Contrast induced-acute kidney injury : new insights into risk prediction of contrast induced-acute kidney injury and peri-procedural nephroprotective therapies

As an interventional cardiologist, my PhD research was motivated by the clinical problem of contrast-induced acute kidney injury (CI-AKI) that is a potential complication arising from the numerous coronary angiography and percutaneous coronary interventions that I do. Although most contrast media are considered safe, at-risk individuals can develop CI-AKI. CI-AKI is not an uncommon complication after coronary angiographic procedures with a reported incidence of 1-2% in the general population and could be as high as 50% in high-risk patient subgroups. My PhD, which is divided into 2 parts, is to provide new insights into risk prediction of CI-AKI and peri-procedural nephroprotective therapies. Specifically, my PhD addressed research questions related to firstly, the risk prediction of CI-AKI in patients undergoing percutaneous intervention and examine if patients could be identified for periprocedural intervention and secondly to test the potential benefits of a peri-procedural therapeutic intervention to prevent CI-AKI in patients undergoing percutaneous interventions. CI-AKI risk prediction scores have been developed but these often involved the use of contrast volume in score calculations that limits their application in identifying patients who might benefit from peri-procedural strategies that protect the kidney. In the first part of my PhD thesis, I evaluated 2 recently proposed pre-procedural risk scores that do not include procedural variables including the contrast volume: Modified Mehran Score and the score developed by Liu and colleagues (Liu Prediction Score) to determine their ability to identify at risk patients undergoing chronic total occlusion percutaneous intervention (CTO PCI). I prospectively enrolled 329 consecutive and eligible patients (mean age 60.9±8.6 years, 64.1% Males; baseline eGFR 76.1±22.5 ml/min, serum creatinine 1.0±0.2 mg/dL) undergoing CTO PCI at our institution from December 1st 2017 to October 28 2020. All patients provided written informed consent to participate in this clinical study. The Modified Pre-procedural Mehran Score utilized the variables in Mehran score except the contrast volume. The Liu Prediction Score utilized four key risk factors (age ≥75 years, LVEF < 40%, serum albumin < 30 g/L and Serum Creatinine (SCr) >1.5 mg/dL) for predicting CI-AKI. The performance of the Modified Mehran Score and Liu Prediction Score were compared with the performance of the original Mehran score using area under the receiver operator characteristic curve (AUROC). Sensitivity and specificity were also compared for different cut-off values. 29 (8.8%) cases developed CI-AKI, defined as a 25% increase or an absolute increase in SCr ≥0.5 mg/dL over baseline within 48-72 h after contrast medium exposure. The removal of contrast volume from Mehran score resulted in no loss of discrimination (AUROC 0.9591 vs 0.9514 for the original Mehran and the modified Mehran respectively, P=NS). Full Mehran score had an optimal cut-point of 11 that resulted in a 0.90 accuracy of predicting CI-AKI with a sensitivity of 93.1% and a specificity of 90.0%. Modified Mehran score had an optimal cut-point of 7 that resulted in a 0.85 accuracy of predicting CI-AKI with a sensitivity of 96.6% and a specificity of 83.3%. With an optimal cut point of 5.5, the Liu score that was determined in 208 patients that had available serum albumin resulted in a 0.90 accuracy of predicting CI-AKI with a sensitivity of 100.0% and a specificity of 89.3%. A recent meta-analysis of high-volume forced diuresis with matched hydration using the RenalGuard medical device system revealed a significant reduction in the risk of CI-AKI, major adverse cardiac event rate, and the need for renal replacement therapy. However, the RenalGuard device is not widely available and affordable especially in low-middle income countries such as Kurdistan. In the second part of my PhD thesis, I designed and conducted the CINEMA trial (ISRCTN Registry Number: 72194653) to evaluate the potential benefits of a non-automated matched hydration and forced diuresis (MHFD) protocol compared to current hydration protocol in the prevention of contrast induced AKI. A total of 1,205 consecutive patients with chronic kidney disease (CKD) undergoing coronary procedures were randomized to either non-automated MHFD (MHFD group, n = 799) or standard intravenous isotonic saline hydration (control group; n= 406). The MHFD group received 250 ml normal saline (NS) bolus over 30 minutes before the coronary procedure followed by an intravenous bolus (0.5 mg/kg) of furosemide. Hydration infusion rate was manually adjusted to replace the patient's urine output. When urine output rate reached >300 ml/h, patients underwent coronary procedure. Matched fluid replacement was maintained during the procedure and for 4 h post-treatment. CI-AKI was defined conventionally as ≥25% or ≥0.5 mg/dl rise in serum creatinine over baseline. In the MHFD group, less patients developed CI-AKI (MHFD vs control: CI-AKI, 64 (8.01%) patients vs 57 (14.04%), p < 0.001). Incidence of cumulative in-hospital clinical complications was similar in both MHFD-treated patients and controls. In conclusion, in the CINEMA trial, I have shown that a non- automated MHFD protocol is effective and safe method for the prevention of CI-AKI in patients with CKD. I have also shown that both a modified pre-procedural Mehran score as well as the Liu Risk Score have potential use to identify patients undergoing CTO PCI for peri-procedural nephroprotective therapies such as with the matched hydration protocol as in the CINEMA trial. Taken together, my research findings have shown the utility of pre-procedural risk prediction scores to identify at risk individuals who could be targeted for a non-automated MHFD to prevent CI-AKI.