Nephrocalcinosis in vitro

In order to study the mechanism of dystrophic calcification, an anoxic incubation of rat renal cortex in a tissue culture medium was performed in vitro. Calcium and phosphate in the medium were adjusted to 1.6 and 1.2 mM/1 respectively. Calcification occurred in apposition to the inner surface of membranous cellular degradation products and associated with the flocculent densities within the degenerate organelles. The chemical nature of the flocculent density was not determined. In view of the known affinity of calcium for acidic phospholipids, particularly phosphatidyl serine (PS), which lines the inner surface of the plasma membrane, calcification along the inner surface of membrane was thought to be related to the presence of PS. Accumulation of calcium in mitochondria, which is presumably dependent upon residual substrate for energy production, appeared to cause calcification as well. Amorphous calcium phosphate in the form of spheroids, and possibly fine fibrils and granules, also appeared to play a role in calcification by their transformation into apatite. The seemingly simple phenomenon of tissue calcification is complex. Nephrocalcinosis in vitro is remarkably similar to the calcification in acute tubular necrosis in vivo, and is a convenient model with which to study the mechanism of calcification. It is concluded that the cellular degradation products are the initial loci of calcification and have a likely role in urolithiasis.