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J Am Soc Nephrol. 2017 Nov;28(11):3373-3382. doi: 10.1681/ASN.2017020142. Epub 2017 Jul 11.

Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after Cardiac Surgery.

Author information

1
Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China.
2
Department of Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, China.
3
Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang Medical University, Guiyang, China.
4
Division of Nephrology, Institute of Nephrology, Guangdong Medical College, Zhanjiang, China; and.
5
Division of Nephrology, Sichuan Provincial People's Hospital, Chengdu, China.
6
Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangzhou, China; ffhouguangzhou@163.com.

Abstract

Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/β-catenin, which is activated in AKI models. To test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after cardiac surgery, we performed a prospective, multicenter, two-stage cohort study in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children from three academic medical centers. In stage 2, we enrolled 398 adults at six centers. We analyzed levels of uMMP-7 and other injury biomarkers during the perioperative period. Severe AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3. uMMP-7 level peaked within 6 hours after surgery in patients who subsequently developed severe AKI. After multivariate adjustment, the highest quintile of postoperative uMMP-7 level, compared with the lowest quintile, associated with 17-fold (in adults) and 36-fold (in children) higher odds of severe AKI. Elevated uMMP-7 level associated with increased risk of composite events (severe AKI, acute dialysis, and in-hospital death) and longer stay in the intensive care unit and hospital. For predicting severe AKI, uMMP-7 had an area under the receiver operating characteristic curve of 0.81 (in children) and 0.76 (in adults), outperforming urinary IL-18, angiotensinogen, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, and tissue inhibitor of metalloproteinase-2·IGF-binding protein-7 and the clinical model. uMMP-7 significantly improved risk reclassification over the clinical model alone, as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, uMMP-7 is a promising predictor for severe AKI and poor in-hospital outcomes in patients after cardiac surgery.

KEYWORDS:

Acute Kidney Injury; Biomarker; Cardiac Surgery; Matrix Metalloproteinase-7

PMID:
28698269
PMCID:
PMC5661292
DOI:
10.1681/ASN.2017020142
[Indexed for MEDLINE]
Free PMC Article

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