Abhishek Abhishek, Nakafero Georgina, Card Tim, Taal Maarten W, Grainge Matthew J, Aithal Guruprasad P, Mallen Christian D, Stevenson Matthew D, Riley Richard D
Academic Rheumatology, University of Nottingham, Nottingham, East Midlands, UK.
Nottingham NIHR BRC, Nottingham, UK.
BMJ Open Gastroenterol. 2025 Jan 25;12(1):e001627. doi: 10.1136/bmjgast-2024-001627.
To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity.
This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination.
13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively.
This prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity.
开发并验证一种用于对5-氨基水杨酸肾毒性进行风险分层监测的预后模型。
这项英国回顾性队列研究分别使用临床实践研究数据链Aurum和Gold的数据进行模型开发和验证。研究纳入了2007年1月1日至2019年12月31日期间新诊断为炎症性肠病并开始接受5-氨基水杨酸（5-ASA）治疗的成年人。与5-ASA肾毒性相关的药物停用定义为肾功能下降且处方间隔≥90天，以此作为研究结局。接受5-ASA治疗≥6个月的患者随访长达5年。采用惩罚Cox回归来建立风险方程，并通过自抽样法进行内部验证和乐观度调整。从校准和区分度方面评估模型性能。
13728名和7318名参与者分别贡献了40378和20679人年的随访数据，构成了开发队列和验证队列，分别有170例（1.2%）和98例（1.3%）结局事件。最终模型纳入了9个预测因素，包括慢性肾脏病3期和有害饮酒作为强预测因素。年龄和体重指数是弱预测因素。开发数据和验证数据中经乐观度调整后的校准斜率、C统计量和D统计量分别为0.90、0.64和0.98，以及1.01、0.66和0.94。
该预后模型利用了常规临床护理信息，在独立验证队列中表现良好。它可用于在既定的5-ASA治疗期间对血液检测监测进行风险分层。一个关键局限性是肾功能下降可能是由5-ASA肾毒性以外的因素导致的。
