PARAMETER-KINETICS OF APOPTOSIS INHIBITOR OF MACROPHAGE (AIM) IN CONTRAST-ASSOCIATED ACUTE KIDNEY INJURY: A PILOT STUDY

Contrast-induced acute kidney injury (CA-AKI) is one of the major causes for AKI. To diagnose CA-AKI, we use serum creatinine (SCr), however, its slow kinetics makes it difficult to diagnose it in earlier stage. In contrast, serum kidney injury molecule-1 (KIM-1) is reported as one of the earlier biomarkers for CA-AKI. KIM-1 collaborates with apoptosis inhibitor of macrophage (AIM) to help recovering from AKI. Our study objective is to describe AIM kinetics in CA-AKI high-risk patients undergoing angiography (AG).

This study was conducted between September 2021 and April 2022 at a tertiary center in Japan. Patients who underwent clinically required coronary/lower limb AG and with eGFR lower than 60 mL/min/1.73m2 were eligible. We excluded patients under age 18; who had received renal replacement therapy; who had allergy to iodinated contrast media (CM); who had an emergency AG; and who had used CM within the past two weeks, to minimize the potential impact on AIM. All patients were given 0.9% normal saline from one day before until the end of the day of AG to prevent CA-AKI as per our center’s protocol. We used clinically required amount of nonionic low-osmotic/isosmotic iodinated CM for all participants. We collected serum/urine samples before (T0); immediately after (T1); 12–24 hours after (T2); 36–48 hours after (T3); and 7–14 days after (T4) the AG. CA-AKI biomarkers of SCr, cystatin C, urine neutrophil gelatinase-associated lipocalin (NGAL), serum KIM-1, as well as serum/urine immunoglobulin M-free AIM (fAIM) were measured by enzyme-linked immunosorbent assay. We defined CA-AKI as meeting any of the following criteria of: 1) an increase in SCr by ≥ 0.3 mg/dL within 48 hours after AG, or ≥ 1.5-fold increase from baseline within 7 days after AG; 2) serum cystatin C increase of 10% from baseline within 24h after AG; 3) urine NGAL ≥ 20 ng/mL, or increase of 50% from baseline within 24h after AG; 4) serum KIM-1 ≥ 0.425 ng/mL within 6h after AG. In analysis, we plotted each participant’s AIM overtime. Also, we described median (interquartile range) of AIM for T0-4, and compared them between patient with/without CA-AKI using Wilcoxon’s rank sum test. 

Twenty patients underwent AG, and we excluded 4 patients who met exclusion criteria; thus 16 patients were analyzed. The patients’ overall age was 71.5 (66.7–81) with baseline eGFR of 50.1 (45.1–55.6) mL/min/1.73m2; 12 (75%) were male, and 7 (43.8%) had diabetes. One patient (6.2%) was given isosmotic CM, others were given low-osmotic CM. CM was administered via radial artery, or femoral artery, with a dose of 75 (60–103) mL (1.31 [0.9–1.6] mL/kg). Six patients (37.5%) had undergone percutaneous intervention, and CA-AKI had experienced in three (18.8%) patients. Baseline serum/urine fAIM for non-CA-AKI group were 1.12 (1.02–1.48) μg/mL, and 0.31 (0.09–0.64) μg/gCr; and those for CA-AKI group were 1.42 (1.32–1.65), and 0.60 (0.51–2.33), respectively, and there was no difference between two groups. Serum/urine  fAIM values after AG for non-CA-AKI vs. CA-AKI groups were T1: 0.99 (0.69–1.40) vs. 1.55 (1.35–1.82), and 0.21 (0.07–0.26) vs. 0.98 (0.49–4.01); T2: 1.19 (0.77–1.59) vs. 1.62 (1.15–2.18), and 0.50 (0.00–0.95) vs. 3.29 (2.42–4.16, p = 0.079); T3 (data only available for non-CA-AKI group): 0.92 (0.88–1.18), and 0.05 (0.00–0.21); T4: 1.43 (1.07–1.50) vs. 1.27 (1.11–1.42), and 0.03 (0.00–0.59) vs. 0.18 (0.09–0.28), respectively (Figure 1 shows boxplots of T0–T4 urine fAIM between non-CA-AKI and CA-AKI group).

Urine fAIM for CA-AKI group might have higher trend towards T2 than non-CA-AKI group, however, a larger study is needed.