New Indices to Detect Acute Kidney Injury in Coronary Artery Disease Patients

ABSTRACT IMAGE

INTRODUCTION

Contrast-associated acute kidney injury (CA-AKI) is attributed to the contrast agents administrated at the time of diagnostic or therapeutic coronary interventions.^[1] It is one of the leading causes of acute kidney injury. It contributes to prolonged duration of hospital stay, the requirement of hemodialysis, and increased in-hospital mortality and morbidity. Hence, early identification and development of predictive scores can aid in reducing post-procedure renal injury.^[2,3] Patients with ischemic heart disease and liver insufficiency are at risk of perioperative complications.^[4] Among themselves, patients undergoing percutaneous coronary intervention (PCI) are at risk of AKI and associated with a poor prognosis. Hence, pre-operative liver function assessment and risk stratification are important to prevent such procedural complications.^[5,6]

MATERIALS AND METHODS

It is a prospective study conducted at Nizam’s Institute of Medical Sciences, Hyderabad. The study aimed to assess the prognostic capacity of the De-Ritis ratio in anticipating the development of CA-AKI who underwent PCI. One hundred and fifty cases were enrolled who underwent elective PCI between June 2022 and August 2022. The study included patients with coronary artery disease who underwent elective PCI and had aspartate transaminase (AST) and alanine aminotransferase (ALT) values below 200 mg/dL and patients unwilling to give consent were excluded from study. The following patients were excluded: Patients who had end-stage renal disease or dialysis-dependent, received contrast 1 week prior or 8 h post-procedure, had a history of concurrent administration of any nephrotoxic drug 1 week before or 48 h after the procedure, or those who succumbed within 24 h of admission.

Contrast-induced AKI: This is the acute reduction in renal function, described as an elevation in serum creatinine of ≥0.5 mg/dL or ≥25% compared to baseline. It usually develops 24–72 h post-administration of an IV contrast agent in the absence of other identifiable causes. Data were collected including demographic, clinical, laboratory, and angiographic details. Biochemical parameters such as lipid profile, fasting blood sugars, alanine aminotransferase, aspartate aminotransferase, bilirubin, international normalized ratio, uric acid, and the cue were collected on admission. Serum creatinine measurements were taken on admission and continued for 2 consecutive days. A team of expert interventional cardiologists conducted the procedures. The investigator played no part in determining the approach and technique used for revascularization. PCI was done using IOHEXOL which is a non-ionic contrast of osmolality 780 mOsm/kg. The X-ray contrast medium used is a monomeric tri-iodinated, water-soluble substance with a concentration of 350 mg iodine per milliliter (mL). Each injection typically has a volume ranging from 4 mL to 8 mL. Subsequently, patients received intravenous normal saline at a rate of 1 mL/kg/h for 12 h during the periprocedural period. However, in the case of heart failure patients, the rate was adjusted to 0.5 mL/kg/h.

RESULTS

A total of 150 patients were enrolled in the study. Table 1 displays the baseline characteristics of the study population. The average age of the patients was 51.9 ± 9.2 years, with 105 (70%) being male and 45 (30%) being female. Based on the De-Ritis ratio, the patients were categorized into two groups: those with a ratio ≤1.30 (low) and those with a ratio >1.30 (high). Among the study population, 13 (8.6%) patients had a high ratio, while 137 (91.3%) had a low ratio.

The high-ratio group exhibited elevated AST, TGs, and LDL-cholesterol in contrast to the low-ratio group.

Out of total 150 patients, 12 (8%) developed CA-AKI. Within this group, 10 (76.9%) patients were part of the high De-Ritis ratio group [Table 2], indicating a significantly associated among the De-Ritis ratio and the CA-AKI occurrence (P ≤ 0.001), which was significantly higher than the association observed with ALT (P = 0.164) and AST (P = 0.362) alone [Table 3]. The sensitivity and specificity are 83.33% and specificity 97.83%, respectively. The positive predictive value and negative predictive value are 76.92% and 98.54%, respectively. The accuracy of the test is 96.67%

CA-AKI developed in 12 (8%) of the patients. The optimal cutoff value for the De-Ritis ratio in predicting CA-AKI was determined to be 1.3, demonstrating a sensitivity of 83.3% and a specificity of 97.83%.

DISCUSSION

In this research, we investigated the correlation between De-Ritis ratio, and CA-AKI in elective PCI patients [Figure 1 and Table 4]. Our findings revealed that patients who had more De-Ritis ratio had a significantly increased occurrence of CA-AKI. Patients with liver insufficiency who underwent PCI experienced a higher incidence of AKI and were frequently linked to unfavorable clinical outcomes.^[7] In their study, Alqahtani et al. reported that patients who had liver cirrhosis and underwent PCI were at a high risk of developing AKI and had a higher in-hospital death rate compared to without cirrhosis.^[8,9] Similarly, a larger countrywide database analysis demonstrated a greater incidence rate of intestinal bleeding, AKI, 90-day death rate, and 90-day readmission rate.^[10] Hence, conducting a prior assessment of liver function plays a critical role in reducing procedural complications.

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Figure 1:

Correlation between contrast-associated acute kidney injury and De-Ritis ratio. AST: Aspartate transaminase, ALT: Alanine aminotransferase.

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AST and ALT are used as markers for liver injury. When combined as the De-Ritis ratio, these levels can indicate liver dysfunction.^[11] In addition, the ratio has been confirmed to be associated with adverse outcomes in patients with myocardial infarction,^[12] diabetes,^[13] and cardiac arrest.^[14,15]

In a retrospective study involving 422 patients who undergone hepatectomy, it was observed that a De-Ritis ratio is ≥1.29 served as a standalone risk element for AKI, even after accounting for other potential influencing factors.^[16,17] In another longitudinal retrospective study, 6264 patients who undergone surgery related to cardiovascular demonstrated that a high De-Ritis ratio was associated with a significant correlation between mortality and AKI. Likewise, in a previous study, an elevated De-Ritis ratio was identified as a prognosticator for AKI requiring dialysis and early to mid-term mortality after the implantation of a left ventricular assist device.The ratio can be served as a convenient and quick surrogate marker for assessing pre-procedure liver function, and it proves to be valuable in predicting the occurrence of CA-AKI after elective PCI. In cases where the De-Ritis ratio exceeds 1.30, it is crucial to identify the underlying cause of liver dysfunction and initiate appropriate treatment.^[18,19]

The exact reason behind the connection between an elevated ratio and CA-AKI remains unknown. As previously cited, elevated levels of the ratio are linked to impaired hepatic function.^[11] Moreover, hepatic impairment can result in an imbalance between vasodilatory and vasoconstricting factors, leading to splanchnic and systemic vasodilation and renal vasoconstriction. Ultimately, these mechanisms contribute to renal dysfunction and the development of CA-AKI. Indeed, ALT is exclusively found in the cytoplasm of liver cells, whereas AST is present in both the mitochondria and cytoplasm. It has been postulated that a high ratio might be attributed to mitochondrial impairment, which, in turn, may be a result of oxidative stress.^[13] Indeed, oxidative stress and inflammation has been shown to be associated with CA-AKI. Therefore, it is sensible to propose that an elevated De-Ritis ratio is correlated with a higher risk of developing CA-AKI.^[20] Therefore, a high De-Ritis ratio could be indicative of impaired renal function, which, in turn, may be associated with an increased risk of CA-AKI.

CONCLUSION

The findings of this study demonstrate that the De-Ritis ratio acts as an independent risk factor for the development of CA-AKI in patients undergoing elective PCI. These results provide evidence supporting the potential utility of the DeRitis ratio as a convenient and quick liver function evaluation tool for risk classification. Implementing measures based on the De-Ritis ratio before the procedure could help clinicians mitigate the post-procedural risk of CA-AKI.