Medullary nephrocalcinosis (95% of all nephrocalcinoses) is usually associated with hypercalciuria and often with hypercalcemia. Approximately 40% of cases of medullary nephrocalcicosis are attributable to primary hyperparathyroidism, another 20% to renal tubular acidosis, and the remaining 40% divided among many other causes. Most of the conditions that cause nephrocalcinosis can also result in nephrolithiasis. Their coexistence helps establish the etiology and may significantly impact patient management. The appearance of medullary nephrocalcinosis equates to calcifications involving the distal convoluted tubules in the loops of Henle.

HYPERCALCIURIA, in general, is due to to dissolution of the bone, excessive ingestion or absorption of calcium from the gastrointestinal tract, or faulty renal reabsorption of calcium. Hyperparathyroidism is the most common single cause. Medullary nephrocalcicosis is seen in 5% of those with primary hyperparathyroidism (parathyroid adenoma), and nephrolithiasis is seen in 50-80% of these patients. Secondary hyperparathyroidism (usually due to renal disease) is a much less likely cause.

RENAL TUBULAR ACIDOSIS is characterized by abnormal renal tubular function that results in chronic systemic acidosis and a persistent alkali urine. There are two types of RTA. Type II RTA consists of proximal abnormalities, in which there is a greater than normal loss of bicarbonate, and renal calculi are not formed. Distal tubular dysfunction (type I RTA) interferes with hydrogen ion transfer into the urine, and may result in stone formation. 30% of infants and 70% of adults with type I RTA develop medullary nephrocalcicosis or nephrolithiasis. RTA may cause delayed skeletal maturation and osteomalacia. Primary RTA results from an inherited enzymatic defect. Diseases known to cause secondary RTA include Wilson’s disease, Fanconi’s syndrome, hyperglobinemias, nephrotoxic drugs (outdated tetracycline, amphotericine B), and acetazolamide administration. These processes (primary or secondary causes of RTA) result in an inability to acidify urine. Since calcium ions are much more soluble in acidic urine crystalline calcium salts precipitate.

RENAL TUBULAR ECTASIA, or medullary sponge kidney, is a disease in which the terminal nephrons and ducts of Bellini are dilated. Calculi form in about half the cases owing to stasis of urine in these dilated ducts. Approximately 15% of these patients develop calcifications, which may be present in both kidneys, one kidney, or even a single collecting system.

Medullary nephrocalcicosis and urolithiasis occur in a variety of other conditions, including but not limited to sarcoidosis, Cushing syndrome diabetes insipidus, hyperthyroidism, milk-alkali syndrome (excess calcium + alkali = milk + antacids), and hypervitaminosis D.