IDENTIFICATION OF MOLECULAR MARKERS AND MICRORNAS ASSOCIATED WITH DISEASE SEVERITY IN CHRONIC KIDNEY DISEASE PATIENTS WITH LIVER DYSFUNCTION

Abstract

Background: Chronic kidney disease (CKD) is a progressive and irreversible disorder frequently associated with liver dysfunction, resulting in increased morbidity and poor clinical outcomes. Conventional renal and hepatic biomarkers may not adequately reflect the molecular mechanisms underlying disease progression. Molecular biomarkers and microRNAs (miRNAs) have emerged as promising tools for evaluating renal injury, fibrosis, inflammation, and disease severity in CKD patients with concomitant liver dysfunction.

Methods: This experimental cross-sectional study was conducted in the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Institute, Kolhapur. Sixty adult CKD patients with liver dysfunction and twenty healthy controls were enrolled. Clinical, hematological, renal, and liver function parameters were assessed. Plasma levels of Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Matrix Metalloproteinase-9 (MMP-9) were measured. Expression of miR-21, miR-29, and miR-122 was quantified using quantitative real-time PCR. Biomarker levels were compared between groups and across CKD stages, and correlations with estimated glomerular filtration rate (eGFR), serum creatinine, blood urea, and liver function tests were analyzed.

Results: CKD patients with liver dysfunction demonstrated significantly elevated KIM-1 (417.27 vs. 209.08 pg/mL), NGAL (447.27 vs. 210.05 pg/mL), MMP-9 (2311.52 vs. 1632.56 pg/mL), and miR-21 expression (2.71 vs. 1.29-fold), while miR-29 expression was significantly reduced (0.38 vs. 1.09-fold) compared with controls (all p<0.001). These biomarkers exhibited progressive stage-wise alterations with advancing CKD severity. MiR-29 showed the strongest correlation with eGFR (r=+0.974, p<0.001) and serum creatinine (r=−0.916, p<0.001), followed by KIM-1, NGAL, MMP-9, and miR-21. MiR-122 demonstrated no significant differences between groups or correlations with renal or hepatic parameters. None of the evaluated biomarkers showed significant association with liver function tests.

Conclusion: KIM-1, NGAL, MMP-9, miR-21, and particularly miR-29 are strongly associated with CKD severity in patients with liver dysfunction. Among these, miR-29 emerged as the most sensitive molecular marker for disease staging and progression. These biomarkers may serve as valuable non-invasive tools for risk stratification, monitoring, and precision management of CKD patients with concomitant liver dysfunction.