Recontrast and Renal Outcomes in Patients With Pre-Existing Renal Dysfunction

Methodology

Study design, recruitment and study location: This is a prospective observational cohort study. Patients were consecutively recruited from the intensive care units of Cairo University hospitals between March 2024 and November 2025 and were followed after discharge through outpatient clinics, in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The study protocol approved by the Faculty of Medicine, Cairo University Research Ethics Committee, on 13-1-2024, with the approval number N-20-2024.

Exposure groups: Participants were categorized into two groups according to the number of intravascular contrast administrations received during the study period into two groups.

• Group I: patients who underwent a single contrast exposure with impaired kidney function.
• Group II: Patients who received two contrast administrations with impaired kidney function.

Data collection: For the enrolled patients, baseline variables were extracted from the hospital database. Before any data handling or analysis, all records were comprehensively anonymized to ensure confidentiality. Collected data included demographic characteristics (age, sex, and body mass index), clinical parameters (blood pressure, primary diagnosis, cause of ICU admission, CKD stage, smoking status), comorbid conditions (diabetes mellitus, hypertension, heart failure/cardiovascular disease, liver disease, previous stroke and dyslipidemia) and medication history (angiotensin converting enzyme inhibitors/angiotensin receptor blockers, sodium-glucose cotransporter 2 inhibitors, and statins).

Additional parameters recorded included number of contrast enhanced procedures performed, time between first and second contrast exposure (in case of repeated exposures) and total volume and cumulative volume of contrast administered (in case of repeated exposures). Furthermore, the risk of contrast-induced nephropathy (CIN) and the estimated probability of requiring dialysis were calculated using the Mehran score.

Laboratory investigations at baseline: serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, blood urea, serum potassium, glycated hemoglobin (HbA1c), total cholesterol, and triglycerides were recorded for all patients. All blood samples were analyzed using the same standardized enzymatic assay (Cobas; Roche chemistry analyzer).

Frequency of renal function monitoring during the study:

Creatinine was measured at baseline 48 hours before each exposure, day 7, and 1, 3, and 6 months after the final exposure, while eGFR was assessed at baseline and at 3, and 6 months. In addition, urine output (ml/hour) was recorded 48 hours after each contrast administration.

CKD stratification: CKD was graded according to the KDOQI (Kidney Disease Outcomes Quality Initiative). The estimated glomerular filtration rate (eGFR) was calculated with the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula: [eGFR = 142×min (Scr/κ,1) α×max (Scr/κ,1) -1.200 × 0.9938 Age× Sex Factor] .

Variables: Scr = serum creatinine (mg/dL), κ (kappa) = 0.7 for females, 0.9 for males, α (alpha) = - 0.241 for females, - 0.302 for males, Sex Factor = 1.012 for females, 1.000 for male, Age = age in years, min (Scr/κ, 1) = the smaller of Scr/κ or 1, max (Scr/κ, 1) = the larger of Scr/κ or 1.

Contrast data: For all investigations, all patients received (Omnipaque), a low-osmolar, nonionic, iodinated contrast agent. According to local guidelines, Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and nonsteroidal anti-inflammatory drugs were withheld on the morning of the contrast examination. Dehydration was avoided by discontinuation of diuretic medication on the day before and on the days of the study, and good oral hydration was ensured; in a few patients, this was supplemented by administration of intravenous fluids (Isotonic saline (0.9% NaCl) at 1 mL/kg/hr for 6 hours pre and post contrast).

All standard precautions were observed, including administration of pre-medication (Dexamethasone, antihistamine and anti-emetic) as per local protocol of our hospital.

In this study, the second contrast exposure was not contingent upon documented recovery from the initial insult but rather occurred as clinically indicated within the same admission or ongoing course of care. Patients could therefore undergo re-exposure even in the absence of full renal recovery, reflecting real-world ICU practice where urgent diagnostic or therapeutic needs often necessitate repeated imaging irrespective of prior injury resolution.

Bias Minimization: Several measures were taken to minimize potential sources of bias. Selection bias was addressed through consecutive enrolment of eligible patients meeting prespecified inclusion and exclusion criteria, rather than convenience sampling, and reporting followed STROBE guidelines for observational cohort studies. Information and measurement bias were reduced by using standardized, prespecified outcome definitions (KDIGO criteria for CA-AKI and KDOQI staging for CKD), a single validated formula (2021 CKD-EPI) for eGFR calculation, and a single enzymatic assay platform (Cobas; Roche) for all serum creatinine measurements, ensuring consistency of laboratory results across both groups and over time. Contrast administration and periprocedural prophylaxis were delivered according to a fixed institutional protocol for all patients, limiting variability that could differentially affect renal outcomes between exposure groups.

Data were extracted from the hospital database using a structured, prespecified case-record form and anonymized prior to analysis to reduce recall and observer bias. To minimize confounding, baseline demographic, clinical, and laboratory characteristics were compared between groups and found to be similar, and multivariable logistic regression was used to adjust for clinically relevant covariates when identifying predictors of CA-AKI and CKD progression. Nonetheless, as exposure group allocation was determined by clinical indication rather than randomization, residual confounding by indication cannot be fully excluded and is addressed further in the Discussion.

Sample size: The study is an exploratory one to assess predictors of CKD progression following contrast exposure and evaluate if this differs after single vs. multiple exposures to contrast.

Statistical analysis: Descriptive statistics were done and categorical variables were presented as frequency and percentage. Numerical variables were tested for normality, and normally distributed data were presented as mean and standard deviation, while non-normally distributed ones were presented as median and interquartile range. Numerical data were tested for normality using Shapiro Wilk test. Comparison between the two study groups was performed using the Chi-square test or Fischer's exact test for the categorical variables as appropriate. For the comparison of the numerical variables, the 2 groups Student's t test was used for normally distributed data, while the Wilcoxon rank-sum test was used for non-normally distributed data. For the comparison of the change in relevant variables in two different time points the Wilcoxon rank matched pairs test was used. Comparative analyses were performed both across the entire studied groups and within each chronic kidney disease (CKD) stage, contrasting outcomes between patients with repeated versus single contrast administration. Logistic regression analysis was performed to explore predictors of CA-AKI and CKD progression, with adjustment for clinically relevant covariates. The dependent variables used include CKD progression at different time points, CA-AKI. STATA 15.1 was used for the analysis, Copyright 1985-2017 STATA Crop LLC, College Station, Texas 77845 USA. P values < 0.05 were deemed significant.

Inclusion criteria

• Adults aged 18 years or older with baseline eGFR <90 mL/min/1.73 m² who underwent at least one intravascular iodinated contrast study

Exclusion criteria

• Kidney transplant within the preceding 6 months
• Ongoing renal replacement therapy
• Hemodynamic shock
• Severe sepsis
• Recent nephrotoxic drug exposure
• Incomplete laboratory data
• Prior contrast allergy.