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BACKGROUND: Early and accurate assessment of inflammatory and renal tubular biomarkers is clinically relevant to diagnose and evaluate progression of type 2 cardiorenal syndrome; however, their combined diagnostic value remains insufficiently studied. AIM: This study aimed to evaluate the diagnostic value of inflammatory and renal tubular biomarkers in patients with type 2 cardiorenal syndrome. METHODS: The study was conducted at the 1st Clinical Medical Center in Baku in 2020–2024 and included 200 patients with type 2 cardiorenal syndrome and 51 apparently healthy individuals. Patients were stratified by functional class of chronic heart failure based on the New York Heart Association classification and the stage of chronic kidney disease: group 1 (n = 74) with functional class I–II and stage I–II, respectively; group 2 (n = 9) with functional class I–II and stage III–IV, respectively; group 3 (n = 73) with functional class III–IV and stage I–II, respectively; group 4 (n = 44) with functional class III–IV and stage III–IV, respectively. The levels of cystatin C, lipocalin, liver-type fatty acid–binding protein, kidney injury molecule 1 (KIM-1) in blood and urine, interleukin-6, interleukin-18, and tumor necrosis factor-alpha were determined. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and correlations were evaluated using the Spearman correlation method. RESULTS: In all groups, a pronounced increase in the studied markers compared with the control group was observed (p 0.001), with progressive elevation in line with disease severity. The levels of cystatin C, lipocalin, liver-type fatty acid–binding protein, and KIM-1 increased 2.9-, 2.1-, 3.1-, and 2.3/2.0-fold, respectively, in group 1 (p 0.001); 4.2-, 2.9-, 5.6-, and 5.1/2.7-fold in group 2 (p 0.001); 3.4-, 2.4-, 4.2-, and 2.6/2.3-fold in group 3 (p 0.001); and 6.4-, 3.4-, 7.2-, and 5.8/3.4-fold in group 4 (p 0.001). The levels of interleukin-6, interleukin-18, and tumor necrosis factor-alpha also increased: 3.9- and 2.8-fold and by 89.0%, respectively, in group 1; 5.2-, 2.9-, and 2.5-fold in group 2; 4.4-, 4.0-, and 2.1-fold in group 3; and 6.4-, 5.2-, and 3.1-fold in group 4 (p 0.001). Marker concentrations correlated with the stage of chronic kidney disease (ρ = 0.676–0.861; p 0.001) and the functional class of chronic heart failure (ρ = 0.301–0.514; p 0.001), whereas lipocalin and KIM-1 correlated with interleukin-6 and interleukin-18 levels (ρ = 0.894–0.920; p 0.001). The highest diagnostic value was identified for liver-type fatty acid–binding protein (AUC: 0.819; 95% CI: 0.761–0.876; p 0.001), lipocalin (AUC: 0.768; 95% CI: 0.702–0.834; p 0.001), and KIM-1 (AUC: 0.745; 95% CI: 0.678–0.813; p 0.001). CONCLUSION: Inflammatory and renal tubular biomarkers have high diagnostic value and are consistent with the progression of cardiorenal dysfunction in type 2 cardiorenal syndrome.