Incidence and risk factors for calcification after dextranomer/hyaluronic acid (Dx/HA) copolymer injection for vesicoureteral reflux

Abstract

Since the first case of dextranomer/hyaluronic acid (Dx/HA) implant calcification in 2008, concern about the long-term sequelae of Dx/HA injection has been growing. According to previous reports, the incidence of Dx/HA calcification 4 years after injection would be around 2%. The primary aim was to estimate the incidence of Dx/HA implant calcification after endoscopic treatment of vesicoureteral reflux in pediatric patients. Secondary objectives were to establish risk factors and to perform a survival analysis after Dx/HA injection. Patients undergoing Dx/HA endoscopic injection from 2007 to 2014 were prospectively registered. The database included clinical, surgical and radiological outcomes. Patients that showed Dx/HA implant calcification during follow-up were compared to those who did not. Univariable and survival statistical analyses were performed. 30 implants calcified over 355 ureters endoscopically treated. Age at first treatment was lower in patients with implant calcification (2.4±1.3 years vs 3.6±2.5 years; p<0.005). The risk of implant calcification was 8.45% (95% CI: 5.96-11.85%). Median follow-up was 7.6 years (IQR: 5.2-9.5). The incidence rate was 12.06 cases per 1000 ureters-year. The period of highest hazard of implant calcification was between 3 and 5 years after injection. The only risk factor related to implant calcification was the age at first injection: relative risk of implant calcification was 4.4 (95% CI: 1.6 to 12.4; p=0.002) for patients first treated before the age of 3.5 years. The risk and the incidence rate of Dx/HA implant calcification were higher than previous data. The period of highest hazard and detection of implant calcification were consistent with previous reports. Patients first treated before the age of 3.5 had shorter survival time without implant calcification. These are the first data about risk factors and survival function of Dx/HA implant calcification. However, our conclusions about the clinical significance of Dx/HA implant calcification were limited because the patients with implant calcification were asymptomatic. Further studies with larger sample and longer follow-up should confirm the clinical significance and life-long tendency of Dx/HA implant calcification. The risk and the incidence rate of Dx/HA implant calcification were higher than expected. The hazard of calcification was higher between 3 and 5 years after injection. The risk was especially higher in patients treated before the age of 3.5. Caution should be taken not to confuse implant calcifications with ureteric stones. A 5-year follow-up would set a better understanding of the actual incidence and clinical significance of implant calcification.