Clinical Investigation

Kidney International (1985) 27, 774–779; doi:10.1038/ki.1985.79

Calcium metabolism in uremic nephrocalcinosis: Preventive effect of verapamil

Michael S Goligorsky1, Cidio Chaimovitz1, Jayson Rapoport1, Jed Goldstein1 and Rina Kol1

1Departments of Nephrology and Pathology, Soroka University Hospital and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Correspondence: Dr M S Goligorsky, Jewish Hospital of St. Louis, Renal Division, 216 South Kingshighway, St. Louis, Missouri 63110, USA

Received 20 April 1984; Revised 12 November 1984.

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Abstract

Calcium metabolism in uremic nephrocalcinosis: Preventive effect of verapamil. The aim of the present study was to examine calcium metabolism of the renal cortex in experimental chronic renal failure, together with morphologic criteria of nephrocalcinosis and to determine the effect of chronic verapamil administration on these parameters. In subtotally nephrectomized (SNX) rats 3 weeks after surgery, renal cortical calcium content increased more than two-fold, 45Ca incorporation into renal cortical slices in SNX revealed a 35% increase, associated with a 50% increase in a lanthanum-resistant fraction of 45Ca uptake. Radiocalcium wash-out curves in this group demonstrated abnormal retention of the isotope for up to 30 min of incubation, In contrast, radiocalcium incorporation and wash-out in SNX rats chronically treated with verapamil were similar to that obtained in the sham group. Verapamil administration significantly reduced, but did not normalize, renal cortical calcium content. Von Kossa staining demonstrated the deposition of calcium in the renal parenchyma of SNX rats. Ultrastructurally, it was accompanied by mitochondrial disorganization and calcification, as well as by the tubular basement membrane destruction and mineralization. These morphologic patterns of nephrocalcinosis were significantly ameliorated in SNX rats treated with verapamil. We conclude that chronic verapamil administration results in amelioration of uremic nephrocalcinosis.

Métabolisme du calcium au cours de la néphro-calcinose urémique: effet préventif du vérapamil. Le but de cette étude a été d'examiner le métabolisme calcique du cortex rénal au cours d'une insuffisance rénale chronique expérimentale en même temps que les critères morphologiques de néphrocalcinose, et de déterminer l'effet de l'administration chronique de vérapamil sur ces paramètres. Chez des rats néphrectomisés partiellement (SNX), 3 semaines après la chirurgie le contenu en calcium de la corticale rénale augmentait plus de deux fois. L'incorporation de 45Ca aux coupes de corticale rénale chez les SNX révélait une augmentation de 35%, associée à une élévation de 50% de la fraction lanthanum-résistante de la captation de 45Ca. Les courbes de disparition du radiocalcium dans ce groupe démontraient une rétention anormale de l'isotope jusqu'à 30 min d'incubation. A l'opposé, l'incorporation et la disparition du radiocalcium chez les rats SNX traités chroniquement au vérapamil étaient identiques à celles obtenues dans le groupe simulacre. L'administration de vérapamil a réduit significativement, mais n'a pas normalisé le contenu cortical rénal en calcium. Une coloration de Von Kossa a démontré des dépôts de calcium dans le parenchyme rénal des rats SNX. Ultrastructurallement, cela a été accompagné d'une désorganisation et de calcifications mitochondriales, et par une destruction et une minéralisation de la membrane basale tubulaire. Ces aspects morphologiques de néphrocalcinose étaient significativement améliorés chez les rats SNX traités au vérapamil. Nous concluons que l'administration chronique de vérapamil améliore la néphrolcalcinose urémique.

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