Discovery and Validation of Biomarkers for CSA-AKI Risk Prediction

China National Center for Cardiovascular Diseases1,500 enrolled

Overview

This study aims to discover and validate new biomarkers for predicting CSA-AKI before cardiovascular surgery. Nested case-control studies embedded in prospective cohorts. Adult patients scheduled for cardiovascular surgery were continuously included. Blood/urine/stool samples and clinical data before and after contrast agent exposure and before and after cardiovascular surgery were collected, and the occurrence, progression and outcome of CSA-AKI events were dynamically monitored. Based on the exposure to contrast agents and the occurrence of CSA-AKI, two case-controls were constructed in the prospective cohort. In the construction of two case-controls, biomarkers were identified and validated by using multi-omics analysis techniques and machine learning techniques, etc.

Study Type

OBSERVATIONAL

Enrollment

1,500

Conditions

CSA-AKI Acute Kidney Injury Cardiovascular Surgery Biomarkers

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 1\. Age no less than 18 years old; * 2\. Scheduled cardiovascular surgery is proposed; * 3\. Pre-angiography and preoperative serum creatinine \<354 μ mol/L; * 4\. Informed consent. Exclusion Criteria: * 1\. Women who have a pregnancy plan within one year, are pregnant, or are breastfeeding; * 2\. Patients who have severe side effects such as allergies to iodine contrast agents; * 3\. Patients with hyperthyroidism; * 4\. Those who had AKI before the contrast agent or within 2 weeks before the operation, or whose AKI has not been relieved after the operation; * 5\. Patients undergoing kidney transplantation, peritoneal dialysis, or hemodialysis treatment; * 6\. Patients with malignant tumors or those with an expected lifespan of less than 12 months; * 7\. Angiography or preoperative acute heart failure; * 8\. Patients who have a history of massive hemorrhage in the past 30 days or have contraindications to anticoagulant therapy.

Outcomes

Primary Outcomes

The occurrence of CSA-AKI

CSA-AKI is defined as: serum creatinine (SCr) within 48 hours after cardiovascular surgery increases by ≥26.5 µmol/L compared with the baseline, or SCr increases by ≥ 50% times the baseline value within 7 days after surgery, or urine output is less than 0.5 mL/kg/h and persists for more than 6 hours.

Time frame: The assessment will be conducted from the end of the surgery until the 7th day after the operation.

Secondary Outcomes

The occurrence of severe CSA-AKI(i.e. AKI stage 2 or 3)

Acute kidney injury at stage 2 or stage 3 as defined by the KDIGO 2012 guidelines.AKI stage 2 is defined as:meet any of the following conditions: 1. Serum creatinine index: Serum creatinine rises to 2.0-2.9 times the baseline value. 2. Urine volume index: Urine volume remains consistently below 0.5 mL/kg/h for more than 12 hours. AKI stage 3 is defined as: meeting any of the following conditions: 1. Serum creatinine index: Serum creatinine increases to 3.0 times or more of the baseline value; Or the serum creatinine level rises to ≥ 4.0 mg/dL (≥ 353.6 μmol/L); Or start renal replacement therapy (such as hemodialysis, peritoneal dialysis). 2. Urine volume index: Urine volume remains consistently below 0.3 mL/kg/h for more than 24 hours; Or anuria (urine output \< 100 mL/ day) persists for 12 hours or more.

Time frame: The assessment will be conducted from the end of the surgery until the 7th day after the operation.

CSA-AKI as defined by the AKIN standard

CSA-AKI as defined by AKIN: that is, the increase of serum creatinine within 48 hours is \>26.5umol/L or \> 50% of the baseline.

Time frame: From the preoperative period to 48 hours after the operation

The occurrence of persistent acute kidney injury

Persistent acute kidney injury is defined as acute kidney injury that persists for more than 48 hours after its initial diagnosis, based on serum creatinine and/or urine output according to KDIGO criteria.

Time frame: From the end of surgery through postoperative day 7

Renal replacement therapy or in-hospital death

Receiving any form of renal replacement therapy (such as continuous renal replacement therapy, intermittent hemodialysis, etc.) or any in-hospital death caused by any reason.

Time frame: From the end of cardiac surgery until the date of first occurrence of renal replacement therapy or in-hospital death, whichever came first, assessed up to 1 year after cardiac surgery.

The length of stay in the ICU and the total length of stay

Record the total number of days the patient was admitted to the ICU and the total number of days of this hospitalization

Time frame: The length of stay in the ICU:From ICU admission until ICU discharge, up to 3 months after surgery The total length of stay:From hospital admission until hospital discharge, up to 1 year after surgery

New-onset acute kidney disease (AKD）

According to the KDIGO guidelines, a state where renal function remains persistently abnormal (serum creatinine or urine output does not return to baseline) for more than 7 days but less than 90 days after the occurrence of acute kidney injury

Time frame: Postoperative day 8 to 90 days

Major adverse cardiovascular events (MACE) within 1 year after surgery

The composite endpoints that occurred within 1 year after surgery included cardiovascular death, myocardial infarction, heart failure and stroke.

Time frame: From the end of surgery to 1 year after surgery

Change in Estimated Glomerular Filtration Rate (eGFR)

The change in eGFR will be calculated as the difference between eGFR at 1 year after the index cardiovascular surgery and baseline eGFR, expressed in mL/min/1.73 m².

Time frame: From baseline to 1 year after cardiac surgery

New CKD or progression of existing CKD

Incidence of newly diagnosed chronic kidney disease or progression of pre-existing chronic kidney disease, based on KDIGO CKD criteria.

Time frame: Within 1 year after cardiac surgery

MAKE

Composite endpoints that occurred within one year after surgery, including: a \> 50% decrease in eGFR from baseline, entry into end-stage renal disease (initiating maintenance dialysis or receiving kidney transplantation), or death related to kidney disease.

Time frame: Follow-up assessment was conducted from the end of the surgery until one year after the operation.

MACE

The composite endpoints that occurred within one year after the operation, including cardiovascular death, myocardial infarction, heart failure and stroke.