Characterizing ceftriaxone-induced urolithiasis and its associated acute kidney injury: an animal study and Chinese clinical systematic review

Abstract

Ceftriaxone-induced urolithiasis was associated with a high risk of AKI. The pathophysiological process may be related to urinary obstruction and crystalline nephropathy. Citrate was able to inhibit stone formation and prevent further kidney injury.

Drug-Induced Urolithiasis in Pediatric Patients

“…It is considered the most common lithogenic antibacterial drug in the pediatric population, with an incidence ranging from 0.6% [45] to 8.3% [31]. A systematic review of 161 Chinese patients analyzing the age distribution of patients with ceftriaxoneinduced urolithiasis showed that 21.1%, 19.3%, and 19.3% of those patients were < 3, 3-6, and 7-17 years old, respectively (overall 59.7% for the pediatric population from 0 to 17 years old), compared to 40.3% in the adult population, demonstrating a predominance of this side effect in pediatric patients [46].…”

“…This may be the underlying mechanism for its biliary side effects [29]; however, the mechanism of ceftriaxone-induced nephrolithiasis is not yet completely understood [31]. In this setting, several authors have tried to investigate the pathophysiological mechanism for ceftriaxone-associated renal side effects [24,46]. Zhang et al [46] demonstrated in their animal study that the rats that were administered ceftriaxone and calcium showed a significantly lower volume of 24-h urine, with a significant increase in serum creatinine and blood urea nitrogen levels, suggesting that calcium chloride is important for stone formation.…”

“…In this setting, several authors have tried to investigate the pathophysiological mechanism for ceftriaxone-associated renal side effects [24,46]. Zhang et al [46] demonstrated in their animal study that the rats that were administered ceftriaxone and calcium showed a significantly lower volume of 24-h urine, with a significant increase in serum creatinine and blood urea nitrogen levels, suggesting that calcium chloride is important for stone formation. This is in contrast to Avci et al [33], who reported unchanged calcium excretion in children treated with ceftriaxone.…”

Unravelling Pathophysiology of Crystalline Nephropathy in Ceftriaxone-Associated Acute Kidney Injury: A Cellular Proteomic Approach

“…However, its underlying mechanisms at cellular levels have remained unknown. Recently, Zhang et al [12], showed that ceftriaxone could induce nephropathy in an animal model of ceftriaxone nephrolithiasis. The gross specimens showed numerous sand-liked ceftriaxone calculi deposited in renal parenchyma and histology showed renal tubules with swollen epithelial cells but normal glomeruli [12].…”

“…Recently, Zhang et al [12], showed that ceftriaxone could induce nephropathy in an animal model of ceftriaxone nephrolithiasis. The gross specimens showed numerous sand-liked ceftriaxone calculi deposited in renal parenchyma and histology showed renal tubules with swollen epithelial cells but normal glomeruli [12]. This evidence in vivo corresponded with our previous study in which ceftriaxone-calcium (Cef-Ca) crystals could tightly adhere onto renal tubular cells [13].…”