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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.
The Lancet ( IF 98.4 ) Pub Date : 2019-06-12 , DOI: 10.1016/s0140-6736(19)30769-x Stefan J Schunk 1 , Alexander Zarbock 2 , Melanie Meersch 2 , Mira Küllmar 2 , John A Kellum 3 , David Schmit 1 , Martina Wagner 1 , Sarah Triem 1 , Stefan Wagenpfeil 4 , Hermann-Josef Gröne 5 , Hans-Joachim Schäfers 6 , Danilo Fliser 1 , Thimoteus Speer 1 , Stephen Zewinger 7
The Lancet ( IF 98.4 ) Pub Date : 2019-06-12 , DOI: 10.1016/s0140-6736(19)30769-x Stefan J Schunk 1 , Alexander Zarbock 2 , Melanie Meersch 2 , Mira Küllmar 2 , John A Kellum 3 , David Schmit 1 , Martina Wagner 1 , Sarah Triem 1 , Stefan Wagenpfeil 4 , Hermann-Josef Gröne 5 , Hans-Joachim Schäfers 6 , Danilo Fliser 1 , Thimoteus Speer 1 , Stephen Zewinger 7
Affiliation
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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.
FUNDING
No study funding.
中文翻译：
心脏手术患者的尿dickkopf-3，急性肾损伤和随后肾功能丧失之间的关联：一项观察性队列研究。
背景技术心脏手术与术后急性肾损伤（AKI）和随后肾功能丧失的高风险相关。我们探讨了尿液dickkopf-3（DKK3）（一种肾小管应激标志物）的临床实用性，用于术前鉴定有AKI风险和随后肾功能丧失风险的患者。方法这项观察性队列研究包括在衍生队列中进行了心脏手术的患者和在验证队列中进行了心脏手术的患者（RenalRIP试验）。该研究包括在萨尔大学医学中心（德国洪堡，德国）连续进行择期心脏手术的患者。参加前瞻性RenalRIP多中心试验（验证队列）并接受随机心脏远程缺血预处理或假手术的患者以及接受择期心脏手术的患者（根据Cleveland Clinical Foundation得分为6或更高选择）程序。评估术前尿中DKK3与肌酐的比例（DKK3：肌酐）与术后AKI（根据肾病改善总体疗效标准）定义的相关性，以及随后的肾功能丧失（通过估计的肾小球滤过率确定）之间的关联。结果在派生队列的733例患者中，尿DKK3对肌酐的尿浓度高于471 pg / mg与AKI风险显着增加有关（比值比[OR] 1·65，95％CI 1·10-2·47，p = 0·015），与基线肾功能无关。与临床和其他实验室测量结果相比，尿中DKK3：肌酐的浓度显着改善了AKI预测（净重分类改善0·32，95％CI 0·23-0·42，p <0·0001）。高尿DKK3：肌酐浓度与出院时以及中位随访820天后的肾功能显着降低独立相关（IQR 733-910）。在RenalRIP试验中，术前尿DKK3：肌酐浓度高于471 pg / mg与AKI的风险显着相关（OR 1·94，95％CI 1·08-3·47，p = 0·026）， 90天后持续存在肾功能不全（OR 6·67，1·67-26·61，p = 0·0072）和透析依赖性（OR 13·57，1·50-122·77，p = 0·020）与DKK3相比：肌酐浓度为471 pg / mg或更低。尿DKK3：肌酐浓度高于471 pg / mg与AKI（OR 2·79，95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32- 11·05）仅适用于具有假手术的患者，而不适用于远程缺血预处理（AKI或1·35、0·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32-11·05）仅适用于假手术患者，而非远程缺血预处理（AKI OR 1·35，0 ·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32-11·05）仅适用于假手术患者，而非远程缺血预处理（AKI OR 1·35，0 ·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。资助没有研究资助。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。尿DKK3可能有助于识别预防性治疗策略有效的患者。资助没有研究资助。
更新日期：2019-08-09
中文翻译：
心脏手术患者的尿dickkopf-3，急性肾损伤和随后肾功能丧失之间的关联：一项观察性队列研究。
背景技术心脏手术与术后急性肾损伤（AKI）和随后肾功能丧失的高风险相关。我们探讨了尿液dickkopf-3（DKK3）（一种肾小管应激标志物）的临床实用性，用于术前鉴定有AKI风险和随后肾功能丧失风险的患者。方法这项观察性队列研究包括在衍生队列中进行了心脏手术的患者和在验证队列中进行了心脏手术的患者（RenalRIP试验）。该研究包括在萨尔大学医学中心（德国洪堡，德国）连续进行择期心脏手术的患者。参加前瞻性RenalRIP多中心试验（验证队列）并接受随机心脏远程缺血预处理或假手术的患者以及接受择期心脏手术的患者（根据Cleveland Clinical Foundation得分为6或更高选择）程序。评估术前尿中DKK3与肌酐的比例（DKK3：肌酐）与术后AKI（根据肾病改善总体疗效标准）定义的相关性，以及随后的肾功能丧失（通过估计的肾小球滤过率确定）之间的关联。结果在派生队列的733例患者中，尿DKK3对肌酐的尿浓度高于471 pg / mg与AKI风险显着增加有关（比值比[OR] 1·65，95％CI 1·10-2·47，p = 0·015），与基线肾功能无关。与临床和其他实验室测量结果相比，尿中DKK3：肌酐的浓度显着改善了AKI预测（净重分类改善0·32，95％CI 0·23-0·42，p <0·0001）。高尿DKK3：肌酐浓度与出院时以及中位随访820天后的肾功能显着降低独立相关（IQR 733-910）。在RenalRIP试验中，术前尿DKK3：肌酐浓度高于471 pg / mg与AKI的风险显着相关（OR 1·94，95％CI 1·08-3·47，p = 0·026）， 90天后持续存在肾功能不全（OR 6·67，1·67-26·61，p = 0·0072）和透析依赖性（OR 13·57，1·50-122·77，p = 0·020）与DKK3相比：肌酐浓度为471 pg / mg或更低。尿DKK3：肌酐浓度高于471 pg / mg与AKI（OR 2·79，95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32- 11·05）仅适用于具有假手术的患者，而不适用于远程缺血预处理（AKI或1·35、0·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32-11·05）仅适用于假手术患者，而非远程缺血预处理（AKI OR 1·35，0 ·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。95％CI 1·45-5·37）和持续性肾功能不全（OR 3·82，1·32-11·05）仅适用于假手术患者，而非远程缺血预处理（AKI OR 1·35，0 ·76-2·39和持续性肾功能不全或1·05、0·12-9·45）。解释术前尿DKK3是术后AKI和随后肾功能丧失的独立预测因子。尿DKK3可能有助于识别预防性治疗策略有效的患者。资助没有研究资助。尿DKK3可能有助于识别预防性治疗策略有效的患者。经费没有研究经费。尿DKK3可能有助于识别预防性治疗策略有效的患者。资助没有研究资助。
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