Nephrocalcinosis furosemide

Although it is often described in children, medullary nephrocalcinosis with furosemide has been rarely described in adults. 

A 40-year-old woman who had taken furosemide (40-160 mg/day) for 15 years developed medullary nephrocalcinosis (8). 

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. 

Simoes A, Domingos F, Praia MM. Nephrocalcinosis induced by furosemide in an adult patient with incomplete renal tubular acidosis. Nephrol Dial Transplant 2001 16(5) 1073. ... 

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]. 

SaarelaT, fanning P, Koivisto M, PaavilainenT. Nephrocalcinosis in full-term Infants receiving furosemide treatment for congestive heart failure a study of the Incidence and 2-year follow up. Eur J Pediatr 1999 158 668-672. 

Potential complications of long-term furosemide (frusemide) treatment in humans, in addition to the more obvious problems such as volume depletion and the development of azotemia, are potassium depletion leading to hypokalemia (see p. 353), nephrolithiasis, nephrocalcinosis and... 

Alon US, Scagliotti D, Garola RE. Nephrocalcinosis and nephrolithiasis in infants with congestive heart failure treated with furosemide. J Pediatr 1994 125 149-151. 

Urinary tract Administration of furosemide to preterm infants may increase the risk of nephrocalcinosis. In 55 neonates bom before 32 weeks of gestation a multivariate analysis showed that the strongest independent susceptibility factor for nephrocalcinosis was furosemide therapy in a cumulative dose of over lOmg/kg (OR=48 95% Cl = 4, 585) [13 ]. The risk of nephrocalcinosis increased in proportion to the urinary calcium concentration (OR=4.5 for each 1 mmol/1 increase 95% Cl = 1.1,18). 

Gimpel C, Krause A, Franck P, Krueger M, von Schnakenburg C. Exposure to furosemide as the strongest risk factor for nephrocalcinosis in preterm infants. Pediatr Int 2010 52(1) 51-6. 

Alon US (1997) Nephrocalcinosis. Pediatrics 9 160-165 Alon US, Scagliotti D, Garola RE (1994) Nephrocalcinosis and nephrolithiasis in infants with congestive heart failure treated with furosemide. J Pediatr 125 149-151 Arikyants N, Sarkissian A, Hesse A et al (2007) Xanthinuria type I-a rare cause of urolithiasis. Pediatr Nephrol 22 310-314... 

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