and chronic venous disease (CVD) progression. The human studies are complemented by mechanistic studies in a mouse model of accelerated calcification and with development of end stage renal disease.