Amoxicillin crystalluria and amoxicillin-induced crystal nephropathy: a narrative review

Amoxicillin crystalluria (AC) refers to the precipitation of amoxicillin in the urine as amoxicillin trihydrate crystals. Amoxicillin-induced crystal nephropathy (AICN) refers to the obstruction of kidney tubules by amoxicillin trihydrate crystals, resulting in acute kidney injury. Usually considered rare and not serious, AC and AICN would be more frequent in patients receiving high-dose i.v. amoxicillin (≥150 mg/kg per day) than previously reported. AC prevalence ranges from 24% to 41%. AICN prevalence remains unclear. AC is generally asymptomatic, but sudden macroscopic hematuria with cloudy urine suggests the diagnosis. AC is diagnosed by detecting amoxicillin trihydrate crystals in urine. AC is a risk factor for acute kidney injury. Diagnosing AICN is more challenging in the absence of noninvasive diagnostic tools. It is suspected in high-dose i.v. amoxicillin-treated patients who develop acute kidney injury and AC, and after excluding other causes of acute kidney injury (mainly sepsis and acute interstitial nephritis). When testing for AC is unavailable, the presence of demonstrated (high blood amoxicillin levels and low urinary pH) or suspected (rapid i.v. amoxicillin administration and hypovolemia) risk factors for AC suggests its diagnosis. AICN management includes discontinuation/reduction of amoxicillin doses and volume resuscitation to improve tubular flow and urine output and decrease amoxicillin supersaturation. Patients generally recover normal kidney function rapidly after stopping amoxicillin, but renal replacement therapy is required in 10%-40% of patients. No deaths have been directly attributed to AICN. Future studies are needed to assess the exact prevalence of AC/AICN and to define optimal therapeutic options.