Project Details
Projekt
Formation mechanisms of calcium phosphate plaques and attached calcium oxalate kidney stones
Applicant
Professor Dr. Hans-Joachim Kleebe
Subject Area
Mineralogy, Petrology and Geochemistry
Reproductive Medicine, Urology
Reproductive Medicine, Urology
Term
from 2019 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 415094771
Calcium oxalate (CaOx) kidney stones are a major health problem, the causes and pathogenesis of which are not entirely clear, but are often related to metabolic disorders. After successful stone treatment, there is a high risk of recurrent CaOx stones. For most CaOx stones, a precondition appears to be the formation of calcium phosphate (CaP) precipitates in extracellular tissue of the kidney. These calcifications called Randall’s plaque (RP) form presumably during urine production in the tubular system of the kidney, when ions become reabsorbed and diffuse into the surrounding tissue. A local increase in pH and the concentrations of calcium and phosphate ions induce an increasing CaP supersaturation of the body fluid in the tissue. Inside the porous tissue various CaP minerals can form which may lead to lesions in the epithelium of the renal pelvis, where they come in contact with urine. Subsequently, CaOx stones form from urine by crystal growth at these RP surfaces. Certain naturally produced proteins, such as osteopontin (OPN), appear to inhibit the precipitation of CaP and CaOx in body fluid and in urine.However, the conditions of RP formation are not well known and the role of RP in the formation of CaOx stones is not entirely clear. Therefore, CaOx kidney stones and especially adherent RP will be investigated for their microstructures and local chemical and mineralogical composition with the aim of drawing conclusions about mechanisms of their formation. An attempt will be made to correlate characteristic signatures to specific metabolic disorders. In complementary model experiments based on ion diffusion in collagen, gelatin and agarose hydrogels, the formation of CaP plaques will be simulated. Additionally, the effect of OPN on CaP precipitation in these systems will be studied. Throughout the experiments, the formation of plaques will be monitored in situ using confocal Raman spectroscopy. Furthermore, samples will be characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffractometry, atomic force microscopy, atomic absorption spectroscopy and ion chromatography. Structural approximation of experimental CaP plaques to pathological RP is proposed to be achieved by iterative adjustment of the precipitation conditions in order to obtain clues about the conditions of RP formation. Finally, the proposed hypothesis, according to which calcium ions diffuse through RP and induce CaOx precipitation at the RP/urine interface, will be tested experimentally. These CaOx precipitates may serve as nuclei for the growth of larger stones from urine. Such an initiating mechanism would be particularly relevant for the formation of kidney stones and would promote their recurrence as well. It is expected that the results of this project enhance the understanding of the formation of RP and CaOx kidney stones and support the development of preventive medical treatments.
DFG Programme
Research Grants
