, Volume 78, Issue 11, pp 1073–1083 | Cite as

The Future of IL-1 Targeting in Kidney Disease

  • Baris Afsar
  • Adrian Covic
  • Alberto Ortiz
  • Rengin Elsurer Afsar
  • Mehmet Kanbay
Leading Article


Interleukin (IL)-1α and IL-1β are proinflammatory cytokines that play a role in many diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, gout, and periodic inflammatory syndromes, including familial Mediterranean fever and Muckle-Wells syndrome. Drugs targeting IL-1 such as recombinant IL-1Ra (anakinra), neutralizing anti-IL-1β antibodies (canakinumab) and IL-1β traps (rilonacept) are in clinical use to treat these diseases. Additionally, experimental evidence suggests a role of IL-1 in kidney disease and hypertension and targeting IL-1 showed promising results in high cardiovascular risk patients, hemodialysis and renal transplantation patients. We now summarize knowledge on the potential role of IL-1 targeting in patients with kidney disease.


Compliance with Ethical Standards


Research of the authors has been supported by grants from Instituto de Salud Carlos III, Red REDinREN RD 16/0009, FIS AO was supported by FIS PI16 02057, FEDER funds ISCIII-RETIC REDinREN RD16/0009, Sociedad Española de Nefrología. Adrian Covic was supported by a grant of Ministry of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2016-0908, Contract number 167/2017, within PNCDI III.

Conflict of interest

Alberto Ortiz has served as a consultant for Sanofi and Servier, received speaker fees Amgen, Otsuka, and Shire. Adrian Covic has served as consultant to Fresenius. Mehmet Kanbay and Baris Afsar declare no potential conflicts of interest with the contents of this manuscript.


  1. 1.
    Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39:1003–18.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    O’Neill LA. How does interleukin-1 activate cells? Kidney Int. 1992;41:546–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Black RA, Kronheim SR, Cantrell M, Deeley MC, March CJ, Prickett KS, Wignall J, Conlon PJ, Cosman CD, Hopp TP, et al. Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor. J Biol Chem. 1988;263:9437–42.PubMedGoogle Scholar
  4. 4.
    Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–65.PubMedCrossRefGoogle Scholar
  5. 5.
    Martin-Sanchez D, Poveda J, Fontecha-Barriuso M, Ruiz-Andres O, Sanchez-Nino MD, Ruiz-Ortega M, Ortiz A, Sanz AB. Targeting of regulated necrosis in kidney disease. Nefrologia. 2018;38:125–35.PubMedCrossRefGoogle Scholar
  6. 6.
    de Torre-Minguela C, Mesa Del Castillo P, Pelegrin P. The NLRP3 and pyrin inflammasomes: implications in the pathophysiology of autoinflammatory diseases. Front Immunol. 2017;8:43.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Guma M, Ronacher L, Liu-Bryan R, Takai S, Karin M, Corr M. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 2009;60:3642–50.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Joosten LA, Netea MG, Fantuzzi G, Koenders MI, Helsen MM, Sparrer H, Pham CT, van der Meer JW, Dinarello CA, van den Berg WB. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin- 1beta. Arthritis Rheum. 2009;60:3651–62.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20:S1–13.PubMedGoogle Scholar
  10. 10.
    Dinarello CA. Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism. Int J Tissue React. 1992;14:65–75.PubMedGoogle Scholar
  11. 11.
    Carter DB, Deibel MR Jr, Dunn CJ, Tomich CS, Laborde AL, Slightom JL, Berger AE, Bienkowski MJ, Sun FF, McEwan RN, et al. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990;344:633–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Dripps DJ, Brandhuber BJ, Thompson RC, Eisenberg SP. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem. 1991;266:10331–6.PubMedGoogle Scholar
  13. 13.
    van Kooten C, van der Linde X, Woltman AM, van Es LA, Daha MR. Synergistic effect of interleukin-1 and CD40L on the activation of human renal tubular epithelial cells. Kidney Int. 1999;56:41–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Baud L, Fouqueray B, Bellocq A. Switching off renal inflammation by anti-inflammatory mediators: the facts, the promise and the hope. Kidney Int. 1998;53:1118–26.PubMedCrossRefGoogle Scholar
  15. 15.
    Cao Y, Jiao Y, Wang L, Huang Y, Postlethwaite A, Stuart J, Kang A, Williams RW, Gu W. Anakinra as an interleukin 1 receptor antagonist, complicated genetics and molecular impacts-from the point of view of mouse genomics. Int Immunopharmacol. 2012;13:28–36.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Schreiber A, Pham CT, Hu Y, Schneider W, Luft FC, Kettritz R. Neutrophil serine proteases promote IL-1beta generation and injury in necrotizing crescentic glomerulonephritis. J Am Soc Nephrol. 2012;23:470–82.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Tesch GH, Lan HY, Atkins RC, Nikolic-Paterson DJ. Role of interleukin-1 in mesangial cell proliferation and matrix deposition in experimental mesangioproliferative nephritis. Am J Pathol. 1997;151:141–50.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Tateyama F, Yamabe H, Osawa H, Kaizuka M, Shirato K, Okumura K. Interleukin-1beta is an autocrine growth factor of rat glomerular epithelial cells in culture. Nephrol Dial Transplant. 2001;16:1149–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Lovett DH, Larsen A. Cell cycle-dependent interleukin 1 gene expression by cultured glomerular mesangial cells. J Clin Invest. 1988;82:115–22.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Akash MS, Rehman K, Sun H, Chen S. Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats. PLoS One. 2013;8:e55925.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Dinarello CA. Interleukin-1beta. Crit Care Med. 2005;33:S460–2.PubMedCrossRefGoogle Scholar
  22. 22.
    Alique M, Sanchez-Lopez E, Rayego-Mateos S, Egido J, Ortiz A, Ruiz-Ortega M. Angiotensin II, via angiotensin receptor type 1/nuclear factor-kappaB activation, causes a synergistic effect on interleukin-1-beta-induced inflammatory responses in cultured mesangial cells. J Renin Angiotensin Aldosterone Syst. 2015;16:23–32.PubMedCrossRefGoogle Scholar
  23. 23.
    Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-kappaB. Trends Cell Biol. 2017;27:417–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Sanz AB, Sanchez-Nino MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M, Egido J, Ortiz A. NF-kappaB in renal inflammation. J Am Soc Nephrol. 2010;21:1254–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Moreno JA, Izquierdo MC, Sanchez-Nino MD, Suarez-Alvarez B, Lopez-Larrea C, Jakubowski A, Blanco J, Ramirez R, Selgas R, Ruiz-Ortega M, et al. The inflammatory cytokines TWEAK and TNF alpha reduce renal klotho expression through NF kappaB. J Am Soc Nephrol. 2011;22:1315–25.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Ruiz-Ortega M, Ruperez M, Esteban V, Rodriguez-Vita J, Sanchez-Lopez E, Carvajal G, Egido J. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transpl. 2006;21:16–20.CrossRefGoogle Scholar
  27. 27.
    Ruiz-Ortega M, Bustos C, Hernandez-Presa MA, Lorenzo O, Plaza JJ, Egido J. Angiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-1 synthesis. J Immunol. 1998;161:430–9.PubMedGoogle Scholar
  28. 28.
    Joshi-Barve SS, Rangnekar VV, Sells SF, Rangnekar VM. Interleukin-1-inducible expression of grobeta via NF-kappa B activation is dependent upon tyrosine kinase signaling. J Biol Chem. 1993;268:18018–29.PubMedGoogle Scholar
  29. 29.
    Taneja N, Coy PE, Lee I, Bryson JM, Robey RB. Proinflammatory interleukin-1 cytokines increase mesangial cell hexokinase activity and hexokinase II isoform abundance. Am J Physiol Cell Physiol. 2004;287:C548–57.PubMedCrossRefGoogle Scholar
  30. 30.
    An LL, Mehta P, Xu L, Turman S, Reimer T, Naiman B, Connor J, Sanjuan M, Kolbeck R, Fung M. Complement C5a potentiates uric acid crystal-induced IL-1beta production. Eur J Immunol. 2014;44:3669–79.PubMedCrossRefGoogle Scholar
  31. 31.
    Barratt-Due A, Thorgersen EB, Egge K, Pischke S, Sokolov A, Hellerud BC, Lindstad JK, Pharo A, Bongoni AK, Rieben R, et al. Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis. J Immunol. 2013;191:819–27.PubMedCrossRefGoogle Scholar
  32. 32.
    Yang H, Tuzun E, Alagappan D, Yu X, Scott BG, Ischenko A, Christadoss P. IL-1 receptor antagonist-mediated therapeutic effect in murine myasthenia gravis is associated with suppressed serum proinflammatory cytokines, C3, and anti-acetylcholine receptor IgG1. J Immunol. 2005;175:2018–25.PubMedCrossRefGoogle Scholar
  33. 33.
    Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, Monticelli S, Lanzavecchia A, Sallusto F. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta. Nature. 2012;484:514–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17- producing human T helper cells. Nat Immunol. 2007;8:942–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Ilarregui JM, van Beelen AJ, Fehres CM, Bruijns SC, Garcia-Vallejo JJ, van Kooyk Y. New roles for CD14 and IL-beta linking inflammatory dendritic cells to IL-17 production in memory CD4(+) T cells. Immunol Cell Biol. 2016;94:907–16.PubMedCrossRefGoogle Scholar
  36. 36.
    Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity. 2009;30:576–87.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Shaw MH, Kamada N, Kim YG, Nunez G. Microbiota-induced IL-1beta, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J Exp Med. 2012;209:251–8.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Suurmond J, Habets KL, Dorjee AL, Huizinga TW, Toes RE. Expansion of Th17 cells by human mast cells is driven by inflammasome-independent IL-1beta. J Immunol. 2016;197:4473–81.PubMedCrossRefGoogle Scholar
  39. 39.
    Park MJ, Lee SH, Lee SH, Lee EJ, Kim EK, Choi JY, Cho ML. IL-1 receptor blockade alleviates graftversus- host disease through downregulation of an interleukin-1beta-dependent glycolytic pathway in th17 cells. Mediat Inflamm. 2015;2015:631384.Google Scholar
  40. 40.
    Poveda J, Sanz AB, Rayego-Mateos S, Ruiz-Ortega M, Carrasco S, Ortiz A, Sanchez-Nino MD. NFkappaBiz protein downregulation in acute kidney injury: modulation of inflammation and survival in tubular cells. Biochim Biophys Acta. 2016;1862:635–46.PubMedCrossRefGoogle Scholar
  41. 41.
    Elewa U, Sanchez-Nino MD, Martin-Cleary C, Fernandez-Fernandez B, Egido J, Ortiz A. Cardiovascular risk biomarkers in CKD: the inflammation link and the road less traveled. Int Urol Nephrol. 2012;44:1731–44.PubMedCrossRefGoogle Scholar
  42. 42.
    Perez-Gomez MV, Sanchez-Nino MD, Sanz AB, Zheng B, Martin-Cleary C, Ruiz-Ortega M, Ortiz A, Fernandez-Fernandez B. Targeting inflammation in diabetic kidney disease: early clinical trials. Expert Opin Investig Drugs. 2016;25:1045–58.PubMedCrossRefGoogle Scholar
  43. 43.
    Chung AC, Lan HY. Chemokines in renal injury. J Am Soc Nephrol. 2011;22:802–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Tang WW, Feng L, Vannice JL, Wilson CB. Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis. J Clin Invest. 1994;93:273–9.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Nishikawa K, Guo YJ, Miyasaka M, Tamatani T, Collins AB, Sy MS, McCluskey RT, Andres G. Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis. J Exp Med. 1993;177:667–77.PubMedCrossRefGoogle Scholar
  46. 46.
    Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, Gutierrez-Ramos JC. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med. 1997;185:1371–80.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Lan HY, Nikolic-Paterson DJ, Mu W, Vannice JL, Atkins RC. Interleukin-1 receptor antagonist halts the progression of established crescentic glomerulonephritis in the rat. Kidney Int. 1995;47:1303–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Yu XQ, Fan JM, Nikolic-Paterson DJ, Yang N, Mu W, Pichler R, Johnson RJ, Atkins RC, Lan HY. IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat. Am J Pathol. 1999;154:833–41.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Singh RP, Patarca R, Schwartz J, Singh P, Cantor H. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med. 1990;171:1931–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Tam FW, Smith J, Cashman SJ, Wang Y, Thompson EM, Rees AJ. Glomerular expression of interleukin-1 receptor antagonist and interleukin-1 beta genes in antibody-mediated glomerulonephritis. Am J Pathol. 1994;145:126–36.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Nikolic-Paterson DJ, Lan HY, Hill PA, Vannice JL, Atkins RC. Suppression of experimental glomerulonephritis by the interleukin-1 receptor antagonist: inhibition of intercellular adhesion molecule-1 expression. J Am Soc Nephrol. 1994;4:1695–700.PubMedGoogle Scholar
  52. 52.
    Karkar AM, Tam FW, Steinkasserer A, Kurrle R, Langner K, Scallon BJ, Meager A, Rees AJ. Modulation of antibody-mediated glomerular injury in vivo by IL-1ra, soluble IL-1 receptor, and soluble TNF receptor. Kidney Int. 1995;48:1738–46.PubMedCrossRefGoogle Scholar
  53. 53.
    Brown Z, Strieter RM, Neild GH, Thompson RC, Kunkel SL, Westwick J. IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells. Kidney Int. 1992;42:95–101.PubMedCrossRefGoogle Scholar
  54. 54.
    Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–147.PubMedGoogle Scholar
  55. 55.
    Kelly KJ, Williams WW Jr, Colvin RB, Meehan SM, Springer TA, Gutierrez-Ramos JC, Bonventre JV. Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. J Clin Invest. 1996;97:1056–63.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Haq M, Norman J, Saba SR, Ramirez G, Rabb H. Role of IL-1 in renal ischemic reperfusion injury. J Am Soc Nephrol. 1998;9:614–9.PubMedGoogle Scholar
  57. 57.
    Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, Muruve D, Shi Y, Munro F, Liapis H, et al. Calcium oxalate crystals induce renal inflammation by NLRP3- mediated IL-1beta secretion. J Clin Invest. 2013;123:236–46.PubMedCrossRefGoogle Scholar
  58. 58.
    Dinarello CA. Interleukin-1beta and the autoinflammatory diseases. N Engl J Med. 2009;360:2467–70.PubMedCrossRefGoogle Scholar
  59. 59.
    Zhou MS, Schulman IH, Raij L. Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension: role of nuclear factor kappa B activation. J Hypertens. 2010;28:527–35.PubMedCrossRefGoogle Scholar
  60. 60.
    Briones AM, Salaices M, Vila E. Ageing alters the production of nitric oxide and prostanoids after IL-1beta exposure in mesenteric resistance arteries. Mech Ageing Dev. 2005;126:710–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Jimenez-Altayo F, Briones AM, Giraldo J, Planas AM, Salaices M, Vila E. Increased superoxide anion production by interleukin-1beta impairs nitric oxide-mediated relaxation in resistance arteries. J Pharmacol Exp Ther. 2006;316:42–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Loughrey JP, Laffey JG, Moore BJ, Lynch F, Boylan JF, McLoughlin P. Interleukin-1 beta rapidly inhibits aortic endothelium-dependent relaxation by a DNA transcription-dependent mechanism. Crit Care Med. 2003;31:910–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Dorrance AM. Interleukin 1-beta (IL-1beta) enhances contractile responses in endothelium denuded aorta from hypertensive, but not normotensive, rats. Vascul Pharmacol. 2007;47:160–5.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Dalekos GN, Elisaf M, Bairaktari E, Tsolas O, Siamopoulos KC. Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients? J Lab Clin Med. 1997;129:300–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Peeters AC, Netea MG, Janssen MC, Kullberg BJ, Van der Meer JW, Thien T. Pro inflammatory cytokines in patients with essential hypertension. Eur J Clin Invest. 2001;31:31–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Dorffel Y, Latsch C, Stuhlmuller B, Schreiber S, Scholze S, Burmester GR, Scholze J. Preactivated peripheral blood monocytes in patients with essential hypertension. Hypertension. 1999;34:113–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Li QZ, Deng Q, Li JQ, Yi GH, Zhao SP. Valsartan reduces interleukin-1beta secretion by peripheral blood mononuclear cells in patients with essential hypertension. Clin Chim Acta. 2005;355:131–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Chamberlain J, Francis S, Brookes Z, Shaw G, Graham D, Alp NJ, Dower S, Crossman DC. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding. PLoS One. 2009;4:e5073.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Muller DN, Dechend R, Mervaala EM, Park JK, Schmidt F, Fiebeler A, Theuer J, Breu V, Ganten D, Haller H, et al. NF-kappaB inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension. 2000;35:193–201.PubMedCrossRefGoogle Scholar
  70. 70.
    Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003;74:85–94.PubMedCrossRefGoogle Scholar
  71. 71.
    Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36:1118–25.PubMedCrossRefGoogle Scholar
  72. 72.
    Fleischmann R, Stern R, Iqbal I. Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 2004;4:1333–44.PubMedCrossRefGoogle Scholar
  73. 73.
    Akar S, Cetin P, Kalyoncu U, Karadag O, Sari I, Cinar M, Yilmaz S, Onat AM, Kisacik B, Erten A, et al. A nationwide experience with the off-label use of interleukin-1 targeting treatment in familial mediterranean fever patients. Arthritis Care Res (Hoboken). 2018;70(7):1090–4. Scholar
  74. 74.
    Ben-Zvi I, Kukuy O, Giat E, Pras E, Feld O, Kivity S, Perski O, Bornstein G, Grossman C, Harari G, et al. Anakinra for colchicine-resistant familial mediterranean fever: a randomized, double-blind. Placebo-controlled trial. Arthritis Rheumatol. 2017;69:854–62.PubMedCrossRefGoogle Scholar
  75. 75.
    Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R. Colchicine-induced toxicity in a heart transplant patient with chronic renal failure. Clin Toxicol (Phila). 2008;46:827–30.CrossRefGoogle Scholar
  76. 76.
    Direz G, Noel N, Guyot C, Toupance O, Salmon JH, Eschard JP. Efficacy but side effects of anakinra therapy for chronic refractory gout in a renal transplant recipient with preterminal chronic renal failure. Joint Bone Spine. 2012;79:631.PubMedCrossRefGoogle Scholar
  77. 77.
    Peces R, Afonso S, Peces C, Nevado J, Selgas R. Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report. BMC Med Genet. 2017;18:97.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Mulders-Manders CM, Baas MC, Molenaar FM, Simon A. Peri- and postoperative treatment with the interleukin-1 receptor antagonist anakinra is safe in patients undergoing renal transplantation: case series and review of the literature. Front Pharmacol. 2017;8:342.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Celebi ZK, Kucuksahin O, Sengul S, Tuzuner A, Keven K. Colchicine-resistant familial Mediterranean fever in a renal transplantation patient: successful treatment with anakinra. Clin Kidney J. 2014;7:219–20.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Ozcakar ZB, Ozdel S, Yilmaz S, Kurt-Sukur ED, Ekim M, Yalcinkaya F. Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis. Clin Rheumatol. 2016;35:441–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Alpay N, Sumnu A, Caliskan Y, Yazici H, Turkmen A, Gul A. Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever. Rheumatol Int. 2012;32:3277–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Moser C, Pohl G, Haslinger I, Knapp S, Rowczenio D, Russel T, Lachmann HJ, Lang U, Kovarik J. Successful treatment of familial Mediterranean fever with Anakinra and outcome after renal transplantation. Nephrol Dial Transplant. 2009;24:676–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Hung AM, Ellis CD, Shintani A, Booker C, Ikizler TA. IL-1beta receptor antagonist reduces inflammation in hemodialysis patients. J Am Soc Nephrol. 2011;22:437–42.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Kuemmerle-Deschner JB, Haug I. Canakinumab in patients with cryopyrin-associated periodic syndrome: an update for clinicians. Ther Adv Musculoskelet Dis. 2013;5:315–29.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Sozeri B, Gulez N, Ergin M, Serdaroglu E. The experience of canakinumab in renal amyloidosis secondary to Familial Mediterranean fever. Mol Cell Pediatr. 2016;3:33.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Bilginer Y, Ayaz NA, Ozen S. Anti-IL-1 treatment for secondary amyloidosis in an adolescent with FMF and Behcet’s disease. Clin Rheumatol. 2010;29:209–10.PubMedCrossRefGoogle Scholar
  87. 87.
    Peiro C, Lorenzo O, Carraro R, Sanchez-Ferrer CF. IL-1beta inhibition in cardiovascular complications associated to diabetes mellitus. Front Pharmacol. 2017;8:363.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517–26.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Ridker PM, Howard CP, Walter V, Everett B, Libby P, Hensen J, Thuren T, Group CPI. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012;126:2739–48.PubMedCrossRefGoogle Scholar
  90. 90.
    Choudhury RP, Birks JS, Mani V, Biasiolli L, Robson MD, L’Allier PL, Gingras MA, Alie N, McLaughlin MA, Basson CT, et al. Arterial effects of canakinumab in patients with atherosclerosis and type 2 diabetes or glucose intolerance. J Am Coll Cardiol. 2016;68:1769–80.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.PubMedCrossRefGoogle Scholar
  92. 92.
    Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–42.PubMedCrossRefGoogle Scholar
  93. 93.
    Radin A, Marbury T, Osgood G, Belomestnov P. Safety and pharmacokinetics of subcutaneously administered rilonacept in patients with well-controlled end-stage renal disease (ESRD). J Clin Pharmacol. 2010;50:835–41.PubMedCrossRefGoogle Scholar
  94. 94.
    Nowak KL, Hung A, Ikizler TA, Farmer-Bailey H, Salas-Cruz N, Sarkar S, Hoofnagle A, You Z, Chonchol M. Interleukin-1 inhibition, chronic kidney disease-mineral and bone disorder, and physical function. Clin Nephrol. 2017;88:132–43.PubMedCrossRefGoogle Scholar
  95. 95.
    Hashkes PJ, Spalding SJ, Giannini EH, Huang B, Johnson A, Park G, Barron KS, Weisman MH, Pashinian N, Reiff AO, et al. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012;157:533–41.PubMedCrossRefGoogle Scholar
  96. 96.
    Dusser P, Kone-Paut I. IL-1 inhibition may have an important role in treating refractory Kawasaki disease. Front Pharmacol. 2017;8:163.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Tremoulet AH, Jain S, Kim S, Newburger J, Arditi M, Franco A, Best B, Burns JC. Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial). Contemp Clin Trials. 2016;48:70–5.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Ly KH, Stirnemann J, Liozon E, Michel M, Fain O, Fauchais AL. Interleukin-1 blockade in refractory giant cell arteritis. Joint Bone Spine. 2014;81:76–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Boyer EM, Turman M, O’Neil KM. Partial response to anakinra in life-threatening Henoch- Schonlein purpura: case report. Pediatr Rheumatol Online J. 2011;9:21.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Botsios C, Sfriso P, Furlan A, Punzi L, Dinarello CA. Resistant Behcet disease responsive to anakinra. Ann Intern Med. 2008;149:284–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Botsios C, Sfriso P, Punzi L, Todesco S. Non-complementaemic urticarial vasculitis: successful treatment with the IL-1 receptor antagonist, anakinra. Scand J Rheumatol. 2007;36:236–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Zuurmond AM, Koudijs A, van El B, Doornbos RP, van Manen-Vernooij BC, Bastiaans JH, Penninks AH, van Bilsen JH, Cnubben NH, Degroot J. Integration of efficacy, pharmacokinetic and safety assessment of interleukin-1 receptor antagonist in a preclinical model of arthritis. Regul Toxicol Pharmacol. 2011;59:461–70.PubMedCrossRefGoogle Scholar
  103. 103.
    Swart JF, Barug D, Mohlmann M, Wulffraat NM. The efficacy and safety of interleukin-1- receptor antagonist anakinra in the treatment of systemic juvenile idiopathic arthritis. Expert Opin Biol Ther. 2010;10:1743–52.PubMedCrossRefGoogle Scholar
  104. 104.
    Church LD, McDermott MF. Canakinumab: a human anti-IL-1beta monoclonal antibody for the treatment of cryopyrin-associated periodic syndromes. Expert Rev Clin Immunol. 2010;6:831–41.PubMedCrossRefGoogle Scholar
  105. 105.
    Alten R, Gram H, Joosten LA, van den Berg WB, Sieper J, Wassenberg S, Burmester G, van Riel P, Diaz-Lorente M, Bruin GJ, et al. The human anti-IL-1 beta monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis. Arthritis Res Ther. 2008;10:R67.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S, Wittkowski H, Bek S, Hartmann N, Bosset S, et al. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med. 2009;206:1029–36.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Goldbach-Mansky R, Shroff SD, Wilson M, Snyder C, Plehn S, Barham B, Pham TH, Pucino F, Wesley RA, Papadopoulos JH, et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 2008;58:2432–42.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, Weinstein SP, Belomestnov P, Yancopoulos GD, Stahl N, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443–52.PubMedCrossRefGoogle Scholar
  109. 109.
    Perez-Gomez MV, Sanchez-Nino MD, Sanz AB, Martin-Cleary C, Ruiz-Ortega M, Egido J, Navarro- Gonzalez JF, Ortiz A, Fernandez-Fernandez B. Horizon 2020 in diabetic kidney disease: the clinical trial pipeline for add-on therapies on top of renin angiotensin system blockade. J Clin Med. 2015;4:1325–47.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Ortiz A, Covic A, Fliser D, Fouque D, Goldsmith D, Kanbay M, Mallamaci F, Massy ZA, Rossignol P, Vanholder R, et al. Epidemiology, contributors to, and clinical trials of mortality risk in chronic kidney failure. Lancet. 2014;383:1831–43.PubMedCrossRefGoogle Scholar
  111. 111.
    Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Baris Afsar
    • 1
  • Adrian Covic
    • 2
  • Alberto Ortiz
    • 3
  • Rengin Elsurer Afsar
    • 1
  • Mehmet Kanbay
    • 4
  1. 1.Division of Nephrology, Department of MedicineSuleyman Demirel University School of MedicineIspartaTurkey
  2. 2.Nephrology Department, Dialysis and Renal Transplant Center, “Dr. C.I. Parhon” University Hospital“Grigore T. Popa” University of Medicine and PharmacyIasiRomania
  3. 3.Dialysis Unit, School of Medicine, IIS-Fundacion Jimenez DiazUniversidad Autónoma de MadridMadridSpain
  4. 4.Division of Nephrology, Department of MedicineKoc University School of MedicineIstanbulTurkey

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