Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA Intern Med. 2019 Apr 1;179(4):542-551. doi: 10.1001/jamainternmed.2018.7980.
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).
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.
Twenty-four-hour urinary oxalate excretion.
A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD).
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 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/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, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/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.
Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.
草酸盐是一种潜在的毒性终末代谢产物，主要通过肾脏排泄。草酸肾病是罕见遗传疾病和肠源性高草酸尿症的已知并发症，但草酸是否是更常见的慢性肾脏病 (CKD) 的潜在致病因素尚未得到研究。
评估尿草酸盐排泄是否是 CKD 向肾衰竭更快速进展的危险因素。
设计、地点和参与者：这项前瞻性队列研究评估了 2003 年 6 月 1 日至 2008 年 9 月 30 日期间参加慢性肾功能不全队列研究的 3123 名 2 至 4 期 CKD 患者。数据分析于 2017 年 10 月 24 日至 2018 年 6 月 17 日进行。
24 小时尿草酸盐排泄。
eGFR 下降 50%和终末期肾病 (ESRD)。
这项研究包括 3123 名参与者（平均[标准差]年龄 59.1[10.6]岁；1414[45.3%]名女性；1423[45.6%]名白人）。收集 24 小时尿液时的平均（标准差）eGFR 为 42.9[16.8]mL/min/1.73 m2。中位数尿草酸盐排泄量为 18.6mg/24 小时（四分位距[IQR]，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 22318 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）。较高的草酸盐排泄与 CKD 进展和 ESRD 的风险增加独立相关：与第 1 五分位（草酸盐排泄，<11.5mg/24 小时）相比，第 5 五分位（草酸盐排泄，≥27.8mg/24 小时）的 CKD 进展风险高 33%（风险比[HR]，1.33；95%CI，1.04-1.70），ESRD 风险高 45%（HR，1.45；95%CI，1.09-1.93）。草酸盐排泄与 CKD 进展和 ESRD 之间的关系是非线性的，在第 3 至 5 五分位与第 1 和第 2 五分位之间存在阈值效应。与较低的草酸盐排泄相比（第 40 百分位），CKD 进展的风险高 32%（HR，1.32；95%CI，1.13-1.53），ESRD 的风险高 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。
24 小时尿草酸盐排泄量较高可能是 2 至 4 期 CKD 患者 CKD 进展和 ESRD 的危险因素。
