Promotors: Patrick C. D'Haese, Anja Verhulst
As one of the primary functions of the kidney consists of filtering and concentrating ions in the renal tubules, tubular fluid is often supersaturated and crystal formation may occur. Hence, crystalluria (the urinary excretion of crystals) is frequently found in routine examination of urine sediments and is mostly harmless in the healthy population. Two salts that typically crystallize are calcium phosphate and calcium oxalate. Extensive calcium oxalate or calcium phosphate crystal formation is observed in the pathologies of oxalate nephropathy (primary and secondary hyperoxaluria) and acute phosphate nephropathy, respectively. The large amount of crystals formed in these pathologies result in crystal retention (nephrocalcinosis), which may progress towards renal insufficiency.
The aims of this research were:
- to develop and characterize physiologically and clinically relevant animal models for renal calcifications in the setting of primary and secondary hyperoxaluria and acute phosphate nephropathy;
- to study the effect of therapeutic interventions to prevent renal calcifications in these animal models;
- to gain more fundamental insight in the development and prevention of renal calcifications in these pathologies.
We found lanthanum carbonate to be a promising agent for future prevention/treatment of secondary hyperoxaluria. In a rat model of increased endogenous oxalate synthesis (primary hyperoxaluria), lanthanum carbonate was not able to reduce hyperoxaluria and renal CaOx calcifications. Finally, no evidence was found for an improved safety profile of oral sodium phosphate by inhibition of intestinal phosphate absorption in a new clinically relevant rat model of acute phosphate nephropathy.