Renal calcification

Calciferol may cause renal calcification by causing hypercalcaemia. 

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. 

Loop diuretic therapy has been implicated in the development of renal calcifications in both preterm and full-term infants [99-105]. In a study by Jacinto et al., nephrocalcinosis occurred in 20 of 31 (64%) of premature infants with birth weights less than 1500 g, with 65% of affected infants having received furo-semide [103]. Nephrocalcinosis was found in 14% of full-term infants with congestive heart failure receiving long-term furosemide therapy [104]- Furosemide may induce high urinary calcium excretion rates and low urinary citrate to creatinine ratio, risk factors for renal calcification [106]. 

Dose and length of therapy with loop diuretics may predict the likelihood of developing calcium deposits in the renal parenchyma. Ten premature infants developed nephrocalcinosis after receiving furosemide at a dose of at least 2 mg/kg per day for 12 days [102]. In a study by Saarela et al, infants who developed renal calcifications were receiving higher daily doses of furosemide than infants who had not developed this complication (1.9 + 0.6 vs. 1.3 + 0.4 mg/kg per day p value-0.01) [104]. Calcifications were diagnosed within a few months of initiating furosemide. 

Since unresolved nephrocalcinosis may lead to residual abnormalities in the kidney including microscopic hematuria, hypercalcemia, and impaired tubular function [100,104,105], renal ultrasonography within a few months of initiating loop diuretics may be warranted [100 104]. If long-term diuretic therapy is needed, a thiazide diuretic alone or in combination with furosemide may reduce the risk of renal calcifications by decreasing urinary calcium and oxalate excretion [100,102,104,107,108]. However, two studies of premature infants failed to show a reduction in either urinary oxalate or calcium excretion when thiazides were added to furosemide therapy [107,109]. 

Downing GJ, Egelhoff JC, Daily DK,Thomas MK, Alon U. Kidney function in very low birth weight infants with furosemide-related renal calcifications at ages 1 to 2 years. J Pediatr 1992 120 599-604. 

Flufnagle KG, Khan SN, Penn D, Cacciarelli A, Williams P. Renal calcifications a complication of long-term furosemide therapy in preterm infants. Pediatrics 1982 70 360-363. 

Jacinto JS, Modanlou FiD, Grade M, Strauss AA, Bosu SK. Renal calcification incidence in very low birth weight infants. Pediatrics 1988 81 31-35. 

Chau H, El-Maadawy S, McKee MD, Tenenhouse HS Renal calcification in mice homozygous for the disrupted type iia Na/Pi cotransporter gene Npt2. J Bone Miner Res. 2003 18 644-657. 

Oxalate as component and/or inducer of renal calcifications (nephrocalcinosis)... 

The high prevalence of oxalate containing renal (tubular) and urinary tract calcifications is related to the low solubility of the oxalate-calcium salt. High urine oxalate excretion increases urine calcium oxalate supersaturation and, therefore the risk of crystal formation in tubular fluid and urine. In human urine, calcium concentration is about ten fold higher than oxalate on molar base. Relatively modest increases in urine oxalate excretion will have significant effects on urine supersaturation [49], especially in patients with hypercalciuria where calcium is even in greater excess of oxalate. Nevertheless, most people do not suffer from renal calcifications [50-54], suggesting that renal protection mechanisms exist. 

Vitamin D Excess (vitamin D toxicosis) causes hypercalciuria and hypercalcemia, leading to urolithiasis and soft-tissue (especially renal) calcification insufficiency causes rickets and osteoporosis. As 1, 25-(0H)2D, increases bone resorption and intestinal and renal Ca " and phosphate absorption other metabolites may have other activities, especially in bone. 

Struthers et al. also reported that the Sprague-Dawley strain of rats was more susceptible to renal calcification. Woodard s group studied the Sprague-Dawley strain, deGroot s group studied the Wistar strain the difference in rat strains may explain the differences between Woodard s and deGroot s results. 

Giacomelli, F., Spiro, D., Wiener, J. A study of metastatic renal calcification at the cellular level. J. Cell Biol. 22, 189-206 (1964)... 

Jacinto JS, Modanlou HD, Grade MC, Strauss AA, Bosu SK (1988) Renal calcification incidence in very low hirth weight infants. Pediatrics 81 31-35 Jacohus CH, Holick MF, Shao Q, Chen TC, Holm lA, Kolodny JM, Fuleihan GE, Seely EW (1992) Hypervita-minosis D associated with drinking milk. N Engl J Med 326 1173-1177... 

Jdquier S, Kaplan BS (1991) Echogenic renal pyramids in children. J Clin Ultrasound 19 85-92 Kamitsuka MD, Peloquin D (1991) Renal calcification after dexamethasone in infants with hronchopulmonary dysplasia (letter). Lancet 337 626... 

Karlowicz MG, Adelman RD (1995) Renal calcification in the first year of life. Pediatr Clin North Am 42 1397-1413 Karlowicz MG, Adelman RD (1998) What are the possible causes of neonatal nephrocalcinosis Semin Nephrol (US) 18 364-367... 

Myracle MR, McGahan JP, Goetzman BW, Adelman RD (1986) Ultrasound diagnosis of renal calcification in infants on chronic furosemide therapy. J Clin Ultrasound 14 281-287... 

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