Circulating Tumor Necrosis Factor α Receptors Predict the Outcomes of Human IgA Nephropathy: A Prospective Cohort Study

• Published in: PloS one Vol. 10; no. 7; p. e0132826
• Main Authors: Oh, Yun Jung, An, Jung Nam, Kim, Clara Tammy, Yang, Seung Hee, Lee, Hajeong, Kim, Dong Ki, Joo, Kwon Wook, Paik, Jin Ho, Kang, Shin-Wook, Park, Jung Tak, Lim, Chun Soo, Kim, Yon Su, Lee, Jung Pyo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.07.2015; Public Library of Science (PLoS)
• Subjects: Adult; Atrophy; Bioindicators; Biomarkers; Biomarkers - blood; Biopsy; Cohort analysis; Cytokines; Diabetes mellitus; Disease Progression; Epidermal growth factor receptors; Female; Fibrosis; Glomerular filtration rate; Glomerulonephritis, IGA - blood; Glomerulonephritis, IGA - mortality; Glomerulonephritis, IGA - therapy; Growth factors; Hazards; Health hazards; Histology; Humans; IgA nephropathy; Immunoglobulin A; Internal medicine; Kidney diseases; Kidney transplantation; Lesions; Male; Medicine; Microscopy; Middle Aged; Multivariate Analysis; Necrosis; Pathology; Patients; Physicians; Proportional Hazards Models; Prospective Studies; Proteinuria; Quartiles; Receptors; Receptors, Tumor Necrosis Factor, Type I - blood; Receptors, Tumor Necrosis Factor, Type II - blood; Renal function; Statistical models; Subgroups; TNF inhibitors; Transplants & implants; Treatment Outcome; Tumor necrosis factor receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0132826

The circulating tumor necrosis factor receptors (TNFRs) could predict the long-term renal outcome in diabetes, but the role of circulating TNFRs in other chronic kidney disease has not been reported. Here, we investigated the correlation between circulating TNFRs and renal histologic findings on kidney biopsy in IgA nephropathy (IgAN) and assessed the notion that the circulating TNFRs could predict the clinical outcome. 347 consecutive biopsy-proven IgAN patients between 2006 and 2012 were prospectively enrolled. Concentrations of circulating TNFRs were measured using serum samples stored at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; ≥ 30% decline compared to baseline). Mean eGFR decreased and proteinuria worsened proportionally as circulating TNFR1 and TNFR2 increased (P < 0.001). Tubulointerstitial lesions such as interstitial fibrosis and tubular atrophy were significantly more severe as concentrations of circulating TNFRs increased, regardless of eGFR levels. The risks of reaching the primary endpoint were significantly higher in the highest quartile of TNFRs compared with other quartiles by the Cox proportional hazards model (TNFR1; hazard ratio 7.48, P < 0.001, TNFR2; hazard ratio 2.51, P = 0.021). In stratified analysis according to initial renal function classified by the eGFR levels of 60 mL/min/1.73 m2, TNFR1 and TNFR2 were significant predictors of renal progression in both subgroups. In conclusion, circulating TNFRs reflect the histology and clinical severity of IgAN. Moreover, elevated concentrations of circulating TNFRs at baseline are early biomarkers for subsequent renal progression in IgAN patients.