Ceftriaxone Linked to Renal Failure in Children

Veronica Hackethal, MD

March 24, 2014

Ceftriaxone used at therapeutic doses is linked to renal stones and pediatric acute renal failure (PARF), with recovery possible on early treatment, according to a retrospective study published online March 24 in Pediatrics.

"Ceftriaxone therapy in children may cause PARF," the authors note, "Early diagnosis and prompt pharmacological therapy are important in relieving the condition. Retrograde ureteral catheterization is an effective treatment for those who fail to respond to pharmacotherapy."

Ceftriaxone, an antibiotic commonly used to treat childhood infections, has been linked to biliary pseudolithiasis, nephrolithiasis, and bladder sludge, according to background information described in the article. Formation of urine crystals that cling to renal tubular cells has been observed during ceftriaxone treatment, with the potential for causing acute renal failure. Few studies have reported on ceftriaxone-associated PARF, however, and its incidence is presumably rare, according to the authors.

The researchers looked at 31 cases of PARF after treatment with ceftriaxone from January 1, 2003, to June 30, 2012, at Tongji Hospital, Wuhan, China. Children with no previous history of urolithiasis or nephropathy were included. Ceftriaxone treatment was verified from 9 patient records and by parent report in 22 children. PARF diagnosis was based on symptomatology (sudden onset anuria, flank or renal percussion pain) and laboratory values (serum creatinine and/or urea nitrogen). Pharmacotherapy included spasmolysis with anisodamine, alkalization with sodium bicarbonate, antibiotics, albumen, and low-dose dexamethasone.

The mean age of included children was 5.1 years. Ceftriaxone was administered, on average, for 5.2 days before PARF onset. Doses were available in 13 cases and ranged from 70 to 100 mg/kg per day (mean, 86.7 mg/kg per day). Predominant symptoms included sudden-onset anuria for at least 24 hours (31/31), flank pain (>3 years, 25/25), excessive crying (<3 years, 6/6), and/or vomiting (19/31). On ultrasound, there was mild hydronephrosis in 25 of 31 children and ureteric calculi in 11 of 31.

After 1 to 4 days of pharmacotherapy, 9 children recovered. Twenty-one children resistant to pharmacotherapy received retrograde ureteral catheterization, after which normal urine flow resumed in 20. One child had dense calculi that impeded catheterization, requiring 3 sessions of hemodialysis to restore urination. Calculi could be recovered from 4 children, and tandem mass spectrometric analysis revealed the main component to be ceftriaxone. Mean treatment duration was 1.8 days, with a mean anuria period of 3.1 days. Ultimately, all children recovered.

Limitations of the study included its small sample size, retrospective design, and incomplete data on ceftriaxone dosage. In addition, the sand-grain nature of ceftriaxone calculi made them difficult to collect, and calculi were only recoverable in 4 patients.

On the basis of this study, the authors advise that observation of sudden-onset anuria or flank pain in children receiving ceftriaxone should prompt its immediate discontinuation, further evaluation with blood tests and ultrasound, and early treatment on confirmation of the diagnosis.

"These results indicate that ceftriaxone-associated PARF is reversible and has a good prognosis if prompt and proper treatments are administered in time," write the authors.

Whether this study could generalize to the United States, however, is open to question, according to Keefe Davis, MD, a pediatric nephrologist at Washington University School of Medicine in St. Louis, Missouri, as the pharmacotherapy used in the study is unavailable in the United States or is unconventional by US standards. This study used a Chinese herbal medicine as an antispasmodic. This likely led to a high use of retrograde ureteroscopy without extracorporeal shockwave lithotripsy, which is commonly used in the United States, according to Dr. Davis. This difference could also limit the study's generalizability.

Dr. Davis noted, however, that this study may potentially bring to light an unappreciated cause of anuric acute kidney failure.

"The literature to date is limited to case report," Dr. Davis explained, "Studies report ceftriaxone kidney stones occur in about 1% of treated patients, but they mostly remain asymptomatic with spontaneous resolution on follow up renal ultrasound."

"Because of the limited knowledge of this complication, prevention measures are not known. Theoretically, avoiding dehydration and providing [intravenous] hydration would be beneficial to maintain urine flow," Dr. Davis pointed out, "Avoidance of calcium supplementation during hospitalization is recommended. A low-sodium diet may help, as well as thiazide diuretics. Ultimately, further studies of interventions will be necessary to learn how to avoid ceftriaxone stone formation."

The authors and Dr. Davis have disclosed no relevant financial relationships.

Pediatrics. Published online March 24, 2014. Abstract

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