Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study

BackgroundThe link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear.MethodsWe studied 367,932 adults (20–93 years old) in the Korean Heart Study (baseline between 1996–2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders.ResultsAlthough cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR 2 and 54.3% for proteinuria ≥1+). Lower eGFR (2) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24–1.78]) and non-CVD/non-cancer causes (1.78 [1.54–2.05]). The risk of cancer mortality only reached significance at eGFR 2 when eGFR 45–59 ml/min/1.73m2 was set as a reference (1.62 [1.10–2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66–2.25]), cancer (1.49 [1.32–1.68]), and other causes (2.19 [1.96–2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.ConclusionLow eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.【背景】 低估算肾小球滤过率（estimated glomerular filtration rate, eGFR）与高水平蛋白尿（proteinuria）和心血管疾病（cardiovascular disease, CVD）死亡率之间的关联已得到广泛证实，但二者与其他原因所致死亡的关联尚不明确。 【方法】 本研究纳入韩国心脏研究中的367932名成年受试者（年龄20~93岁），基线调查于1996年至2004年开展，随访至2011年结束。研究人员在校正潜在混杂因素后，评估了基于肌酐的eGFR与试纸法蛋白尿（dipstick proteinuria）和三类死亡结局的关联：CVD所致死亡（1608例）、癌症所致死亡（4035例），以及其他（非CVD/非癌症）原因所致死亡（3152例）。 【结果】 尽管总体而言癌症是最常见的死亡原因，但在慢性肾脏病（chronic kidney disease, CKD）受试者中，非CVD/非癌症死亡约占总死亡的一半：eGFR分组2的受试者占比为47.0%，蛋白尿≥1+组为54.3%。较低的eGFR（标注为2的分组）与CVD所致死亡（校正后风险比1.49，95%置信区间1.24~1.78）及非CVD/非癌症原因所致死亡（1.78，95%置信区间1.54~2.05）显著相关。当以eGFR 45~59 ml/min/1.73m²作为参照组时，仅在eGFR分组2中，癌症死亡风险才达到统计学显著性（1.62，95%置信区间1.10~2.39）。高水平蛋白尿（试纸法检测结果≥1+与阴性/微量对比）与CVD（1.93，95%置信区间1.66~2.25）、癌症（1.49，95%置信区间1.32~1.68）及其他原因所致死亡（2.19，95%置信区间1.96~2.45）均存在持续的正相关。进一步细化死亡原因亚组分析显示，低eGFR和高水平蛋白尿均与冠心病、各类感染性疾病、糖尿病及肾衰竭所致死亡显著相关。此外，蛋白尿还与卒中、胃癌、肝癌、胰腺癌、肺癌、骨髓瘤、肺炎及病毒性肝炎所致死亡相关。 【结论】 低eGFR与CVD及非CVD/非癌症死亡相关，而高水平蛋白尿则持续与CVD、癌症及其他原因所致死亡相关。本研究结果提示，对于CKD患者，尤其是合并蛋白尿的患者，需制定并实施多学科预防与管理策略。