Health-Related Quality of Life Impacts Mortality but Not Progression to End-Stage Renal Disease in Pre-Dialysis Chronic Kidney Disease: A Prospective Observational Study

Background
Chronic kidney disease (CKD) is associated with reduced health-related quality of life (HRQL). However, the relationship between pre-dialysis CKD, HRQL and clinical outcomes, including mortality and progression to end-stage renal disease (ESRD) is unclear.
Methods
All 745 participants recruited into the Renal Impairment In Secondary Care study to end March 2014 were included. Demographic, clinical and laboratory data were collected at baseline including an assessment of HRQL using the Euroqol EQ-5D-3L. Health states were converted into an EQ-5Dindex score using a set of weighted preferences specific to the UK population. Multivariable Cox proportional hazards regression and competing risk analyses were undertaken to evaluate the association of HRQL with progression to ESRD or all-cause mortality. Regression analyses were then performed to identify variables associated with the significant HRQL components.
Results
Median eGFR was 25.8 ml/min/1.73 m2 (IQR 19.6–33.7ml/min) and median ACR was 33 mg/mmol (IQR 6.6–130.3 mg/mmol). Five hundred and fifty five participants (75.7%) reported problems with one or more EQ-5D domains. When adjusted for age, gender, comorbidity, eGFR and ACR, both reported problems with self-care [hazard ratio 2.542, 95% confidence interval 1.222–5.286, p = 0.013] and reduced EQ-5Dindex score [hazard ratio 0.283, 95% confidence interval 0.099–0.810, p = 0.019] were significantly associated with an increase in all-cause mortality. Similar findings were observed for competing risk analyses. Reduced HRQL was not a risk factor for progression to ESRD in multivariable analyses.
Conclusions
Impaired HRQL is common in the pre-dialysis CKD population. Reduced HRQL, as demonstrated by problems with self-care or a lower EQ-5Dindex score, is associated with a higher risk for death but not ESRD. Multiple factors influence these aspects of HRQL but renal function, as measured by eGFR and ACR, are not among them.

背景
慢性肾脏病（Chronic kidney disease, CKD）与健康相关生活质量（Health-related Quality of Life, HRQL）下降密切相关。然而，透析前慢性肾脏病、健康相关生活质量与包括死亡及进展为终末期肾病（End-stage Renal Disease, ESRD）在内的临床结局之间的关联尚不明确。

方法
本研究纳入截至2014年3月纳入二级护理肾损害研究（Renal Impairment In Secondary Care study）的全部745名受试者。于基线时收集人口统计学、临床及实验室数据，其中采用EuroQol EQ-5D-3L量表对健康相关生活质量进行评估。采用英国人群专属的加权偏好集，将健康状态转换为EQ-5D指数得分。采用多变量Cox比例风险回归及竞争风险分析，评估健康相关生活质量与终末期肾病进展或全因死亡的关联。随后开展回归分析，以明确与健康相关生活质量各关键维度相关的变量。

结果
受试者的估算肾小球滤过率（estimated Glomerular Filtration Rate, eGFR）中位数为25.8 ml/min/1.73 m2（四分位距19.6~33.7 ml/min），尿白蛋白/肌酐比值（Albumin Creatinine Ratio, ACR）中位数为33 mg/mmol（四分位距6.6~130.3 mg/mmol）。555名受试者（占比75.7%）存在至少1个EQ-5D维度的健康问题。在校正年龄、性别、合并症、估算肾小球滤过率及尿白蛋白/肌酐比值后，自述存在自理障碍[风险比（hazard ratio, HR）=2.542，95%置信区间（confidence interval, CI）：1.222~5.286，P=0.013]及EQ-5D指数得分降低[HR=0.283，95%CI：0.099~0.810，P=0.019]均与全因死亡风险升高显著相关。竞争风险分析亦得到相似结果。多变量分析显示，健康相关生活质量下降并非终末期肾病进展的危险因素。

结论
透析前慢性肾脏病患者群体中，健康相关生活质量受损十分常见。以自理障碍或较低EQ-5D指数得分体现的健康相关生活质量下降，与死亡风险升高相关，但与终末期肾病进展无关。多种因素可影响健康相关生活质量的上述维度，但以估算肾小球滤过率及尿白蛋白/肌酐比值衡量的肾功能并非此类影响因素。