4.1.7 Nephrocalcinosis

Definition: Calcium salt deposits (excluding calcium oxalate) in any renal compartment i.e. arteries, glomeruli and most often tubulointerstitial space.

Two types of nephrocacinosis must be distinguished: dystrophic calcification:

1. calcification of necrotic cells

2. metastatic calcification due to

2.1 hypercalciuria (with or without hypercalcemia) or

2.2 hyperphosphaturia.

Calcium deposits are very common and are said to be present in all patients in the medulla in autopsies. Cacium deposits may be overlooked in the PAS stain, they are blue in the HE stain and can be stained specifically with Kossa stain, which also stains phosphate.

In case of dystrophic calcification necrotic tubular cells are calcified, shed into the tubular lumens and may form casts. Casts obstruct the lumens and cause tubular dilatation in the proximal parts of the nephron.  The primary lesion is cell necrosis. The extend of renal damage depends on the extent of necrosis. In infarcts, calcification always starts in the periphery.

In case of metastatic calcification hypercalciuria is always present with or without hypercalcemia.

Metastatic calcification starts in the medulla. Calcium salt deposits, either calcium apatite or carbonate, are found in the tubular lumens, within tubular cells (only seen by electron microscopy), in the tubular basement membranes (mostly of the proximal tubules) and the adjacent interstitial space. We believe that the cacium deposits in the tubular lumen cause single cell necrosis of the nearby epithelium, pass through the BM and come to lay in the surrounding interstitial space.

The consequenes of nephrocacinosis are highly variable and depend on the extent of calcification. Papillary deposits (so called Randall plaques) have no effect on renal function. Minor deposits in the medulla pass unnoticed. However, extensive calcifications with obstruction of the tubular lumens, calcification of the tubular BM, eventually of interstitial collagen, more rarely glomeruli and arteries are accompanied by extensive interstitial fibrosis and tubular atrophy with little inflammation.

Cacium deposits in the tubular lumens have a variable appearance which are best differentiated using the HE stain. They may be finely granular, clumpy or shell / onion shape like. Granular and clumpy deposits are mainly found in hyercalciuria, shell like calcifications in patients with hyperphosphaturia. Differentiation of the morphological appearance may be helpful to distinguish different etiologies.