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Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study

Stefan J Schunk, Alexander Zarbock, Melanie Meersch, et al

Lancet Published:June 12, 2019 DOI:https://doi.org/10.1016/S0140-6736(19)30769-X

Summary

Background 背景

Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss.

心脏手术后发生急性肾损伤(AKI)及后续肾功能丧失的风险很高。我们研究一种肾小管应激标志物（即尿DDK3）术前鉴别AKI及后续肾功能丧失风险患者的临床价值。

Methods 方法

This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed.

这项观察性研究的推导队列与验证队列 (RenalRIP trial) 均为接受心脏手术的患者。研究纳入德国洪堡Saarland大学医学中心连续收治的择期心脏手术患者（推导队列），以及纳入前瞻性RenalRIP多中心试验的接受择期心脏手术的患者（根据Cleveland临床医院评分大于等于6分）（验证队列），后者包括随机分组至远端缺血预处理或假操作组的患者。我们评价了术前尿DKK3浓度与肌酐比值(DKK3:creatinine)与术后AKI（根据KDIGO标准诊断）和后续肾功能丧失（根据eGFR确诊）的相关性。

Findings 结果

In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10–2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23–0·42, p<0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733–910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08–3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67–26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50–122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45–5·37) and persistent renal dysfunction (OR 3·82, 1·32–11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76–2·39 and persistent renal dysfunction OR 1·05, 0·12–9·45).

推导队列共纳入 733 名患者，尿DKK3与肌酐比值超过471 pg/mg与AKI风险增加密切相关（比数比 [OR] 1·65, 95% CI 1·10–2·47, p=0·015），且与基线肾脏功能无关。与临床及其他试验室检查相比，尿DKK3与肌酐比值显著改善AKI预测准确性（重分类改善指标 0·32, 95% CI 0·23–0·42, p<0·0001）。尿DKK3与肌酐比值和出院时及中期随访820天(IQR 733–910)时肾功能较差密切相关. 在RenalRIP试验中，术前尿DKK3与肌酐比值超过471 pg/mg与AKI (OR 1·94, 95% CI 1·08–3·47, p=0·026)，90天后持续性肾功能障碍(OR 6·67, 1·67–26·61, p=0·0072)及透析依赖(OR 13·57, 1·50–122·77, p=0·020)密切相关。仅在假处理组患者，尿DKK3与肌酐比值超过471 pg/mg与 AKI (OR 2·79, 95% CI 1·45–5·37)、持续性肾功能障碍(OR 3·82, 1·32–11·05)密切相关，但在远端缺血预处理组则没有相关性 (AKI OR 1·35, 0·76–2·39；持续肾功能障碍 OR 1·05, 0·12–9·45)。

Interpretation 结论

Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective.

术前尿DKK3是术后AKI及后续肾功能丧失的独立预测因素。尿DKK3可能有助于鉴别那些预防策略有效的患者。

Funding

No study funding.

评论[仅代表个人观点]

• AKI的生物标志物是近年来的研究热点
• 尿液DKK3的主要临床意义在于其对于术后AKI的预测价值；然而，单纯从作者报告的AUROC及OR看，预测准确性并不高，可能是限制临床应用的主要问题
• 单纯追求P值< 0.05与能否用于临床应该是两个不同的问题