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

Abstract

Objective: To investigate the pathophysiological process of ceftriaxone-induced urolithiasis and its associated acute kidney injury (AKI) based on an animal study and summarize the main clinical characteristics based on a Chinese clinical systematic review.

Materials and methods: Male Sprague-Dawley rats were randomly divided into five groups of six each according to different treatments including control; ceftriaxone; ceftriaxone with calcium; calcium; and ceftriaxone, calcium with citrate, respectively. The 24-h urine volume, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured; kidney histological examination and stone analysis were performed. Systematic searches of the Chinese Knowledge Database were conducted for reports on ceftriaxone-induced urolithiasis and AKI. The eligibility of each full-text publication was accessed, and qualified data were extracted and reviewed.

Results: Kidney stones and a significantly low 24-h urine volume with increased high Scr and BUN levels were found in the group that received ceftriaxone combined with calcium. Citrate was able to inhibit these biochemical changes and stone formations. A total of 161 qualified patients were included in the Chinese clinical systematic review: The proportion of ceftriaxone-induced urolithiasis was 21.1, 19.3, 19.3, 39.1 and 1.2 % for ages <3, 3-6, 7-17, 18-60 and >60 years. 72.7 % developed acute kidney injury eventually.

Conclusion: 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.

Keywords: AKI; Ceftriaxone; Urolithiasis.