Incidence of Acute Kidney Injury After Administration of Iodine Contrast Media in Patients With Reduced Renal Function (COINCIDES)

Cohort Study of Intravenous Contrast-media Influence on Decreased Renal Function

This study is examining if injection of iodine contrast media increases the risk of acute kidney injury in patients with severely reduced renal function. All patients who have a medical need for a computerized tomography, either with or without iodine contrast media, and has a renal function of less than estimated glomerular filtration rate (eGFR) 30 will be recruited. Blood and urine samples will be collected at baseline, three and 21 days after the computerized tomography. Additionally, we will examine if the decision to use iodine contrast media or not was easy or difficult if the use of iodine contrast media potentially changed the patient care and if it might have been lifesaving.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury Following Administration of Contrast Media
• Intervention / Treatment: Drug: Iodine-containing Contrast Media

Detailed Description

This is a single centre prospective cohort study performed at a tertiary level, university hospital in Sweden.

Background data included age, sex, height, and weight. Body surface area (BSA) is calculated with DuBois formula. Clinical history consists of chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus (DM), hypertension and liver failure. Details regarding the CT such as examined body part, clinical question on CT referral, if iodine contrast media (ICM) was used and, if so, which dose, type and concentration is going to be recorded.

Blood and urine samples will be collected three times prospectively and, if available, previously recorded plasma creatinine values will be recorded once as well. The retrospective value is recorded at least seven days before CT. The prospective values are going to be recorded within 24 hours before CT, 72 hours after CT and 21 days after CT. The following biomarkers are analysed in plasma: bicarbonate, creatinine, cystatin C and endostatin. The following biomarkers are analysed in urine: angiotensinogen (AGT), creatinine, cystatin C, endostatin, kidney injury molecule-1 (KIM-1), neutrophile gelatinase associated lipase (NGAL) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The revised Lund-Malmö formula is used to calculate eGFR based on creatinine. The Caucasian and Asian Paediatric and Adult subjects (CAPA) formula is used to calculate eGFR from Cystatin C.

Five yes or no-questions are going to be answered, two before the exam and three after. The questions answered before the exam will be answered by the radiologist who decided upon the exam protocol, and they are investigating if the decision to use ICM or not was easy to make. The questions after the exam are going to be answered by two senior radiologists independent of each other and they relate to if ICM helped in the discovery of clinically relevant information and if that information/condition was life-threatening. The third question will be answered by going through the patient's discharge summary and is looking at the main diagnosis and if that diagnosis would have been easier to discover with the use of ICM. Since no clear definition of life-threatening exists all diagnoses that were considered life-threatening will be stated in the manuscript. The data will be recorded in the electronic data capture REDCap.

Sample size has been calculated based on an incidence of 14%, a margin of error of 5% and a 95% confidence interval. If there will be to much missing data to run a complete observation analysis, and especially if it is unbalanced between ICM and no ICM an imputation will be performed.

Association will be evaluated with logistic regression. Test of difference among groups will be performed with chi-2 test for categorical variables and the Kruskal-Wallis test for continuous variables. If to many data points are missing and especially if it is unbalanced between groups imputation will be performed. Data will be presented as median and interquartile range or as frequency in percent where suitable. A significance level of 0.05 will be used.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Felix B Berglund, MD; Phone Number: +46703387606; Email: felix.berglund@uu.se

Study Locations

• Sweden
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Uppsala University
    • Contact: Per G Liss, PhD, MD; Phone Number: +46722223476; Email: per.liss@uu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients referred for a CT at Uppsala University Hospital which is a tertiary level hospital that also handles most emergency cases in Uppsala county, Sweden.

Description

Inclusion Criteria:

• eGFR <30 mL/min/1.73m2, calculated with the revised Lund-Malmö formula and plasma creatinine.
• Medical need of either an ICM-enhanced or unenhanced CT

Exclusion Criteria:

• <18 years of age
• Ongoing renal replacement therapy
• Ongoing treatment with nephrotoxic drugs. Drugs classified as nephrotoxic are acyclovir, aminoglycosides, ciclosporins, cisplatin, methotrexate, non-steroidal anti-inflammatory drugs (except low-dose aspirin) and vancomycin administered intravenously.
• Known allergy to ICM who and have not received prophylactic treatment (if patient belongs to ICM arm)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICM; Patients receiving ICM at CT	Drug: Iodine-containing Contrast Media; Patients will receive or not receive ICM depending on their medical need.
No ICM; Patients not receiving ICM at CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-contrast acute kidney injury (PC-AKI)	The primary outcome, PC-AKI, is defined and staged according to the creatinine-based criteria from Kidney Disease Improve Global Outcome (KDIGO) [5]. If any of these criteria are fulfilled 72 hours after ICM administration the patient had PC-AKI. The urine output criterion was not used in this study. PC-AKI should be read as post-CT AKI in patients not receiving ICM.	This outcome is measured 72 hours after CT.
Incidence of long-term decline in renal function	Any remaining increase in creatinine compared to baseline.	This outcome is measured 21 days after CT.
Incidence of long-term decline in renal function	Any remaining increase in cystatin C compared to baseline.	This outcome is measured 21 days after CT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of mortality	Mortality will be recorded during the follow-up period.	21 days
Incidence of need for renal replacement therapy	A need for any form of renal replacement during the follow-up period.	21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of elevated plasma bicarbonate	Elevation of bicarbonate in plasma compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated plasma endostatin compared to baseline	Elevation of endostatin in plasma compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine endostatin	Elevation of endostatin in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine creatinine	Elevation of creatinine in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine cystatine C	Elevation of cystatine C in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine KIM-1	Elevation of KIM-1 in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine NGAL	Elevation of NGAL in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.
Incidence of elevated urine TIMP-2	Elevation of TIMP-2 in urine compared with baseline value.	Data will be recorded at 72 hours and 21 days.

Collaborators and Investigators

• Sponsor: Uppsala University

Publications and helpful links

General Publications

• McDonald JS, McDonald RJ, Carter RE, Katzberg RW, Kallmes DF, Williamson EE. Risk of intravenous contrast material-mediated acute kidney injury: a propensity score-matched study stratified by baseline-estimated glomerular filtration rate. Radiology. 2014 Apr;271(1):65-73. doi: 10.1148/radiol.13130775. Epub 2014 Jan 16.
• Du BOIS D, Du BOIS EF. CLINICAL CALORIMETRY: TENTH PAPER A FORMULA TO ESTIMATE THE APPROXIMATE SURFACE AREA IF HEIGHT AND WEIGHT BE KNOWN. Archives of Internal Medicine. 1916;XVII(6_2):863-71.
• Bjork J, Grubb A, Sterner G, Nyman U. Revised equations for estimating glomerular filtration rate based on the Lund-Malmo Study cohort. Scand J Clin Lab Invest. 2011 May;71(3):232-9. doi: 10.3109/00365513.2011.557086. Epub 2011 Mar 10.
• Grubb A, Horio M, Hansson LO, Bjork J, Nyman U, Flodin M, Larsson A, Bokenkamp A, Yasuda Y, Blufpand H, Lindstrom V, Zegers I, Althaus H, Blirup-Jensen S, Itoh Y, Sjostrom P, Nordin G, Christensson A, Klima H, Sunde K, Hjort-Christensen P, Armbruster D, Ferrero C. Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. Clin Chem. 2014 Jul;60(7):974-86. doi: 10.1373/clinchem.2013.220707. Epub 2014 May 14.
• KDIGO. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International, Supplements. 2012;2(1).

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: acute kidney injury; cohort study; contrast media; tomography, x-ray computed; incidence study
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury
• Other Study ID Numbers: COINCIDES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The datasets generated and/or analysed during the current study are not publicly available due national and European Union regulations regarding patient related data but are available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No