Association of Peritoneal Dialysis Effluent Interleukin-17 with Peritoneal Functional Decline and Clinical Significance: A Prospective Cohort Study

Lejia Song; Lu Li; Guang Chen; Qiufeng Wang; Qingqing Rao; Huaina Dou; Li Zhang; Pei Zhang

doi:10.71321/g94y8w65

Authors

Lejia Song The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Lu Li The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Guang Chen The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Qiufeng Wang The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Qingqing Rao The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Huaina Dou Anhui Medical University, Hefei, Anhui, China.
Li Zhang Anhui Medical University, Hefei, Anhui, China.
Pei Zhang The First Affiliated Hospital of Anhui Medical University

DOI:

https://doi.org/10.71321/g94y8w65

Keywords:

Peritoneal dialysis, Peritoneal fibrosis, Peritoneal function, Biomarker, IL-17

Abstract

Background: Long-term peritoneal dialysis (PD) frequently induces chronic peritoneal inflammation, fibrosis, and increased peritoneal solute transport rate (PSTR). This study assessed whether effluent interleukin-17 (IL-17) predicts increased PSTR and relates to peritoneal fibrosis.
Methods: This prospective cohort enrolled 130 PD patients, of whom 115 completed 1-year follow-up. Effluent IL-17, transforming growth factor-β (TGF-β), and fibronectin (FN) were measured by enzyme-linked immunosorbent assay (ELISA). Peritoneal function was assessed by dialysate-to-plasma creatinine ratio (D/P Cr) at baseline and 1 year. We used correlation analysis, multivariable regression, interaction analysis, and Receiver operating characteristic (ROC) analysis to evaluate the predictive value of effluent IL-17 for increased PSTR. A mouse peritoneal fibrosis model was used to evaluate local IL-17 expression by immunohistochemistry and real-time quantitative PCR (RT-qPCR).
Results: Effluent IL-17 was higher in patients with increased PSTR and correlated positively with TGF-β, FN, and ΔD/P Cr. Multivariable analysis showed that IL-17 independently predicted 1-year D/P Cr after adjustment for baseline D/P Cr and clinical covariates. PD vintage significantly modified the association between IL-17 and increased PSTR. Adding IL-17 to baseline D/P Cr and peritoneal creatinine clearance improved prediction of increased PSTR, with the AUC increasing from 0.705 to 0.789. Furthermore, immunohistochemical and qPCR results showed that IL-17 expression was elevated in fibrotic peritoneal tissues of PF mice compared with control mice.
Conclusion: Effluent IL-17 is associated with peritoneal fibrosis and longitudinal PSTR increase, supporting its potential as a noninvasive biomarker for early risk stratification in PD patients.

References

[1] Cho Y, Bello AK, Levin A, Lunney M, Osman MA, Ye F, et al. (2021). Peritoneal Dialysis Use and Practice Patterns: An International Survey Study. Am J Kidney Dis, 77(3), 315–325. https://doi.org/10.1053/j.ajkd.2020.05.032

[2] Suryantoro SD, Thaha M, Sutanto H, & Firdausa S. (2023). Current Insights into Cellular Determinants of Peritoneal Fibrosis in Peritoneal Dialysis: A Narrative Review. J Clin Med, 12(13). https://doi.org/10.3390/jcm12134401

[3] Teitelbaum I. (2021). Peritoneal Dialysis. N Engl J Med, 385(19), 1786–1795. https://doi.org/10.1056/NEJMra2100152

[4] Gu J, Bai E, Ge C, Winograd J, & Shah AD. (2023). Peritoneal equilibration testing: Your questions answered. Perit Dial Int, 43(5), 361–373. https://doi.org/10.1177/08968608221133629

[5] Brimble KS, Walker M, Margetts PJ, Kundhal KK, & Rabbat CG. (2006). Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis. J Am Soc Nephrol, 17(9), 2591–2598. https://doi.org/10.1681/asn.2006030194

[6] Mehrotra R, Ravel V, Streja E, Kuttykrishnan S, Adams SV, Katz R, et al. (2015). Peritoneal Equilibration Test and Patient Outcomes. Clin J Am Soc Nephrol, 10(11), 1990–2001. https://doi.org/10.2215/cjn.03470315

[7] Graterol Torres F, Molina M, Soler-Majoral J, Romero-González G, Rodríguez Chitiva N, Troya-Saborido M, et al. (2022). Evolving concepts on inflammatory biomarkers and malnutrition in chronic kidney disease. Nutrients, 14, 4297. https://doi.org/https://doi.org/10.3390/nu14204297

[8] Prasad N, Chaturvedi S, Singh H, Udumula MP, Rawat A, Jeyakumar M, et al. (2025). Peritoneal Dialysis -Associated Fibrosis: Emerging Mechanisms and Therapeutic Opportunities. Front Pharmacol, 16, 1635624. https://doi.org/10.3389/fphar.2025.1635624

[9] Iwakura Y, Ishigame H, Saijo S, & Nakae S. (2011). Functional specialization of interleukin-17 family members. Immunity, 34(2), 149–162. https://doi.org/10.1016/j.immuni.2011.02.012

[10] Marchant V, Tejera-Muñoz A, Marquez-Expósito L, Rayego-Mateos S, Rodrigues-Diez RR, Tejedor L, et al. (2020). IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis. Biomolecules, 10(10). https://doi.org/10.3390/biom10101361

[11] Witowski J, Kamhieh-Milz J, Kawka E, Catar R, & Jörres A. (2018). IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives. Front Physiol, 9, 1694. https://doi.org/10.3389/fphys.2018.01694

[12] Rodrigues-Díez R, Aroeira LS, Orejudo M, Bajo MA, Heffernan JJ, Rodrigues-Díez RR, et al. (2014). IL-17A is a novel player in dialysis-induced peritoneal damage. Kidney Int, 86(2), 303–315. https://doi.org/10.1038/ki.2014.33

[13] Huang L. (2024). The role of IL-17 family cytokines in cardiac fibrosis. Front Cardiovasc Med, 11, 1470362. https://doi.org/10.3389/fcvm.2024.1470362

[14] Xiao H, Peng L, Jiang D, Liu Y, Zhu L, Li Z, et al. (2022). IL-17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells. J Cell Mol Med, 26(22), 5728–5741. https://doi.org/10.1111/jcmm.17600

[15] Poniewierska-Baran, Tabarkiewicz, Radzikowska, Tynecka, & Eljaszewicz. (2024). The pivotal role of IL-17A in hepatic stellate cell activation. Cent Eur J Immunol, 49(4), 331. https://doi.org/10.5114/ceji.2024.146900

[16] Liu F, Wang J, Sun Z, & Yu X. (2025). Rehmannioside A alleviates renal inflammation and fibrosis in hypertensive nephropathy via AT1R/MAPK14/IL-17 signaling pathway. Biochem Biophys Res Commun, 776, 152237. https://doi.org/10.1016/j.bbrc.2025.152237

[17] Zhou YN, Xia JK, Shi CR, He Y, & Shang SL. (2025). Crosstalk Between Th17 Cells and Renal Tubular Epithelial Cells Promotes Fibrotic Progression in IgA Nephropathy. Curr Med Sci, 45(3), 626–639. https://doi.org/10.1007/s11596-025-00068-6

[18] Chung SH, Heimbürger O, & Lindholm B. (2008). Poor outcomes for fast transporters on PD: the rise and fall of a clinical concern. Semin Dial, 21(1), 7–10. https://doi.org/10.1111/j.1525-139X.2007.00327.x

[19] Huang G, Wang Y, Shi Y, Ma X, Tao M, Zang X, et al. (2021). The prognosis and risk factors of baseline high peritoneal transporters on patients with peritoneal dialysis. J Cell Mol Med, 25(18), 8628–8644. https://doi.org/10.1111/jcmm.16819

[20] González-Mateo GT, Fernández-Míllara V, Bellón T, Liappas G, Ruiz-Ortega M, López-Cabrera M, et al. (2014). Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production. PLoS One, 9(10), e108477. https://doi.org/10.1371/journal.pone.0108477

[21] Ferrantelli E, Liappas G, Vila Cuenca M, Keuning ED, Foster TL, Vervloet MG, et al. (2016). The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL-17 dependent pathways during peritoneal dialysis. Kidney Int, 89(3), 625–635. https://doi.org/10.1016/j.kint.2015.12.005

[22] Ito Y, Sun T, Tawada M, Kinashi H, Yamaguchi M, Katsuno T, et al. (2024). Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis. Int J Mol Sci, 25(16). https://doi.org/10.3390/ijms25168607

[23] Helmke A, Hüsing AM, Gaedcke S, Brauns N, Balzer MS, Reinhardt M, et al. (2021). Peritoneal dialysate-range hypertonic glucose promotes T-cell IL-17 production that induces mesothelial inflammation. Eur J Immunol, 51(2), 354–367. https://doi.org/10.1002/eji.202048733

[24] Li XR, Yang SK, Zeng BY, Tian J, Liu W, & Liao XC. (2023). Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study. Nefrologia (Engl Ed), 43(3), 335–343. https://doi.org/10.1016/j.nefroe.2022.12.001

[25] Huang Q, Xiao R, Lu J, Zhang Y, Xu L, Gao J, et al. (2022). Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling. Front Pharmacol, 13, 973182. https://doi.org/10.3389/fphar.2022.973182

[26] Lurje I, Gaisa NT, Weiskirchen R, & Tacke F. (2023). Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies. Mol Aspects Med, 92, 101191. https://doi.org/10.1016/j.mam.2023.101191

[27] Zhang Y, Feng W, Peng X, Zhu L, Wang Z, Shen H, et al. (2022). Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-β/Smad signaling axis. Lab Invest, 102(12), 1346–1354. https://doi.org/10.1038/s41374-022-00834-3

[28] Shao X, Yao L, Fu J, He M, & Zhang P. (2024). Differential expression and clinical significance of IGF2BP3 in peritoneal dialysate of patients with varying duration of peritoneal dialysis. Clin Transl Sci, 17(4), e13774. https://doi.org/10.1111/cts.13774