Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis

Abstract

The administration of ceftriaxone is known to be associated with biliary pseudolithiasis, although the development of urolithiasis has only rarely been reported. We treated a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt, which prompted us to study whether ceftriaxone administration predisposes children to the formation of urinary precipitates. The case-control study reported here included 83 children with bacterial pneumonia aged from 3 months to 8.9 years. The children were divided into one group of 43 children who received ceftriaxone (group A) and a second group of 40 children who received amoxicillin (group B). Paired samples of serum and urine before and after treatment were obtained from the patients in each group. There were no significant differences in demographic characteristics and blood biochemistry between the groups. However, the mean urinary calcium to creatinine ratio (uCa/Cr; mg/mg) was significantly higher in group A patients than in group B patients after treatment (0.19 vs. 0.09, respectively; p < 0.001), and analysis of the paired urine samples revealed that the uCa/Cr significantly increased after treatment only in group A patients(p < 0.001). There was a weak but non-significant relationship between the dose of ceftriaxone and the uCa/Cr in group A (p = 0.10, r = 0.24). Our results are the first to demonstrate that ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. We therefore suggest that it is worthwhile monitoring the uCa/Cr levels in patients on ceftriaxone as they may be at greater risk for developing large stones and renal damage.

Urine saturation and promoter/inhibitor parameters and ratios in renal stone disease caused by ceftriaxone

“…is the first case report of urine glycosaminoglycans and urine saturation in patient with cephtriaxone urinary stones. We observed an increased level of calcium excretion during ceftriaxone treatment as compared with the same analysis performed 2 months later, which is in accordance with previous observations [9]. However, urinary calcium excretion was not in the range of hypercalciuria.…”

“…A possible prevention of such stone formation would be to maintain alkaline urinary pH during ceftriaxone therapy and look out for concomitant urinary tract infection with nanobacteria [18]. Our data is pointing out that a search for causes of ceftriaxone urolythiasis is less plausible in the urine following, rather than in the stone formation phase [9]. Although, we suppose that urineanalysis during acute stone formation phase will provide more consistant results.course, a single case report bears significant limitation to this conclusion.…”

“…As both ceftriaxone and carbonate phosphate [10,11] possess high calcium-binding affinity, such mixture has high potential for a stone formation, especially when the calcium urinary excretion is increased [10,16]. A recent study has proven a convincing association of increased calcium excretion with ceftriaxone treatment [9]. Such formed stones are fairly rarewide use of ceftriaxone, yet additional risk(s) factors for stone formation are still expected.…”

“…Some investigations point to possible association with increased urinary calcium excretion, although majority of reports declare unclear results. We describe a case of a boy with gallblader and urinary stones of ceftriaxone composition, ensued during subdural empyema antibacterial therapy [8][9][10].…”

Ceftriaxone and Acute Renal Failure in Children

“…5 It can even increase urinary calcium excretion. 12 Thus ceftriaxone, by increasing the excretion of urinary calcium and crystallizing with calcium, forms stones that obstruct the ureters, resulting in PARF. In addition, the "reflex anuria" mechanism also contributes to this situation.…”