Reduction of vitamin D induced stone formation by calcium

Abstract

Investigations were carried out as to whether cytoprotective agents such as calcium antagonists can influence vitamin D induced nephrolithiasis. Increased vitamin D levels are found in 10–30% of all calcium oxalate stone formers. Male rats were assigned to one of the following groups: (1) 1,25-dihydroxycholecalciferol (DHCC) (n=8), (2) 1,25-DHCC+calcium antagonist Goe 6070 (a new 1,4-dihydronaphthyridine, Goedecke, Berlin) (n=8), or (3) control (n=8). 1,25-DHCC was administered for 6 days (120 pmol/24 h s.c.), Goe 6070 (1 mg/kg/24 h) by gavage. Clearance studies were performed on day 6. Kidneys were taken for histological examination and determination of calcium tissue content. 1,25-DHCC induced substantial concrement formation, which could be significantly limited by Geo 6070. The calcium tissue content was also reduced (0.17 vs. 0.04 mg/100 mg dry weight). 1,25-DHCC induced a dramatic fall in the glomerular filtration rate (GFR) (3.84 ml/min per kilogram). This reduction could be almost completely inhibited by the concomitant application of Goe 6070 (9.4 ml/min per kilogram; control 10.7 ml/min per kilogram). Goe 6070 did not influence the calcium handling. The results demonstrate a protective effect of Goe 6070 on vitamin D induced nephrolithias. The histological pattern (intracellular and membrane-bound concretions) and the fact that biochemical parameters were not influenced significantly by Goe 6070 indicate that cellular processes are important for 1,25-DHCC-induced nephrolithiasis.