Diagnostic value of inflammatory and renal tubular biomarkers in patients with cardiorenal syndrome: a cross-sectional study
- Authors: Almammadov F.C.1, Jafarova G.A.1
-
Affiliations:
- Azerbaijan Medical University
- Issue: Vol 107, No 2 (2026)
- Pages: 200-209
- Section: Theoretical and clinical medicine
- Submitted: 16.11.2025
- Accepted: 26.01.2026
- Published: 28.03.2026
- URL: https://kazanmedjournal.ru/kazanmedj/article/view/696334
- DOI: https://doi.org/10.17816/KMJ696334
- EDN: https://elibrary.ru/MUQFMC
- ID: 696334
Cite item
Abstract
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.
Full Text
About the authors
Fazil Ch. Almammadov
Azerbaijan Medical University
Author for correspondence.
Email: xeyalcafarov4@gmail.com
ORCID iD: 0009-0004-4041-6905
MD, Cand. Sci. (Medicine), Depart. of Family Medicine
Azerbaijan, Narimanov, Baku, AZ2712Gulnara A. Jafarova
Azerbaijan Medical University
Email: gulcicekceferova@gmail.com
ORCID iD: 0009-0009-5177-1634
Cand. Sci. (Biology), senior research associate, Depart. of Biological Chemistry
Azerbaijan, BakuReferences
- Reznik EV, Nikitin IG. Cardiorenal syndrome in patients with chronic heart failure as a stage of the cardiorenal continuum (part I): definition, classification, pathogenesis, diagnosis, epidemiology. The Russian Archives of Internal Medicine. 2019;9(1):5–22. doi: 10.20514/2226-6704-2019-9-1-5-22 EDN: WEOQBU
- Tsibul’kin NA, Novozhilova AA, Khakimova DM. Cardiorenal syndrome: pathogenesis, clinical picture. Kazan medical journal. 2016;97(2):274–278. doi: 10.17750/KMJ2016-274 EDN: VRCQPX
- Medvedeva EA, Shilyaeva NV, Iskhakov EN, Schukin YuV. Cardiorenal syndrome in chronic heart failure: pathogenesis, diagnostics, prognosis and opportunities for treatment. Russian Journal of Cardiology. 2017;(1):136–141. doi: 10.15829/1560-4071-2017-1-136-141 EDN: XRMCRD
- Mitsas AC, Elzawawi M, Mavrogeni S, et al. Heart failure and cardiorenal syndrome: a narrative review on pathophysiology, diagnostic and therapeutic regimens-from a cardiologist's view. J Clin Med. 2022;11(23):7041. doi: 10.3390/jcm11237041 EDN: RTXGFQ
- Gallo G, Lanza O, Savoia C. New insight in cardiorenal syndrome: from biomarkers to therapy. Int J Mol Sci. 2023;24(6):5089. doi: 10.3390/ijms24065089 EDN: HWUXJC
- Ferdinand KC, Norris KC, Rodbard HW, Trujillo JM. Humanistic and economic burden of patients with cardiorenal metabolic conditions: a systematic review. Diabetes Ther. 2023;14(12):1–18. doi: 10.1007/s13300-023-01464-8 EDN: BXTHTO
- Bouquegneau A, Krzesinski JM, Delanaye P, Cavalier E. Biomarkers and physiopathology in the cardiorenal syndrome. Clin Chim Acta. 2015;443:100–107. doi: 10.1016/j.cca.2014.10.041
- Goffredo G, Barone R, Di Terlizzi V, et al. Biomarkers in Cardiorenal Syndrome. J Clin Med. 2021;10(15):3433. doi: 10.3390/jcm10153433 EDN: DCBBYX
- Rahimova RR, Dashdamirova GS, Shahverdiyeva IJ, Karimova IA. Studying the activity of matrix metalloproteinases and antibodies to DNA in patients with autoimmune thyroiditis. Kazan medical journal. 2023;104(6):851–858. doi: 10.17816/KMJ624114 EDN: TWDYCU
- Benoit SW, Ciccia EA, Devarajan P. Cystatin C as a biomarker of chronic kidney disease: latest developments. Expert Rev Mol Diagn. 2020;20(10):1019–1026. doi: 10.1080/14737159.2020.1768849 EDN: HVFTZA
- Dundar A, Irmak H, Ayhanci T, Cetik Yildiz S. Evaluation of serum levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as potential biomarkers of renal tubular damage in brucellosis patients. Int J Gen Med. 2025;18:5039–5046. doi: 10.2147/IJGM.S544766 EDN: SNZGCN
- Xu Y, Xie Y, Shao X, et al. L-FABP: a novel biomarker of kidney disease. Clin Chim Acta. 2015;445:85–90. doi: 10.1016/j.cca.2015.03.017
- Delalić Đ, Brežni T, Prkačin I. Diagnostic value and utility of commonly used biomarkers of cardiac and renal function in cardiorenal syndromes: a narrative review. Biochem Med (Zagreb). 2023;33(3):030502.
- Kumar A, Chidambaram V, Geetha HS, et al. Renal Biomarkers in Heart Failure: Systematic Review and Meta-Analysis. JACC Adv. 2024;3(2):100765. doi: 10.1016/j.jacadv.2023.100765 EDN: CFOVQQ
- Xu C, Lin S, Mao L, Li Z. Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury requiring renal replacement therapy: a systematic review and meta-analysis. Front Med. 2022;9:859318. doi: 10.3389/fmed.2022.859318
- Romejko K, Markowska M, Niemczyk S. The review of current knowledge on neutrophil gelatinase-associated lipocalin (NGAL). Int J Mol Sci. 2023;24(13):10470. doi: 10.3390/ijms241310470 EDN: LJRZBY
- Sunayama T, Yatsu S, Matsue Y, et al. Urinary liver-type fatty acid-binding protein as a prognostic marker in patients with acute heart failure. ESC Heart Fail. 2022;9(1):442–449. doi: 10.1002/ehf2.13730 EDN: COLCPW
- Sircuta AF, Grosu ID, Schiller A, et al. The relationship between circulating kidney injury molecule-1 and cardiovascular morbidity and mortality in hemodialysis patients. Biomedicines. 2024;12(8):1903. doi: 10.3390/biomedicines12081903 EDN: QCDITM
- Marchiori GN, Defagó MD, Baraquet ML, et al. Interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein for optimal immunometabolic profiling of the lifestyle-related cardiorenal risk. Diagnosis. 2024;11(1):82–90. doi: 10.1515/dx-2023-0159 EDN: VMOUPU
- Dri E, Lampas E, Lazaros G, et al. Inflammatory mediators of endothelial dysfunction. Life. 2023;13(6):1420. doi: 10.3390/life13061420 EDN: URKLUZ
- Vasquez F, Tiscornia C, Lorca-Ponce E, et al. Cardiorenal syndrome: molecular pathways linking cardiovascular dysfunction and chronic kidney disease progression. Int J Mol Sci. 2025;26(15):7440. doi: 10.3390/ijms26157440 EDN: YEDNTC
- Virzì GM, Breglia A, Brocca A, et al. Levels of proinflammatory cytokines, oxidative stress, and tissue damage markers in patients with acute heart failure with and without cardiorenal syndrome type 1. Cardiorenal Med. 2018;8(4):321–331. doi: 10.1159/000492602
- Katkenov N, Mukhatayev Z, Kozhakhmetov S, et al. Systematic review on the role of IL-6 and IL-1β in cardiovascular diseases. J Cardiovasc Dev Dis. 2024;11(7):206. doi: 10.3390/jcdd11070206 EDN: YREJZD
- Papamichail A, Kourek C, Briasoulis A, et al. Targeting key inflammatory mechanisms underlying heart failure: a comprehensive review. Int J Mol Sci. 2023;25(1):510. doi: 10.3390/ijms25010510 EDN: TTAWPR
- Gupta L, Thomas J, Ravichandran R, et al. Inflammation in cardiovascular disease: a comprehensive review of biomarkers and therapeutic targets. Cureus. 2023;15(9):e45483. doi: 10.7759/cureus.45483 EDN: QZYWAF
- Mitsis A, Sokratous S, Karmioti G, et al. The Role of C-Reactive Protein in Acute Myocardial Infarction: Unmasking Diagnostic, Prognostic, and Therapeutic Insights. J Clin Med. 2025;14:4795. doi: 10.3390/jcm14134795 EDN: NYMFVK
- Gupta A, Sontakke T, Acharya S, Kumar S. A comprehensive review of biomarkers for chronic kidney disease in older individuals: current perspectives and future directions. Cureus. 2024;16(9):e70262. doi: 10.7759/cureus.70262 EDN: MXONYZ
- Mitsides N, Mitra V, Saha A, et al. Urinary liver-type fatty acid binding protein, a biomarker for disease progression, dialysis and overall mortality in chronic kidney disease. J Pers Med. 2023;13(10):1481. doi: 10.3390/jpm13101481 EDN: QZLAZS
- Satta E, Strollo F, Borgia L, et al. Urinary L-FABP: a novel biomarker for evaluating diabetic nephropathy onset and progression-a narrative review. Diabetes Ther. 2025;16:1107–1124. doi: 10.1007/s13300-025-01731-w EDN: JMIDHG
- Dutta A, Saha S, Bahl A, et al. A comprehensive review of acute cardiorenal syndrome: need for novel biomarkers. Front Pharmacol. 2023;14:1152055. doi: 10.3389/fphar.2023.1152055 EDN: ILZNDI
- Aletras G, Bachlitzanaki M, Stratinaki M, et al. Integrating novel biomarkers into clinical practice: a practical framework for diagnosis and management of cardiorenal syndrome. Life. 2025;15(10):1540. doi: 10.3390/life15101540 EDN: RUXIWD



