Hypercalciuria and nephrocalcinosis

Mis-localisation of annexin 2 has recently been implicated in the pathogenesis of Dent s disease. This term is now used collectively to describe what was previously four conditions that affect kidney function X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphatemic rickets, idiopathic low molecular weight proteinuria with hypercalciuria and nephrocalcinosis and Dent s disease. Patients with this condition present with low molecular weight proteinuria and hypercalciuria. Renal stones, nephrocalcinosis and renal failure are common late-stage developments. The condition has been attributed to abnormal acidification within endosomes of the proximal tubular cells. It is very rare and is usually caused by mutations in the voltage-dependent Cl /H+ chloride antiporter CLCN5, but occasionally in the PI4,5P2 5-phosphatase, OCRL1 (oculocerebrorenal syndrome of Lowe protein 1). 

Hypercalciuria and nephrocalcinosis, a feature of Wilson s disease. Nephron 1993 65 460-462... 

Muller D, Eggert P, Krawinkel M. Hypercalciuria and nephrocalcinosis in a patient receiving long-term parenteral nutrition the effect of intravenous chlorothiazide. J Pediatr Gastroenterol Nutr 1998 27(1) 106-10. 

Hypercalciuria and nephrocalcinosis are the presenting signs in patients with Wilson disease. Hypercalciuria is possibly the consequence of a tubular defect in calcium reabsorption. Penicillamine therapy was accompanied by a decrease in urinary calcium excretion to normal values in half of the patients studied. 

Four children with the nephrotic syndrome developed transient hypercalciuria and intraluminal calcification in renal histopathological specimens without radiological evidence of renal calcification. These children were resistant to corticosteroids and were receiving furosemide plus albumin for the management of edema (10). This result stresses the pervasive effect of furosemide, and probably all loop diuretics, in increasing urinary calcium excretion, with resultant nephrocalcinosis. Whenever possible, steps should be taken to limit the hypercalciuric effect of loop diuretics. Such maneuvers could include limiting the sodium content of the diet and/or combining the loop diuretic with a thiazide diuretic. 

After persistent hypercalciuria, osteopenia can develop, causing metabolic bone disease, pathological fractures, and immobilization. Hypercalciuria can also lead to nephrolithiasis and nephrocalcinosis, factors that can impair renal function. Intravenous chlorothiazide has been successfully used for its hypocalciuric effect, with remarkable effect over a period of 6 months in a 13-year-old child who had received parenteral nutrition for 6 years. Calcium excretion and tubular reabsorption of phosphate returned to normal (48). What is not clear from this study is whether the drug actually has a positive long-term beneficial effect on metabolic bone disease. 

Misselwitz J, Hesse V, Markestad T. Nephrocalcinosis, hypercalciuria and elevated serum levels of 1,25-dihydroxy-vitamin D in children. Possible link to vitamin D toxicity. Acta Paediatr Scand 1990 79(6-7) 637-43. 

Diuretics have been shown to have variable effects in relationship to urinary calcium excretion and supersaturation, most notably including loop diuretic induced hypercalciuria and attenuation of urinary calcium excretion by thiazide diuretics. The factors contributing to nephrotoxicity are most commonly associated with multiple factors that favor calcium salt or uric acid deposition at the tubulo-interstitial level. Management of renal stone formation and nephrocalcinosis therefore presents a unique clinical challenge, balancing factors that increase risk for abnormal calcium salt deposition or crystallization, and factors that reduce this risk. 

Deficient P450c24 activity is a recently described cause of neonatal hypercalcemia, with hypercalciuria or nephrocalcinosis, normal 250HD levels, normal to moderately elevated 1,25(0H)2D levels, and low PTH [205], Another infant had failure to thrive, hypercalcemia, hypercalciuria, bilateral nephrocalcinosis, suppressed... 

Sodium cellulose phosphate is used in the treatment of adsorptive hypercalciura and nephrocalcinosis (both a common cause of kidney stones). The ability of inorganic esters of cellulose to function as ion exchangers, described previously, is the key to the use of sodium cellulose phosphate in the treatment of adsorptive hypercalciuria. Hypercalciuria is an increased level of calcium in a patient s urine. This disorder commonly results in painful kidney stones. Sodium cellulose phosphate has been used to complex the calcium ions and thus remove them from the patient and minimize the risk of stone formation (50-54). 

Fig.20.12a,b. An 11-year-old boy with medullary sponge kidney and hypercalciuria. a Sonogram of right kidney showing dilated collecting ducts and nephrocalcinosis. b Abdominal X-ray showing renal stones on both sides... 

Mocan H, Yildiran A, Camhbel T, Kuzey GM. Microscopic nephrocalcinosis and hypercalciuria in nephrotic syndrome. Hum Pathol 2000 31(ll) 1363-7. 

In an attempt to compensate for the acidosis, bone salts are mobilized. Unless the patient is treated with alkalies, bone salt mobilization results in osteomalacia. Calcium is excreted in the urine, and the combination of high calcium levels, high pH, and low citrate concentration in the tubular fluid facilitates precipitation of calcium salts, thus leading to nephrocalcinosis. Secondary hyperparathyroidism develops as a consequence of the negative calcium balance. The inability to concentrate urine and the accompanying polyuria result in part from the hypokalemia and in part from the hypercalciuria. 

The most important task in children with nephrocalcinosis is to identify the presence or absence of hypercalcemia and hypercalciuria. After that, hyperoxaluria and hypocitraturia should be screened for. 

Nephrolithiasis and/or nephrocalcinosis may be additional findings on sonography and can be confirmed on plain abdominal radiograph. Renal or urinary tract stones are found in uropathies caused by recurrent urinary infections and urine stasis. Nephrocalcinosis may be the consequence of acid-base disturbance and hypercalciuria in congenital tubulopathies. The presence of nephrocalcinosis and nephrolithiasis favors primary hyperoxaluria type 1 (PH 1) as diagnosis. This autosomal recessive inherited disease is caused by a deficiency of the liver-specific peroxisomal enzyme alanine-gly-... 

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