Circulating tumor necrosis factor α receptors predict the outcomes of human IgA nephropathy

A prospective cohort study

Yun Jung Oh, Jung Nam An, Clara Tammy Kim, Seung Hee Yang, Hajeong Lee, Dong Ki Kim, Kwon Wook Joo, Jin Ho Paik, Shin-Wook Kang, Jung Tak Park, Chun Soo Lim, Yon Su Kim, Jung Pyo Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0132826
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - 2015 Jul 15

Fingerprint

tumor necrosis factors
Tumor Necrosis Factor Receptors
kidney diseases
cohort studies
Immunoglobulin A
Cohort Studies
Prospective Studies
receptors
Receptors, Tumor Necrosis Factor, Type II
Receptors, Tumor Necrosis Factor, Type I
Kidney
kidneys
Biopsy
biopsy
Hazards
endpoints
Histology
glomerular filtration rate
Biomarkers
renal function

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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. / Circulating tumor necrosis factor α receptors predict the outcomes of human IgA nephropathy : A prospective cohort study. In: PLoS One. 2015 ; Vol. 10, No. 7.
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abstract = "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.",
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Oh, YJ, An, JN, Kim, CT, Yang, SH, Lee, H, Kim, DK, Joo, KW, Paik, JH, Kang, S-W, Park, JT, Lim, CS, Kim, YS & Lee, JP 2015, 'Circulating tumor necrosis factor α receptors predict the outcomes of human IgA nephropathy: A prospective cohort study', PLoS One, vol. 10, no. 7, e0132826. https://doi.org/10.1371/journal.pone.0132826

Circulating tumor necrosis factor α receptors predict the outcomes of human IgA nephropathy : A prospective cohort study. / 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.

In: PLoS One, Vol. 10, No. 7, e0132826, 15.07.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Circulating tumor necrosis factor α receptors predict the outcomes of human IgA nephropathy

T2 - A prospective cohort study

AU - Oh, Yun Jung

AU - An, Jung Nam

AU - Kim, Clara Tammy

AU - Yang, Seung Hee

AU - Lee, Hajeong

AU - Kim, Dong Ki

AU - Joo, Kwon Wook

AU - Paik, Jin Ho

AU - Kang, Shin-Wook

AU - Park, Jung Tak

AU - Lim, Chun Soo

AU - Kim, Yon Su

AU - Lee, Jung Pyo

PY - 2015/7/15

Y1 - 2015/7/15

N2 - 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.

AB - 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.

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