Cardiac arrest (CA) remains a major cause of mortality and morbidity despite advances in resuscitation care. Patients who survive the initial event frequently develop post–cardiac arrest syndrome with varying degrees of multiorgan dysfunction. Among these complications, acute kidney injury (AKI) is common and is associated with prolonged ICU stay, higher mortality, and poorer neurological recovery. [1,2]

The mechanisms leading to AKI after cardiac arrest are complex. During cardiac arrest, reduced systemic perfusion causes renal ischemia. Following return of spontaneous circulation (ROSC), reperfusion injury further contributes to oxidative stress, endothelial dysfunction, and inflammatory activation. Persistent hypotension and hemodynamic instability may additionally worsen renal injury. [3] Because renal dysfunction can develop early after resuscitation, identifying high-risk patients at admission is clinically important.

Serum lactate is widely used as a marker of tissue hypoxia and impaired perfusion. Elevated lactate levels after cardiac arrest have been linked to adverse outcomes and greater severity of systemic ischemia. [4] Serum creatinine remains the standard laboratory marker for assessment of renal function; however, creatinine elevation may occur several hours after the onset of kidney injury, limiting its usefulness for early prediction of AKI.

The lactate–creatinine ratio (LCR) combines markers of systemic hypoperfusion and renal function into a single parameter. Because both measurements are routinely available in critically ill patients, LCR may serve as a practical bedside tool for early risk assessment. Previous studies evaluating the role of LCR in post–cardiac arrest AKI are limited. [5,6] The present study was conducted to evaluate the usefulness of admission LCR as a predictor of AKI in patients resuscitated after cardiac arrest.

The prospective observational study was conducted in the Tertiary care hospital's Intensive Care Unit (ICU) from January 2025 to December 2025 for a period of 12 months. Consecutive eligible patients were enrolled. Included were adult patients who were admitted to the ICU after successfully resuscitated from a cardiac arrest with Return of Spontaneous Circulation (ROSC). Cardiac arrests occurring in either a hospital or outside of the hospital were included in this study, as long as patients were admitted to the hospital within 6 hours of successful resuscitation from an arrest.

Exclusion criteria included known chronic kidney disease, patients receiving maintenance dialysis, known severe liver disease prior to arrest, patients who died within 24 hours were excluded because adequate follow-up for AKI assessment was not possible, patients who did not have complete laboratory data to establish a baseline creatinine and lactate prior to admission. Patients with incomplete laboratory data were excluded from analysis. There were approximately 80-120 patients included in the study, based on feasibility and expected case load over the study period. Approval for the study was obtained from the institutional ethics committee, and measures were taken to protect the confidentiality of all study participants throughout the study. Potential confounders including duration of CPR, hypotension, and comorbidities were recorded.

Baseline demographic information (age and sex) was collected, along with clinical data including the cause(s) of cardiac arrest; time CPR was being performed; and co-morbid diseases. Blood samples collected at the time of ICU admission for diagnostic evaluation included measurement of lactate (mmol/L) and creatinine (mg/dL) using standard laboratory techniques. The lactate-to-creatinine ratio (LCR) was calculated by dividing the lactate concentration by the creatinine concentration. Patients were subsequently followed, 48-72 hours after admission, for development of AKI during that time period. AKI was defined as an increase in creatinine of ≥0.3 mg/dL within 48 hours or a≥ 1.5-fold increase from baseline creatinine, per the KDIGO definition of acute kidney injury. The primary outcome of this study was to determine an association between LCR at the time of admission to the ICU and the development of AKI related to an arrest. Ethical approval for the study was obtained from the Institutional Ethics Committee of Great Eastern Medical School and Hospital prior to commencement of the study with Letter No. 54a/IEC/GEMS&H/IEC/2025 dated 24/06/2025. Written informed consent was obtained from the patient’s legally authorized representative whenever applicable. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Statistical Analysis:

Data entry and storage were performed using Microsoft Excel. Statistical analysis was carried out using IBM SPSS Statistics version 24.0. Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as frequency and percentage. Patients were divided into AKI and non-AKI groups based on the development of acute kidney injury within 48–72 hours after admission. Continuous variables were compared using the independent-samples t-test after assessment of normality. Categorical variables were analyzed using the Chi-square test or Fisher’s exact test where appropriate.

The association between admission lactate–creatinine ratio (LCR) and development of AKI was evaluated. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of LCR for AKI. The area under the curve (AUC) was calculated to determine discriminative ability. The optimal cutoff value was selected based on the best combination of sensitivity and specificity. A p-value <0.05 was considered statistically significant. Results were presented using tables and figures where appropriate.

A

A total of 100 patients with return of spontaneous circulation (ROSC) after cardiac arrest were included in the study. The mean age of the study population was 58.4 ± 12.6 years, with most patients belonging to the middle-aged and elderly groups. Males accounted for 65% of the cohort. (Table 1) Patients were divided according to the development of acute kidney injury (AKI) within 48–72 hours after admission. AKI occurred in 38 patients, while 62 patients did not develop AKI during the observation period. Overall, AKI was observed in 38% of the study population, indicating a substantial burden of renal dysfunction after cardiac arrest. Baseline clinical characteristics, including cause of cardiac arrest, duration of cardiopulmonary resuscitation (CPR), and associated comorbidities, were comparable between the two groups. However, patients who developed AKI experienced longer periods of hypotension during the post-resuscitation phase compared with the non-AKI group. The patient selection process is summarized in Figure 1. (Figure 1)

Admission laboratory parameters were compared between patients who developed acute kidney injury (AKI) and those who did not. Patients in the AKI group had significantly higher serum lactate levels than the non-AKI group (6.8 ± 2.1 mmol/L vs 4.2 ± 1.5 mmol/L, p<0.01), indicating more severe systemic hypoperfusion after cardiac arrest. Higher admission creatinine levels were also observed in patients who developed AKI (1.6 ± 0.4 mg/dL vs 1.1 ± 0.3 mg/dL, p<0.05). (Table 2) The lactate–creatinine ratio (LCR) showed a marked difference between the two groups. Mean LCR values were significantly higher in patients who developed AKI compared with those who did not (4.25 ± 1.3 vs 2.85 ± 0.9, p<0.001). (Figure 2)

Receiver operating characteristic (ROC) analysis demonstrated good predictive performance of LCR for AKI, with an area under the curve (AUC) of 0.82. (Table 3) An LCR cutoff value >3.5 predicted AKI with 78% sensitivity and 75% specificity. (Figure 3) Longer duration of cardiopulmonary resuscitation (CPR) and elevated lactate levels were also associated with AKI development. Patients requiring prolonged resuscitation were more likely to develop renal dysfunction during the post–cardiac arrest period. (Figure 4) Overall, these findings suggest that admission LCR may be a useful and readily available marker for early identification of patients at increased risk of AKI after cardiac arrest.

Table 1: Baseline Demographic and Clinical Characteristics

This table presents the baseline demographic and clinical profile of the study population. Age and gender distribution were comparable between the AKI and non-AKI groups, with no statistically significant difference (p > 0.05). However, patients who developed AKI had a significantly longer duration of cardiopulmonary resuscitation (CPR) and a higher frequency of hemodynamic instability, suggesting a greater degree of systemic insult in this group.

Table 2: Comparison of Laboratory Parameters at Admission

This table compares admission laboratory parameters between AKI and non-AKI groups. Patients who developed AKI had significantly higher serum lactate and creatinine levels. Notably, the lactate–creatinine ratio (LCR) was markedly elevated in the AKI group, demonstrating the strongest statistical association (p < 0.001), indicating its potential as a predictive biomarker.

Table 3: ROC Analysis of LCR for Predicting AKI

This table summarizes the diagnostic performance of LCR in predicting AKI using ROC curve analysis. The LCR showed good discriminative ability with an AUC of 0.82. A cutoff value of >3.5 provided a sensitivity of 78% and specificity of 75%, supporting its utility as an effective tool for early risk stratification.

The present study evaluated the role of admission lactate–creatinine ratio (LCR) in predicting acute kidney injury (AKI) after cardiac arrest. AKI developed in 38% of patients within 48–72 hours after return of spontaneous circulation (ROSC), highlighting the frequency of renal complications in this population. [7,8] Patients who developed AKI had significantly higher serum lactate, serum creatinine, and LCR values at admission compared with those who did not develop AKI. Among these variables, LCR showed the strongest association with AKI development. [9,10]

Renal injury after cardiac arrest is multifactorial. During cardiac arrest, reduced systemic perfusion leads to renal ischemia and tubular injury. Reperfusion following ROSC can further aggravate cellular damage through oxidative stress, endothelial dysfunction, and inflammatory activation. [11-14] Persistent hypotension and impaired microcirculation may also worsen renal perfusion during the post-resuscitation period. Because these processes begin early, identifying patients at increased risk of AKI soon after admission remains clinically important. Serum lactate is commonly used as a marker of tissue hypoperfusion and metabolic stress. In the current study, patients who developed AKI had higher lactate levels at admission, consistent with previous reports linking hyperlactatemia to organ dysfunction and poor outcomes in critically ill patients. [15,16] Elevated creatinine levels were also observed in the AKI group, suggesting early renal impairment even before fulfillment of KDIGO criteria.

Although serum creatinine remains the standard marker for renal function assessment, it has important limitations. Creatinine elevation often occurs several hours after kidney injury and may be influenced by muscle mass, hydration status, and age. [17-20] Relying solely on creatinine may delay recognition of early AKI in post–cardiac arrest patients. The lactate–creatinine ratio combines markers of systemic hypoperfusion and renal dysfunction into a single parameter. In the present study, mean LCR values were significantly higher in patients who developed AKI than in those who did not (4.25±1.3 vs 2.85±0.9; p<0.001). These findings suggest that LCR may help identify renal injury earlier than conventional markers alone. Similar observations have been reported in recent studies evaluating combined biomarkers in critically ill patients. [21,22]. Receiver operating characteristic analysis demonstrated good predictive performance of LCR, with an AUC of 0.82. An LCR cutoff value >3.5 provided acceptable sensitivity and specificity for identifying patients at risk of AKI. From a clinical perspective, this may help guide closer renal monitoring, optimization of hemodynamic status, and avoidance of nephrotoxic exposure in high-risk patients. [3,22] Our findings are consistent with previous studies showing an association between elevated lactate levels and adverse outcomes after cardiac arrest. Earlier investigations have also demonstrated the prognostic value of creatinine in AKI and critical illness. However, literature evaluating the combined use of lactate and creatinine as an integrated ratio remains limited. [19-23] The present study adds further evidence supporting the potential role of LCR as a practical bedside biomarker in post–cardiac arrest care. In addition to elevated LCR, prolonged cardiopulmonary resuscitation (CPR) and higher lactate levels were associated with AKI development in our cohort. Longer CPR duration likely reflects prolonged global ischemia and greater organ injury burden. [24] Severe metabolic derangement and persistent hypoperfusion may also contribute to worsening renal dysfunction. [25] One advantage of LCR is its practicality. Both lactate and creatinine are routinely measured in critically ill patients, making the ratio easy to calculate without additional cost. This may be particularly useful in resource-limited settings where access to novel biomarkers is restricted. [26]

Several limitations should be acknowledged. First, this was a single-center study with a relatively small sample size, which may limit generalizability. Second, long-term renal and neurological outcomes were not evaluated. Third, factors such as vasopressor requirements, fluid balance, and nephrotoxic drug exposure were not analyzed in detail. [27] Larger multicenter studies are needed to validate these findings and determine whether serial LCR measurements improve predictive accuracy. Comparative studies with newer biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C may further clarify the role of LCR in early AKI prediction. [28-31].

The present study demonstrated a significant association between admission lactate–creatinine ratio and development of acute kidney injury after cardiac arrest. Patients who developed AKI had substantially higher LCR values at ICU admission, and the ratio showed good predictive performance on ROC analysis. Because lactate and creatinine are routinely available laboratory parameters, LCR may serve as a practical bedside tool for early identification of high-risk patients. Larger multicenter studies are needed to validate these findings and determine the role of serial LCR measurements in post-cardiac arrest care.

1. Roberts BW, Kilgannon JH, Chansky ME, Mittal N, Wooden J, Parrillo JE, et al. Multiple organ dysfunction after return of spontaneous circulation in postcardiac arrest syndrome. Crit Care Med 2013;41(6):1492-1501.
2. Tujjar O, Mineo G, Dell’Anna A, Poyatos-Robles B, Donadello K, Scolletta S, et al. Acute kidney injury after cardiac arrest. Crit Care 2015;19:169.
3. Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013;17(1):204.
4. Donnino MW, Andersen LW, Giberson T, Gaieski DF, Abella BS, Peberdy MA, et al. Initial lactate and lactate change in post-cardiac arrest: a multicenter validation study. Crit Care Med 2014;42(8):1804-1811.
5. Deulkar P, Singam A, Mudiganti VNKS, Jain A. Lactate monitoring in intensive care: a comprehensive review of its utility and interpretation. Cureus 2024;16(8).
6. Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 2013;88(10):1127-1140.
7. Aslan M, Yılmaz R, Birtane D, Çukurova Z. Causes and clinical outcomes of acute kidney injury after cardiac arrest: a retrospective cohort study. Medicina (Kaunas) 2025;61(2):338.
8. Zhang S, Luo M, Lu Z, Shi Q. Lactate and lactylation in sepsis-associated acute kidney injury: clinical evidence from the MIMIC-IV database and mechanistic insights. Front Med (Lausanne) 2025;12:1708145.
9. Cai Q, Ye X, He Y, Liu Q, Huang J, Chen G, et al. Association between the lactate-to-creatinine ratio and hospital mortality in pediatric sepsis: a cohort study. Pediatr Res 2026;89(1):1-8.
10. Makris K, Spanou L. Acute kidney injury: definition, pathophysiology and clinical phenotypes. Clin Biochem Rev 2016;37(2):85-98.
11. Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron 2002;90(2):133-138.
12. Kushimoto S, Akaishi S, Sato T, Nomura R, Fujita M, Kudo D, et al. Lactate, a useful marker for disease mortality and severity but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients. Acute Med Surg 2016;3(4):293-297.
13. Wang X, Mu J, Ma K, Ma Y. Challenges of serum creatinine level in GFR assessment and drug dosing decisions in kidney injury. Adv Pharm Bull 2024;14(4):745-758.
14. Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereira AB, Kirsztajn GM, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol 2008;3(2):348-354.
15. Waikar SS, Bonventre JV. Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol 2009;20(3):672-679.
16. Murty MSN, Sharma UK, Pandey VB, Kankare SB. Serum cystatin C as a marker of renal function in detection of early acute kidney injury. Indian J Nephrol 2013;23(3):180-183.
17. Bhosale SJ, Kulkarni AP. Biomarkers in acute kidney injury. Indian J Crit Care Med 2020;24(Suppl 3).
18. Nahm FS. Receiver operating characteristic curve: overview and practical use for clinicians. Korean J Anesthesiol 2022;75(1):25-36.
19. Lazzarin T, Tonon CR, Martins D, da Rosa AV, da Silva BC, Schmitz F, et al. Post-cardiac arrest syndrome: mechanisms, management, and future perspectives. J Clin Med 2022;12(1):259.
20. Heilmann E, Gregoriano C, Schuetz P. Biomarkers of infection: are they useful in the ICU? Semin Respir Crit Care Med 2019;40(4):465-475.
21. Serdar CC, Cihan M, Yücel D, Serdar MA. Sample size, power and effect size revisited: simplified and practical approaches in clinical studies. Biochem Med (Zagreb) 2021;31(1):010502.
22. Naqvi R, Hossain N, Butt S, Anwar F, Hussain M, Ahmad S, et al. Efficacy of multiple biomarkers: NGAL, KIM-1, cystatin C and IL-18 in predicting pregnancy-related acute kidney injury. Pak J Med Sci 2023;39(1):34-40.
23. Sandroni C, Nolan JP, Andersen LW, Böttiger BW, Cariou A, Cronberg T, et al. ERC-ESICM guidelines on temperature control after cardiac arrest in adults. Intensive Care Med 2022;48(3):261-269.
24. Ostermann M, Liu K. Pathophysiology of AKI. Best Pract Res Clin Anaesthesiol 2017;31(3):305-314.
25. Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol 2018;14(10):607-625.
26. Wiersema R, Jukarainen S, Eck RJ, Kaufmann T, Koeze J, Keus F, et al. Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-I study. Crit Care 2020;24(1):164.
27. Honore PM, Redant S, Attou R, Gallerani A, De Bels D. Biomarkers for early diagnosis of AKI in the ICU: ready for prime time use at the bedside? Ann Intensive Care 2021;11(1):113.
28. Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019;394(10212):1949-1964.
29. Kokkoris S, Pipili C, Grapsa E. Renal dysfunction in critically ill patients with sepsis. World J Crit Care Med 2019;8(6):135-143.
30. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets. Signal Transduct Target Ther 2024;9(1):34.
31. Centers for Disease Control and Prevention. Chikungunya virus: Clinical evaluation and disease. [Online] Available from: https://www.cdc.gov/chikungunya/hc/clinicalevaluation.html [Accessed on August 1, 2025].