Disruptions in Tiopronin therapy: impacts on clinical outcomes of pediatric cystinuria patients during the COVID-19 pandemic.

Abstract

Cystinuria, characterized by defective renal absorption of cystine causing recurrent nephrolithiasis, demands ongoing management. This study examines the effects of COVID-19-related disruptions in tiopronin availability on the clinical outcomes of pediatric cystinuria patients. This retrospective cohort study analyzed medical records of 11 pediatric patients with cystinuria, followed from 2001 to 2023. Patients were diagnosed using urine microscopy/biochemistry and stone composition analysis. Clinical outcomes, including renal function and stone status, were assessed using serial ultrasonographic evaluations and 24-hour urinary cystine measurements. At diagnosis, the median age was 13 months, and 63.6% were female. Acute kidney injury was observed in 36.4% of patients, with 27.3% requiring emergency dialysis. The interruption of tiopronin treatment led to significant renal function deterioration and increased stone burden, as evidenced by an increase in the median number of kidney stones from 2 (IQR: 1-3) to 4 (IQR: 2-5, p = 0.045) and a rise in 24-hour urinary cystine levels from 286 mg/1.73 m² (IQR: 82-552.5) to 434 mg/1.73 m² (IQR: 198-854, p = 0.043). Data prior to the interruption showed a median glomerular filtration rate (GFR) of 80.4 mL/min/1.73 m² and creatinine levels of 2.47 mg/dL. After resuming tiopronin, there was a notable improvement to a median GFR of 161 mL/min/1.73 m² and creatinine levels of 0.48 mg/dL. Managing cystinuria during the pandemic underscored the critical role of continuous access to medications like tiopronin in preventing renal deterioration. Developing strategies to ensure an uninterrupted drug supply during global health emergencies is crucial for managing chronic conditions such as cystinuria.