Reduction of vitamin D induced stone formation by calcium.
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 Goe 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 proceses are important for 1,25-DHCC-induced nephrolithiasis.
Strohmaier
W L
WL
Department of Urology, Eberhard-Karls University, Tübingen, Germany.
Seeger
R D
RD
Osswald
H
H
Bichler
K H
KH
D000818:Animals; D002117:Calcitriol / Q000037:antagonists & inhibitors* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D007669:Kidney Calculi / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; C078495:Go 6070; D009287:Naphthyridines; D002117:Calcitriol; D002118:Calcium