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Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab

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Abstract

Muckle-Wells syndrome (MWS) is a rare hereditary autoinflammatory disorder characterized by recurrent urticaria-like skin rashes, arthralgias, conjunctivitis, hypoacusia, and risk of reactive AA amyloidosis due to the progressive accumulation of amyloid fibrils in different organs. Its genetic defect lies in mutations in the NLRP3 gene, encoding the cryopyrin protein, and resulting in interleukin (IL)-1β oversecretion. Renal involvement, in terms of proteinuria or renal insufficiency, can be observed in up to 25 % of patients. Herein, we describe our experience with two Caucasian patients, father and son, aged 52 and 26 years, respectively, heterozygous for both V198M and R260W NLRP3 mutations who had AA amyloid deposits on renal biopsy. The fully human monoclonal antibody canakinumab, providing selective and prolonged IL-1β blockade, was administered in both patients every 60 days over a period of 18 months. This treatment allowed to obtain amazing results: a rapid disappearance of any clinical symptoms, the stable normalization of serum amyloid-A and, furthermore, a marked improvement of glomerular filtration rate and proteinuria with no adverse events. Our data, though limited to only two patients, emphasize that therapeutic intervention with canakinumab, suppressing both inflammation and IL-1β-mediated manifestations, can contribute to improve kidney function in MWS with overt renal amyloidosis.

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References

  1. Cantarini L, Rigante D, Brizi MG, Lucherini OM, Sebastiani GD, Vitale A, Gianneramo V, Galeazzi M (2012) Clinical and biochemical landmarks in systemic autoinflammatory diseases. Ann Med 44:664–673

    Article  PubMed  Google Scholar 

  2. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Aganna E, Martinon F, Hawkins PN, Ross JB, Swan DC, Booth DR, Lachmann HJ, Bybee A, Gaudet R, Woo P, Feighery C, Cotter FE, Thome M, Hitman GA, Tschopp J, McDermott MF (2002) Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum 46:2445–2452

    Article  CAS  PubMed  Google Scholar 

  4. Rigante D (2012) The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmun Rev 11:348–356

    Article  PubMed  Google Scholar 

  5. Cantarini L, Lucherini OM, Frediani B, Brizi MG, Bartolomei B, Cimaz R, Galeazzi M, Rigante D (2011) Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol 24:827–836

    CAS  PubMed  Google Scholar 

  6. van der Hilst JC, Drenth JPH, Simon A (2005) Hereditary periodic fever and reactive amyloidosis. Clin Exp Med 5:87–98

    Article  PubMed  Google Scholar 

  7. Kümmerle-Deschner JB, Tyrrell PN, Reess F, Kötter I, Lohse P, Girschick H, Huemer C, Horneff G, Haas JP, Koitschev A, Deuter C, Benseler SM (2010) Risk factors for severe Muckle-Wells syndrome. Arthritis Rheum 62:3783–3791

    Article  PubMed  Google Scholar 

  8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:5–14

    Article  Google Scholar 

  9. Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, Hawkins PN (2007) Natural history and outcome in systemic AA amyloidosis. N Engl J Med 356:2361–2371

    Article  CAS  PubMed  Google Scholar 

  10. Banypersad SM, Moon JC, Whelan C, Hawkins PN, Wechalekar AD (2012) Updates in cardiac amyloidosis: a review. J Am Heart Assoc 1:e000364

    Article  PubMed Central  PubMed  Google Scholar 

  11. Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S, Wittkowski H, Bek S, Hartmann N, Bosset S, Hawkins PN, Jung T (2009) In vivo regulation of interleukin 1β in patients with cryopyrin associated periodic syndromes. J Exp Med 206:1029–1036

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Hazenberg BP, van Gameren II, Bijzet J, Jager PL, van Rijswijk MH (2004) Diagnostic and therapeutic approach of systemic amyloidosis. Neth J Med 62:121–128

    CAS  PubMed  Google Scholar 

  13. Enríquez R, Sirvent AE, Padilla S et al (2013) Nephrotic syndrome and AA amyloidosis revealing adult-onset cryopyrin-associated periodic syndrome. Ren Fail 35:738–741

    Article  PubMed  Google Scholar 

  14. Merlini G, Bellotti V (2003) Molecular mechanisms of amyloidosis. N Engl J Med 349:583–596

    Article  CAS  PubMed  Google Scholar 

  15. Zhu X, Liu F, Liu Y, Liu H, Xu X, Peng Y, Sun L, Yuan S (2011) Analysis of clinical and pathological characteristics of 28 cases with renal amyloidosis. Clin Lab 57:947–952

    CAS  PubMed  Google Scholar 

  16. Hazenberg BP (2013) Amyloidosis: a clinical overview. Rheum Dis Clin North Am 39:323–345

    Article  PubMed  Google Scholar 

  17. Gertz MA, Kyle RA (1994) Amyloidosis: prognosis and treatment. Semin Arthritis Rheum 24:124–138

    Article  CAS  PubMed  Google Scholar 

  18. Gillmore JD, Lovat LB, Persey MR, Pepys MB, Hawkins PN (2001) Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet 358(9275):24–29

    Article  CAS  PubMed  Google Scholar 

  19. Yilmaz M, Unsal A, Sokmen M, Kaptanogullari OH, Alkim C, Kabukcuoglu F, Ozagari A, Bor E (2013) Renal involvement in AA amyloidosis: clinical outcomes and survival. Kidney Blood Press Res 37:33–42

    Article  CAS  PubMed  Google Scholar 

  20. Tonelli M, Sacks F, Pfeffer M, Jhangri GS, Curhan G (2005) Cholesterol and Recurrent Events (CARE) Trial Investigators. Biomarkers of inflammation and progression of chronic kidney disease. Kidney Int 68:237–2345

    Article  CAS  PubMed  Google Scholar 

  21. Vilaysane A, Chun J, Seamone ME, Wang W, Chin R, Hirota S, Li Y, Clark SA, Tschopp J, Trpkov K, Hemmelgarn BR, Beck PL, Muruve DA (2010) The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 21:1732–1744

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN, Canakinumab in CAPS Study Group (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 360:2416–2425

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Nephrology and Dialysis Unit, Department of Medicine, “Guglielmo da Saliceto” Hospital AUSL Piacenza, via Taverna 49, Piacenza, 29121, Italy

    Roberto Scarpioni, Marco Ricardi, Vittorio Albertazzi & Luigi Melfa

  2. Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy

    Donato Rigante

  3. Research Center of Systemic Autoimmune and Autoinflammatory Diseases Rheumatology Unit, Policlinico “Le Scotte” University of Siena, Siena, Italy

    Luca Cantarini

  4. Haematology Unit, Department of Oncohematology, “Guglielmo da Saliceto” Hospital AUSL Piacenza, Piacenza, Italy

    Antonio Lazzaro

Authors
  1. Roberto Scarpioni
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  2. Donato Rigante
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  3. Luca Cantarini
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  4. Marco Ricardi
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  5. Vittorio Albertazzi
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  6. Luigi Melfa
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  7. Antonio Lazzaro
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Correspondence to Roberto Scarpioni.

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Scarpioni, R., Rigante, D., Cantarini, L. et al. Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab. Clin Rheumatol 34, 1311–1316 (2015). https://doi.org/10.1007/s10067-013-2481-2

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  • DOI: https://doi.org/10.1007/s10067-013-2481-2

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