Mitochondrial granulation in the proximal renal tubule in uremia

Mitochondria contain electron-dense particles, partly composed of an amorphous form of calcium phosphate. We have used electron microscopy from percutaneous renal biopsy material to analyze mitochondrial granulation in the proximal renal tubule of nonuremic and uremic children. Based on a technique of cutting mitochondria from ten electron micrographs per biopsy, counting the granules in each mitochondrion and weighing the paper, we found that mitochondria of nonuremic children averaged 23.7 +/- 1.2 granules/g paper while uremic children had only 11.8 +/- 1.1 granules/g. The number of granules per gram was unrelated to the serum calcium phosphate solubility product. A significant decrease in calcium granulation in uremia can also be produced experimentally in rats. Control rats averaged 14.7 +/- 1.5 granules/g, while rats made uremic by partial nephrectomy had 6.0 +/- 0.7 granules/g. Treatment of uremic rats with a pharmacological dose of vitamin D restored granulation to normal within 24 h. The significant decrease in calcium phosphate granulation in the renal proximal tubule in uremic children and in experimental animals is probably related to the documented loss of 1 alpha-hydroxylation of vitamin D in uremia.