Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.

中文翻译：

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评估与肾小球疾病的不同免疫抑制治疗相关的心血管事件风险


肾小球疾病患者患心血管疾病的风险很高，但免疫抑制对这种风险的影响尚不清楚。在这项对来自加拿大不列颠哥伦比亚省的 1912 名患者（包括 759 名 IgA 肾病患者、540 名局灶节段性肾小球硬化患者、387 名膜性肾病患者和 226 名微小病变肾病患者）的回顾性队列研究中，我们评估了暴露于特定免疫抑制药物与包括冠状动脉、脑血管和外周动脉事件在内的复合结果之间的关联。根据基线心血管危险因素、肾小球疾病类型、估计肾小球滤过率 （eGFR） 和蛋白尿随时间调整生存模型。在中位随访 6.8 年期间，212 例患者 （11.1%） 经历了主要结局。在调整心血管危险因素后，皮质类固醇暴露与主要结局无显著相关性。在完全调整的模型中，适度（150-300 个定义日剂量 [DDD]）和较高（300 个或更多 DDD）剂量的累积钙调磷酸酶抑制剂暴露与心血管事件风险高 2 倍相关 （风险比 2.98,95% 置信区间 1.27-6.95） 和 （2.78,1.32-5.84），分别。在调整基线危险因素和肾小球疾病类型后，抗代谢物 （硫唑嘌呤、吗替麦考酚酯和麦考酚酯钠） 的每日峰值剂量为 0.5 或更高，与心血管事件风险增加相关，但在调整时变 eGFR 和蛋白尿后则不相关 （1.70， 0.91-3.20）。在完全调整的模型中，每 10 克累积环磷酰胺暴露与心血管事件风险增加 1.5 倍相关 （1.46， 1.22-1.75） 因此，我们的研究结果表明，用于治疗肾小球疾病的免疫抑制疗法可能具有不同的心血管风险概况，在决定个体患者的免疫抑制时应考虑这一点，并作为未来临床试验的安全终点。