Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression
Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression
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DOI：
10.1001/jamainternmed.2018.7980
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发表时间：
2019-04-01
影响因子：
39
通讯作者：
Townsend, Raymond R.
中科院分区：
文献类型：
--
作者：
Waikar, Sushrut S.;Srivastava, Anand;Townsend, Raymond R.
草酸盐是一种有潜在毒性的晚期代谢物，主要由肾脏排出。草酸肾病是一种众所周知的罕见遗传性疾病和肠源性高草酸尿的并发症，但草酸尚未被研究作为更常见形式的慢性肾脏疾病（CKD）的潜在因素。目的：评估尿草酸盐排泄是否是CKD快速发展为肾衰竭的危险因素。设计、环境和参与者：这项前瞻性队列研究评估了2003年6月1日至2008年9月30日参加慢性肾功能不全队列研究的3123名2至4期CKD患者。数据分析时间为2017年10月24日至2018年6月17日。24小时尿草酸排泄。主要结局和测量：估计肾小球滤过率（eGFR）和终末期肾病（ESRD）下降50%。结果本研究纳入3123名参与者（平均[SD]年龄59.1[10.6]岁，女性1414人[45.3%]，白人1423人[45.6%]）。24小时尿液采集时的平均eGFR （SD）为42.9 (16.8)mL/min/1.73 m(2)。尿草酸排泄量中位数为18.6mg/24小时（四分位数间距[IQR]为12.9 ~ 25.7mg/24小时），与eGFR呈负相关（r = -0.13, P < 0.001），与24小时蛋白尿呈正相关（r = 0.22, P < 0.001）。在22 318人年的随访中，752人达到ESRD， 940人达到ESRD或eGFR下降50%的复合终点（CKD进展）。较高的草酸排泄与CKD进展和ESRD的风险增加独立相关：与1分位数（草酸排泄，< 11.5mg/24小时）相比，5分位数（草酸排泄，>= 27.8mg/24小时）的CKD进展风险增加33%（风险比[HR]， 1.33; 95% CI, 1.04-1.70）， ESRD风险增加45%（风险比[HR]， 1.45; 95% CI, 1.09-1.93）。草酸排泄与CKD进展和ESRD之间的关联是非线性的，在3至5分位数与1和2分位数之间表现出阈值效应。较高的草酸排泄量与较低的草酸排泄量（第40百分位）相关，CKD进展风险增加32% (HR, 1.32; 95% CI, 1.13-1.53)， ESRD风险增加37% （HR, 1.37; 95% CI, 1.15-1.63）。当将死亡视为竞争事件时，结果相似。结论和相关性较高的24小时尿草酸盐排泄量可能是CKD 2 - 4期患者CKD进展和ESRD的危险因素。
IMPORTANCE Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD).OBJECTIVE To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure.DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018.EXPOSURES Twenty-four-hour urinary oxalate excretion.MAIN OUTCOMES AND MEASURES A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD).RESULTS This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m(2). Median urinary excretion of oxalate was 18.6mg/24 hours (interquartile range [IQR], 12.9-25.7mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P < .001) and positively with 24-hour proteinuria (r = 0.22, P < .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, < 11.5mg/24 hours) those in quintile 5 (oxalate excretion, >= 27.8mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event.CONCLUSIONS AND RELEVANCE Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.