德国萨兰大学医学中心Thimoteus Speer课题组探讨了尿dickkopf-3与心脏手术患者急性肾损伤（AKI）及后续肾功能丧失之间的关系。相关论文发表在2019年8月10日出版的《柳叶刀》杂志上。

该课题组探讨了尿dickkopf-3 （DKK3）作为肾小管应激标志物用于术前识别有AKI及肾功能丧失风险患者的临床应用价值。

该观察性队列研究包括衍生队列和验证队列（RenalRIP试验）中进行心脏手术的患者，评估术前尿中DKK3与肌酐的比值（DKK3：肌酐）与术后AKI以及后续肾功能丧失的关系。

在衍生队列的733例患者中，尿中DKK3：肌酐浓度高于471 pg/mg，AKI风险显著增加，且与基线肾功能无关。与临床和其他实验室测量指标相比，尿中DKK3：肌酐可显著提高AKI预测的准确性。高尿DKK3：肌酐浓度的患者在出院时和中位随访820天后肾功能显著降低。验证试验显示，术前尿DKK3：肌酐浓度高于471 pg/mg的患者与低于471 pg/mg的患者相比，术后90天患AKI、持续肾功能障碍和透析依赖的风险更高。

术前尿DKK3可作为术后AKI和肾功能丧失的独立预测因子。尿DKK3可帮助鉴别有风险的患者，并对其采取预防性的治疗策略。

据介绍，心脏手术与术后急性肾损伤(AKI)和后续肾功能丧失的高风险密切相关。

附：英文原文

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

Author: Stefan J Schunk, MD, Prof Alexander Zarbock, MD,  Melanie Meersch, MD, Mira Küllmar, MD, Prof John A Kellum, MD, David Schmit, MD, Martina Wagner, BS, Sarah Triem, MSc, Prof Stefan Wagenpfeil, PhD, Prof Hermann-Josef Gröne, MD, Prof Hans-Joachim Schäfers, MD, Prof Danilo Fliser, MD, Thimoteus Speer, PhD , Stephen Zewinger, MD

Issue&Volume: VOLUME 394, ISSUE 10197, P488-496, AUGUST 10, 2019

Summary:

Background

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.

Methods

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.

Findings

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).

Interpretation

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.

DOI: DOI:https://doi.org/10.1016/S0140-6736(19)30769-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30769-X/fulltext