Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

噻唑烷二酮类（Thiazolidinediones, TZDs）可降低糖尿病肾病患者的尿白蛋白排泄量与蛋白尿水平。目前尚不明确TZDs对合并慢性肾脏病（Chronic Kidney Disease, CKD）的糖尿病患者的硬肾脏终点事件的影响。本研究旨在探讨TZDs与晚期慢性肾脏病糖尿病患者长期透析或死亡风险的关联。本研究依托中国台湾地区全民健康保险研究资料库，开展全国性基于人群的队列研究。2000年1月至2009年6月期间，本研究共纳入12350例晚期慢性肾脏病糖尿病患者，其血清肌酐水平＞6mg/dL且尚未接受肾脏替代治疗。本研究采用多变量Cox回归模型与基于倾向得分的匹配技术，分别估算TZDs使用者（n=1224）与非使用者（n=11126）发生长期透析的风险比（hazard ratios, HRs），以及长期透析或死亡的复合终点事件的风险比。中位随访时长为6个月时，共8270例（67.0%）患者需接受长期透析，2593例（21.0%）患者在开始长期透析前死亡。经倾向得分匹配分析后，本研究发现TZDs使用者发生长期透析的风险更低（HR=0.80；95%置信区间[CI]：0.74~0.86），且长期透析或死亡的复合终点事件风险同样显著降低（HR=0.85；95%CI：0.80~0.91）。该结果在多数患者亚组中均保持一致。合并晚期慢性肾脏病的糖尿病患者使用TZDs，与进展至需长期透析的终末期肾病或死亡的风险降低相关。未来仍需开展进一步的随机对照研究以验证这一关联。