Hypercalcemia and Nephrocalcinosis

Disorders characterized by hypercalcemia, such as hyperparathyroidism, multiple myeloma, vitamin D intoxication, metastatic bone disease, or excess calcium intake (milk-alkali

syndrome), may induce the formation of calcium stones and deposition of calcium in the kidney (nephrocalcinosis). Extensive degrees of calcinosis, under certain conditions, may lead to a

form of chronic tubulointerstitial disease and renal insufficiency. The first damage induced by the hypercalcemia is at the intracellular level, in the tubular epithelial cells, resulting in

mitochondrial distortion and evidence of cell injury. Subsequently, calcium deposits can be demonstrated within the mitochondria, cytoplasm, and basement membrane. Calcified cellular

debris contributes to obstruction of tubular lumens and causes obstructive atrophy of nephrons with interstitial fibrosis and nonspecific chronic inflammation. Atrophy of entire cortical

areas drained by calcified tubules may occur, and this accounts for the alternating areas of normal and scarred parenchyma seen in such kidneys.

Figure 20-46Urate crystals in the renal medulla. Note the giant cells and fibrosis around the crystals.

TABLE 20-11-- Renal Involvement in Nonrenal Neoplasms

Direct tumor invasion of renal parenchyma

••Ureters (obstruction)

••Artery (renovascular hypertension)

Hypercalcemia

Hyperuricemia

Amyloidosis

Excretion of abnormal proteins (multiple myeloma)

Glomerulopathy

••Immune complex glomerulonephritis (carcinomas)

••Minimal change disease (Hodgkin disease)

••Membranoproliferative glomerulonephritis (leukemias and lymphomas)

Effects of radiotherapy, chemotherapy, secondary infection

Morphology.

The tubulointerstitial changes in multiple myeloma are fairly characteristic. The Bence Jones tubular casts appear as pink to blue amorphous masses, sometimes concentrically laminated,

often with a fractured appearance, filling and distending the tubular lumens. Some of the casts are surrounded by multinucleate giant cells that are derived from mononuclear phagocytes

( Fig. 20-47 ). The adjacent interstitial tissue usually shows a nonspecific inflammatory response and fibrosis. On occasion, the casts erode their way from the tubules into the interstitium

and here evoke a granulomatous inflammatory reaction. The histologic features of amyloidosis, light-chain deposition disease and nephrocalcinosis and infection, may also be present.

Clinically, the renal manifestations are of several types. In the most common form, chronic renal failure develops insidiously and usually progresses slowly during a period of several

months to years. Another form occurs suddenly and is manifested by acute renal failure with oliguria. Precipitating factors in these patients include dehydration, hypercalcemia, acute

infection, and treatment with nephrotoxic antibiotics. Bence Jones proteinuria occurs in 70% of patients with myeloma; the presence of significant non-light-chain proteinuria (e.g.,

albumin) suggests secondary amyloidosis or light-chain deposition disease.

Date: 2016-04-22; view: 837