Molecular Insights into Gene Expression Changes in Apoptosis Immune Response and Cellular Regulation Pathways in Chronic Kidney Disease Patients

Abstract

Chronic kidney disease (CKD) is a complex, multifactorial disease characterized by the overlapping pathways of apoptosis, immune regulation, and fibrosis, which play a pivotal role in disease progression. However, the molecular integration of these pathways remains incompletely understood, particularly regarding their combined impact on the deterioration of renal function. The study included 60 participants: 30 patients with CKD and 30 healthy individuals as a control group. Hematological and biochemical parameters, including hemoglobin, hematocrit, urea, creatinine, and glucose, were assessed. Gene expression of CASP8, CASP9, PDCD1, CTLA4, and TGFB3 was analyzed using RT-qPCR, with the 2−ΔΔCt method employed to calculate relative variability. Statistical analyses were performed using comparison tests and correlation analysis. Compared healthy individuals with CKD patients showed significant differences in biochemical, and molecular parameters. A significant decrease in hemoglobin levels (9.37 ± 0.50 vs. 14.18 ± 0.64 g/dL) and hematocrit (28.63 ± 1.40 vs. 40.69 ± 1.91), compared to a significant increase in urea (124.38 ± 17.39 vs. 29.64 ± 2.25 mg/dL) and creatinine (8.16 ± 0.63 vs. 0.75 ± 0.03 mg/dL) (p < 0.001). At the molecular level, significant increases in the gene expression of CASP8 (46.09 ± 6.70 folds) and CASP9 (13.59 ± 1.51 folds) were observed, along with elevated levels of PDCD1 (25.66 ± 4.19), CTLA4 (34.69 ± 8.43), and TGFB3 (15.29 ± 2.83). These findings suggest a complex regulatory network involving apoptosis activation, immunosuppression, and fibrosis in patients with CKD. These results highlight an integrated molecular axis that may represent a promising target for future therapeutic interventions and provide a foundation for a deeper understanding of the pathogenic mechanisms underlying disease progression.