Supplementary Material for: Increased risk of end-stage kidney disease in patients with chronic kidney disease and heart failure with reduced ejection fraction

Introduction: The prevalence of heart failure (HF) is more common in people with advanced non-dialysis chronic kidney disease (ND-CKD). It is well known that HF with reduced ejection fraction (HFrEF) is associated with a higher risk of mortality in people with ND-CKD compared to the general population. However, the impact of HFrEF on progression into end-stage kidney disease (ESKD) is not well studied. Our study aimed to examine the independent association of HFrEF on progression to ESKD after correcting for confounding factors using two methods of propensity scoring.
Methods: This study used data from the Salford Kidney Study, a longitudinal study which has recruited more than 3000 patients with ND-CKD since 2002. Patients without a history of HF during the recruitment questionnaire were included in the control group. Patients with a reported history of HF and echo showing left ventricular ejection fraction <40% at enrolment were included in the HFrEF group. Two propensity score methods were used to attenuate the effects of confounding factors between the two groups – propensity score matching (PSM) and inverse probability weighting (IPW). Univariate and multivariate Cox regression analyses were performed.
Results: A total of 2383 patients were included in the analysis. Patients with HFrEF had significantly higher median age and a higher percentage of male gender compared to patients with no HF (72.5 vs 66.6 years and 71.8% vs 61.1% respectively). Univariate and 5 models of multivariate Cox regression analysis showed that HFrEF in people with CKD was a strong predictor for a higher incidence of ESKD (model 5: HR 1.38; 95% CI = 1.01-1.90; p = 0.044). The association between HFrEF and the risk of ESKD remained significant after using the PSM and the IPW methods.
Conclusion: Patients with concomitant advanced ND-CKD and prevalent HFrEF were found to have a higher risk of ESKD when compared to patients with no HF. This risk persists despite the adjustment of confounding factors using PSM and IPW.

引言：心力衰竭(heart failure, HF)在晚期非透析慢性肾脏病(non-dialysis chronic kidney disease, ND-CKD)患者中更为普遍。众所周知，与普通人群相比，射血分数降低型心力衰竭(heart failure with reduced ejection fraction, HFrEF)会使ND-CKD患者的死亡风险升高。然而，目前针对HFrEF对患者进展为终末期肾病(end-stage kidney disease, ESKD)的影响研究尚少。本研究旨在通过两种倾向得分(propensity scoring)校正混杂因素后，探究HFrEF与ESKD进展之间的独立关联。
方法：本研究使用索尔福德肾脏病研究(Salford Kidney Study)的数据，该队列研究自2002年起已招募超过3000名ND-CKD患者。研究纳入招募问卷中无心力衰竭病史的患者作为对照组；纳入入组时自述有心力衰竭病史且超声心动图显示左心室射血分数<40%的患者作为HFrEF组。本研究采用两种倾向得分方法——倾向得分匹配(propensity score matching, PSM)与逆概率加权(inverse probability weighting, IPW)——以校正两组间的混杂因素影响，并开展单因素与多因素Cox回归分析(Cox regression analysis)。
结果：本研究共纳入2383例患者进行分析。与无心力衰竭病史的患者相比，HFrEF组患者的中位年龄更高，男性占比也更大（中位年龄：72.5岁 vs 66.6岁；男性占比：71.8% vs 61.1%）。单因素及5项多因素Cox回归分析结果显示，慢性肾脏病患者合并HFrEF是ESKD发病率升高的强预测因子（模型5：风险比(hazard ratio, HR)=1.38；95%置信区间(confidence interval, CI)=1.01~1.90；p=0.044）。采用PSM与IPW方法校正后，HFrEF与ESKD风险之间的关联仍具有统计学意义。
结论：与无心力衰竭病史的晚期ND-CKD患者相比，合并HFrEF的晚期ND-CKD患者进展为ESKD的风险更高。且该风险在采用PSM与IPW校正混杂因素后依然存在。