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

ABSTRACT: Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/?-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.

SUBMITTER: Yang X

PROVIDER: S-EPMC5661292 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Yang Xiaobing X Chen Chunbo C Teng Siyuan S Fu Xiaorui X Zha Yan Y Liu Huafeng H Wang Li L Tian Jianwei J Zhang Xiangyan X Liu Youhua Y Nie Jing J Hou Fan Fan FF

Journal of the American Society of Nephrology : JASN 20170711 11

Urinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/<i>β</i>-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 ...[more]

PMID: 28698269

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Project description:Background and objectivesAKI is a serious complication after cardiac surgery. Although high urinary concentrations of the tubular protein uromodulin, a marker of tubular health, are associated with less AKI in animal models, its relationship in humans is unknown.Design, setting, participants, & measurementsA post hoc analysis of a prospective cohort study of 218 adults undergoing on-pump cardiac surgery between 2004 and 2011 was conducted. Multivariable logistic and linear regression analyses were used to evaluate the associations of preoperative urinary uromodulin-to-creatinine ratio with postoperative AKI (defined as a rise in serum creatinine of >0.3 mg/dl or >1.5 times baseline); severe AKI (doubling of creatinine or need for dialysis) and peak postoperative serum creatinine over the first 72 hours.ResultsMean age was 68 years, 27% were women, 95% were white, and the median uromodulin-to-creatinine ratio was 10.0 ?g/g. AKI developed in 64 (29%) patients. Lower urinary uromodulin-to-creatinine ratio was associated with higher odds for AKI (odds ratio, 1.49 per 1-SD lower uromodulin; 95% confidence interval, 1.04 to 2.13), which was marginally attenuated after multivariable adjustment (odds ratio, 1.43; 95% confidence interval, 0.99 to 2.07). The lowest uromodulin-to-creatinine ratio quartile was also associated with higher odds for AKI relative to the highest quartile (odds ratio, 2.94; 95% confidence interval, 1.19 to 7.26), which was slightly attenuated after multivariable adjustment (odds ratio, 2.43; 95% confidence interval, 0.91 to 6.48). A uromodulin-to-creatinine ratio below the median was associated with higher adjusted odds for severe AKI, although this did not reach statistical significance (odds ratio, 4.03; 95% confidence interval, 0.87 to 18.70). Each 1-SD lower uromodulin-to-creatinine ratio was associated with a higher adjusted mean peak serum creatinine (0.07 mg/dl per SD; 95% confidence interval, 0.02 to 0.13).ConclusionsLower uromodulin-to-creatinine ratio is associated with higher odds of AKI and higher peak serum creatinine after cardiac surgery. Additional studies are needed to confirm these preliminary results.

Project description:Importance:Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear. Objective:To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes. Design, Setting, and Participants:This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery. Exposures:Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery. Main Outcomes and Measures:Hypertension (blood pressure ?95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria). Results:Overall, 131 children (median [interquartile range] age, 7.7 [5.9-9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI. Conclusions and Relevance:Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension.

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

Publications

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

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