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Preliminary Communication

Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study

    Yuka Sugawara

    Division of Nephrology & Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, 113 8655, Japan

    ,
    Yosuke Hirakawa

    Division of Nephrology & Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, 113 8655, Japan

    ,
    Koki Mise

    Department of Nephrology, Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, 700 8558, Japan

    ,
    Kosuke Kashiwabara

    Data Science Office, Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, 113 8655, Japan

    ,
    Ko Hanai

    Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, 162 8666, Japan

    ,
    Satoshi Yamaguchi

    Department of Nephrology, Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, 700 8558, Japan

    ,
    Akihiro Katayama

    Department of Nephrology, Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, 700 8558, Japan

    ,
    Yasuhiro Onishi

    Department of Nephrology, Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, 700 8558, Japan

    ,
    Yui Yoshida

    Division of Nephrology & Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, 113 8655, Japan

    ,
    Naoki Kashihara

    Department of Nephrology & Hypertension, Kawasaki Medical School, Kurashiki, 701 0192, Japan

    ,
    Yutaka Matsuyama

    Department of Biostatistics, The University of Tokyo, Tokyo, 113 0033, Japan

    ,
    Tetsuya Babazono

    Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, 162 8666, Japan

    ,
    Masaomi Nangaku

    *Author for correspondence: Tel.: +81 338 155 411; Ext.: 35730, 35154;

    E-mail Address: mnangaku@m.u-tokyo.ac.jp

    Division of Nephrology & Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, 113 8655, Japan

    &
    Jun Wada

    Department of Nephrology, Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, 700 8558, Japan

    Published Online:https://doi.org/10.2217/bmm-2021-1104

    Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

    Papers of special note have been highlighted as: • of interest

    References

    • 1. American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes – 2021. Diabetes Care 44(Suppl. 1), S125–S150 (2021).
    • 2. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N. Engl. J. Med. 311(2), 89–93 (1984).
    • 3. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity–diabetes link. Diabetes 43(11), 1271–1278 (1994).
    • 4. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286(3), 327–334 (2001).
    • 5. Coca SG, Nadkarni GN, Huang Y et al. Plasma biomarkers and kidney function decline in early and established diabetic kidney disease. J. Am. Soc. Nephrol. 28(9), 2786–2793 (2017). • This paper is important in the sense that it demonstrates the usefulness of sTNFR-1 and sTNFR-2 as biomarkers.
    • 6. Niewczas MA, Pavkov ME, Skupien J et al. A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes. Nat. Med. 25(5), 805–813 (2019). • This paper examines 194 circulating inflammatory cytokines and reports that 17 of them may be useful as biomarkers.
    • 7. Kamei N, Yamashita M, Nishizaki Y et al. Association between circulating tumor necrosis factor-related biomarkers and estimated glomerular filtration rate in type 2 diabetes. Sci. Rep. 8(1), 15302 (2018). • This paper reports that sTNFR-1 and sTNFR-2 are associated with lower eGFR in Japanese diabetic patients.
    • 8. Cao L, Boston A, Jegede O et al. Inflammation and kidney injury in diabetic African American men. J. Diabetes Res. 2019, 5359635 (2019).
    • 9. Mise K, Imamura M, Yamaguchi S et al. Identification of novel urinary biomarkers for predicting renal prognosis in patients with type 2 diabetes by glycan profiling in a multicenter prospective cohort study: U-CARE study 1. Diabetes Care 41(8), 1765–1775 (2018).
    • 10. Seino Y, Nanjo K, Tajima N et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J. Diabetes Investig. 1(5), 212–228 (2010).
    • 11. Matsuo S, Imai E, Horio M et al. Revised equations for estimated GFR from serum creatinine in Japan. Am. J. Kidney Dis. 53(6), 982–992 (2009).
    • 12. Kashiwagi A, Kasuga M, Araki E et al. International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J. Diabetes Investig. 3(1), 39–40 (2012).
    • 13. Levin A, Stevens PE, Bilous RW et al. Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Supple. 3(1), 1–150 (2013).
    • 14. Lima-Oliveira G, Monneret D, Guerber F, Guidi GC. Sample management for clinical biochemistry assays: are serum and plasma interchangeable specimens? Crit. Rev. Clin. Lab. Sci. 55(7), 480–500 (2018).
    • 15. Krolewski AS, Skupien J, Rossing P, Warram JH. Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes. Kidney Int. 91(6), 1300–1311 (2017).
    • 16. Seo DH, Nam M, Jung M et al. Serum levels of adipocyte fatty acid-binding protein are associated with rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function. Diabetes. Metab. J. 44(6), 875–886 (2020).
    • 17. Colombo M, Mcgurnaghan SJ, Bell S et al. Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus. Diabetologia 63(3), 636–647 (2020).
    • 18. Limonte CP, Valo E, Montemayor D et al. A targeted multiomics approach to identify biomarkers associated with rapid eGFR decline in type 1 diabetes. Am. J. Nephrol. 51(10), 839–848 (2020).
    • 19. Jiang W, Wang J, Shen X et al. Establishment and validation of a risk prediction model for early diabetic kidney disease based on a systematic review and meta-analysis of 20 cohorts. Diabetes Care 43(4), 925–933 (2020).
    • 20. Halvorsen B, Santilli F, Scholz H et al. LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro. Diabetologia 59(10), 2134–2144 (2016). • This paper shows that the levels of LIGHT are elevated in the patients with type 2 diabetes mellitus, and by reading this you will also get an overview of LIGHT.
    • 21. Ware CF. Targeting the LIGHT-HVEM pathway. Adv. Exp. Med. Biol. 647, 146–155 (2009).
    • 22. Gomez IG, Roach AM, Nakagawa N et al. TWEAK-Fn14 signaling activates myofibroblasts to drive progression of fibrotic kidney disease. J. Am. Soc. Nephrol. 27(12), 3639–3652 (2016). • This study suggests that the TWEAK-Fn14 signaling pathway is important in chronic kidney disease progression using in vivo and in vitro experiments.
    • 23. Burkly LC. Regulation of tissue responses: The TWEAK/Fn14 oathway and other TNF/TNFR superfamily members that activate non-canonical NFκB signaling. Front. Immunol. 6, 92 (2015).
    • 24. Chicheportiche Y, Bourdon PR, Xu H et al. TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J. Biol. Chem. 272(51), 32401–32410 (1997).
    • 25. Justo P, Sanz AB, Sanchez-Niño MD et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int. 70(10), 1750–1758 (2006). • This paper suggests that cooperation between inflammatory cytokines, such as TWEAK and Fn14, may play a role in renal tubular cell injury.
    • 26. Sastre C, Fernández-Laso V, Madrigal-Matute J et al. Genetic deletion or TWEAK blocking antibody administration reduce atherosclerosis and enhance plaque stability in mice. J. Cell. Mol. Med. 18(4), 721–734 (2014).
    • 27. Muñoz-García B, Moreno JA, López-Franco O et al. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice. Arterioscler. Thromb. Vasc. Biol. 29(12), 2061–2068 (2009).
    • 28. Fernández-Laso V, Méndez-Barbero N, Valdivielso JM et al. Soluble TWEAK and atheromatosis progression in patients with chronic kidney disease. Atherosclerosis 260, 130–137 (2017).
    • 29. Liu SY, Chen J, Li YF. Clinical significance of serum interleukin-8 and soluble tumor necrosis factor-like weak inducer of apoptosis levels in patients with diabetic nephropathy. J. Diabetes Investig. 9(5), 1182–1188 (2018).
    • 30. Baud L, Ardaillou R. Tumor necrosis factor in renal injury. Miner. Electrolyte. Metab. 21(4–5), 336–341 (1995).