Urinary EGF and MCP-1 and risk of CKD after cardiac surgery

Menez, Steven; Ju, Wenjun; Menon, Rajasree; Moledina, Dennis G.; Thiessen-Philbrook, Heather; McArthur, Eric; Jia, Yaqi; Obeid, Wassim; Mansour, Sherry G.; Koyner, Jay L.; Shlipak, Michael G.; Coca, Steven G.; Garg, Amit X.; Bomback, Andrew S.; Kellum, John A.; Kretzler, Matthias; Parikh, Chirag R.

doi:10.1172/jci.insight.147464

Cited by 28 publications

(24 citation statements)

References 65 publications

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“…The CCL2 gene that encodes MCP-1 is expressed primarily in the ascending loop of Henle and distal tubule 41 . Higher levels of both plasma and urinary MCP-1 were shown to be important biomarkers of AKI 42 , 43 , and we have previously shown that gene expression of CCL2 and urinary MCP-1 levels are elevated in the setting of cardiac surgery-associated AKI 44 . Higher urinary MCP-1 levels also associated with chronic tubule-interstitial damage and CKD progression in various settings such as IgA nephropathy, diabetes mellitus, and obstructive uropathy 41 , 45 , 46 , 47 .…”

Section: Discussionmentioning

confidence: 79%

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

Menez

Moledina

Thiessen-Philbrook

et al. 2022

American Journal of Kidney Diseases

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Rationale and Objective Acute kidney injury (AKI) is common in patients with COVID-19 and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers with adverse kidney outcomes among patients hospitalized with COVID-19. Study Design Prospective cohort study. Setting and Participants Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. Exposures 19 urinary biomarkers of injury, inflammation, and repair. Outcomes Composite of KDIGO stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. Analytic Approach Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. Results Out of 153 patients, 24 (15.7%) experienced the primary outcome. Two-fold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR: 1.34; 95% CI: 1.14-1.57), monocyte chemoattractant protein (MCP-1) (HR: 1.42; 95% CI: 1.09-1.84), and kidney injury molecule-1 (KIM-1) (HR: 2.03; 95% CI: 1.38-2.99) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR 0.61; 95% CI: 0.47-0.79). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. Limitations Small sample size with low number of composite outcome events. Conclusion Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

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Section: Discussionmentioning

confidence: 79%

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

Menez

Moledina

Thiessen-Philbrook

et al. 2022

American Journal of Kidney Diseases

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“…The progression to CKD after CTS-AKI represents another area where biomarkers may add additional prognostic information. In the TRIBE-AKI cohort, epidermal growth factor (EGF) and monocyte chemoattractant protein-1 (MCP-1) were strongly associated with the risk of progression to CKD [103].…”

Section: Discussionmentioning

confidence: 99%

CSA-AKI: Incidence, Epidemiology, Clinical Outcomes, and Economic Impact

Schurle

Koyner

2021

JCM

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Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication following cardiac surgery and reflects a complex biological combination of patient pathology, perioperative stress, and medical management. Current diagnostic criteria, though increasingly standardized, are predicated on loss of renal function (as measured by functional biomarkers of the kidney). The addition of new diagnostic injury biomarkers to clinical practice has shown promise in identifying patients at risk of renal injury earlier in their course. The accurate and timely identification of a high-risk population may allow for bundled interventions to prevent the development of CSA-AKI, but further validation of these interventions is necessary. Once the diagnosis of CSA-AKI is established, evidence-based treatment is limited to supportive care. The cost of CSA-AKI is difficult to accurately estimate, given the diverse ways in which it impacts patient outcomes, from ICU length of stay to post-hospital rehabilitation to progression to CKD and ESRD. However, with the global rise in cardiac surgery volume, these costs are large and growing.

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“…The data analysis had no covariates with missing data. In addition, five imputed datasets with chained equations were created using R-package mice ( 16 ). Our multiple imputation of the dataset was mainly based on the following principles: (1) there were no missing data for the primary outcome; (2) replacement of categorical variables was not advisable, as the plausibility is still debated; (3) 5% missingness is suggested as a maximum upper threshold below which multiple imputation provides benefit.…”

Section: Methodsmentioning

confidence: 99%

Admission Lysophosphatidic Acid Is Related to Impaired Kidney Function in Acute Aortic Dissection: 2-Year Retrospective Follow-Up Study

Pan

Yang

Ding

et al. 2022

Front. Cardiovasc. Med.

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BackgroundDelayed treatment of acute aortic dissection (AAD)-related acute kidney injury (AKI) significantly increases the burden of chronic kidney disease (CKD) and mortality. Lysophosphatidic acid (LPA) is a shared mediator of kidney disease and AAD. Here, we evaluated the relationship between LPA and kidney injury in AAD patients.MethodsWe measured the plasma concentration of LPA in a cohort of 80 patients with AAD. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Logistic regression were used to evaluate the effect and interaction of LPA on AKI. Additive generalized model and penalized spline method were used to describe the non-linear association. Multivariable analyses with the Cox proportional-hazards model were used for subgroup analysis and interaction in LPA and subsequent CKD.ResultsThe participant’s average age was 54.27 ± 11.00 years, 68.75% of them were males, and the incidence of AKI was 43.75%. Patients with AKI had higher levels of LPA on admission, and the more significant the increase, the higher the risk of AKI. There was a non-linear positive correlation between admission LPA and AKI, and the premeditated inflection point was 346.33 (μg/dL) through two-piecewise linear regression and recursive algorithm. Subgroup analysis identified a stronger association between admission LPA and AKI in the elder, female and medically treated patients. The incidence of CKD was 22.67% in the 2-year follow-up. Patients with subsequent CKD had higher LPA levels on admission in the follow-up cohort, and a similar interaction trend was also observed through Cox proportional—hazards model.ConclusionAdmission LPA levels show a non-linear positive correlation with AKI and increase the risk of subsequent CKD, which is more pronounced in elderly, female, and medically treated patients.

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Urinary EGF and MCP-1 and risk of CKD after cardiac surgery

Abstract: and is co-inventor "Biomarkers and methods for progression prediction for chronic kidney disease"patent. All other authors declare that no conflicts of interest exist.

Cited by 28 publications

References 65 publications

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

CSA-AKI: Incidence, Epidemiology, Clinical Outcomes, and Economic Impact

Admission Lysophosphatidic Acid Is Related to Impaired Kidney Function in Acute Aortic Dissection: 2-Year Retrospective Follow-Up Study

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