ASSOCIATION OF CORRELATION BETWEEN TNF-Α GENE EXPRESSION WITH IL-18, SYNDECAN-1, NT-PROBNP AND HSCRP LEVELS IN PATIENTS WITH END-STAGE RENAL DISEASE UNDERGOING HEMODIALYSIS

Abstract

Background: End-stage renal disease (ESRD) is accompanied by uremia, chronic inflammation, endothelial injury and cardiovascular stress. Although hemodialysis effectively removes small water-soluble solutes, its immediate influence on inflammatory and endothelial biomarkers, and on the underlying transcriptional inflammatory program, is less predictable. This study evaluated serum interleukin-18 (IL-18), syndecan-1 (SDC-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP), together with urea, creatinine and peripheral blood tumor necrosis factor-alpha (TNF-α) gene expression, before and after hemodialysis, and compared both dialysis states with healthy controls. Methods: Thirty-four clinically stable adults receiving maintenance hemodialysis and 22 apparently healthy controls were studied. Blood was collected immediately before and after one dialysis session. Protein biomarkers were measured by sandwich ELISA and renal parameters by enzymatic colorimetric assays. TNF-α mRNA expression was quantified by real-time quantitative PCR (RT-qPCR) using GAPDH as the reference gene and an efficiency-corrected relative-quantification model, expressed as fold-change relative to the mean control value. Mann–Whitney U, Wilcoxon signed-rank, Spearman correlation and receiver-operating-characteristic (ROC) analyses were used. Results: Pre-HD patients had significantly higher IL-18, SDC-1, NT-proBNP, hsCRP, urea and creatinine than controls (all P≤0.001). After dialysis, all four protein biomarkers remained significantly higher than controls. Urea and creatinine fell markedly after treatment (both P<0.001), whereas IL 18, SDC-1 and hsCRP did not change significantly; NT-proBNP increased significantly (P=0.039). TNF-α gene expression was approximately two-fold higher in Pre-HD (mean 2.03±0.62-fold; median 1.95, IQR 1.61–2.34) and Post-HD patients (mean 2.07±0.60-fold; median 2.09, IQR 1.58–2.47) than in controls (mean 1.00±0.30 fold) (both P<0.001), with excellent discrimination from controls (AUC 0.96 and 0.95, respectively), but showed no significant paired change across the single dialysis session (P=0.723). Strong positive correlations were observed among several inflammatory, endothelial and cardiac markers. ROC analysis showed excellent discrimination for hsCRP and NT-proBNP. Conclusion: A single high-flux hemodialysis session produced effective small-solute clearance but did not normalize the protein or transcriptional inflammatory profile of ESRD. TNF-α mRNA was markedly upregulated in ESRD and remained elevated after treatment, mirroring the pattern seen for hsCRP, IL-18 and SDC-1. The findings support an integrated inflammatory endothelial, cardiovascular, and molecular phenotype in ESRD and suggest that multimarker assessment, extending from the circulating protein level to the gene-expression level, may provide more information than any single biomarker.