Disparate Effects of Vitamin D Treatment upon Mitochondrial Granulation in Proximal and Distal Renal Tubule

Abstract

The distribution of calcium phosphate granules in mitochondria of proximal and distal renal tubules of nonuremic and uremic children was analyzed by electron microscopy of material obtained by percutaneous kidney biopsy. Although distal tubule had fewer granules/mitochondrion than proximal tubule, uremia induced a significant drop (50%) in both, related to an increase in mitochondria containing O granules and a decrease in mitochondria with 2+ granules. The decrease observed in uremic children was reproduced experimentally by partial nephrectomy in rats. Uremia resulted in a 58% decrease of calcium phosphate granules in rat proximal tubule while a smaller but significant decrease (36%) occurred in distal tubule. Vitamin D deficiency in rats was associated with greatly decreased granulation in proximal tubule (80%) whereas distal tubule was less severely affected (36%). Supplementation of vitamin D to uremic rats restored mitochondrial granulation to normal in proximal tubule in 24 hr, but had no effect in distal tubule since the number of granules/mitochondrion, 0.5 +/- 0.1, remained statistically similar to that of untreated animals. Granulation in both proximal and distal tubule of uremic rats was unaffected by parathyroid hormone administration. Since restoration of granulation occurred only in proximal tubule, the defect in uremia which can be overcome by vitamin D treatment appears localized at the level of the proximal tubular cell membrane, indicating an action of vitamin D on calcium and/or phosphorus translocation into the proximal tubule.