International Journal of Hematology

, Volume 109, Issue 2, pp 147–153 | Cite as

Late-stage myeloma invades kidney without significant effect on renal function: findings from 53 autopsies in a single institute

  • Junichiro Takano
  • Sohtaro Mine
  • Makoto Mochizuki
  • Noriko Tanaka
  • Shotaro HagiwaraEmail author
Original Article


Renal manifestations of multiple myeloma (MM) including cast nephropathy, amyloidosis, and renal calcification have been widely recognized. However, the severity of histopathological findings has not been addressed so far, and the clinical significance of these pathological findings is unclear. We sought to clarify the relationship between the severity of renal pathology and clinical characteristics. We analyzed 53 autopsies performed on patients who died from MM. The kidneys were evaluated using light microscopy, and the severity of pathological findings was recorded. The most common renal lesion was cast nephropathy (n = 27). Other findings included amyloidosis (n = 10), renal calcification (n = 5), microbial infection (n = 4), and MM infiltration (n = 17). The incidence of MM infiltration was substantially higher than previously reported. Renal MM infiltration was detected even when bone marrow plasmacytosis was limited. However, a significantly higher degree of renal MM infiltration was observed when MM cells invaded the liver. No correlation was observed between serum creatinine levels and degree of MM infiltration, but these tended to be elevated when cast nephropathy was severe. These findings may provide clues to understand both renal injury and extramedullary diseases in patients with MM.


Multiple myeloma Renal injury Renal infiltration by myeloma Cast nephropathy Extramedullary disease 



We are deeply grateful to Dr. Akiyoshi Miwa, Dr. Akira Tanimura, Dr. Risen Hirai, and Dr. Masataka Takeshita.

Author contributions

JT analyzed the data and wrote the paper. SM and MM evaluated the kidney samples. NT contributed essential advice regarding data analysis. SH designed the study.

Compliance with ethical standards

Conflict of interest

The authors have no competing interests.

Ethical standards

All procedures followed were in accordance with the ethical standards of the, responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.


  1. 1.
    Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the international myeloma working group. J Clin Oncol. 2010;28:4976–84.CrossRefGoogle Scholar
  2. 2.
    Bell ET. Renal lesions associated with multiple myeloma. Am J Pathol. 1993;9:393–420.Google Scholar
  3. 3.
    Herrera GA, Joseph L, Gu X, Hough A, Barlogie B. Renal pathologic spectrum in an autopsy series of patients with plasma cell dyscrasia. Arch Pathol Lab Med. 2004;128:875–9.Google Scholar
  4. 4.
    Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 1991;324:1845–52.CrossRefGoogle Scholar
  5. 5.
    Dimopoulos MA, Kastritis E, Rosinol L, Bladé J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008;22:1485–93.CrossRefGoogle Scholar
  6. 6.
    Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol. 2011;8:43–51.CrossRefGoogle Scholar
  7. 7.
    Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med. 1990;150:1693–5.CrossRefGoogle Scholar
  8. 8.
    Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1990; 58:665–683.Google Scholar
  9. 9.
    Buxbaum J. Mechanisms of disease: monoclonal immunoglobulin deposition. Amyloidosis, light chain deposition disease, and light and heavy chain deposition disease. Hematol Oncol Clin North Am. 1992;6:323–46.CrossRefGoogle Scholar
  10. 10.
    Herrera GA, Picken MM. Renal diseases associated with plasma cell dyscrasias, amyloidosis, Waldenström macroglobulinemia and cryoglobulinemic nephropathies. In: Jennette JC, Olson JL, Schwartz MM, Silvia FG, editors. Heptinstall’s pathology of the kidney. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. pp. 853–910.Google Scholar
  11. 11.
    Hanawa S, Akimoto T, Uehara E, Inoue M, Imai T, Kotoda A, et al. Renal failure caused by plasma cell infiltration in multiple myeloma. Clin Exp Nephrol. 2011;15:586–90.CrossRefGoogle Scholar
  12. 12.
    Zlotnick A, Rosenmann E. Renal pathologic findings associated with monoclonal gammopathies. Arch Intern Med. 1975;135:40–5.CrossRefGoogle Scholar
  13. 13.
    Varettoni M, Corso A. Pica G, Mangiacavalli S, Pascutto C, Lazzarino M. Incidence, presenting features and outcomes of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol. 2010;21:325–30.CrossRefGoogle Scholar
  14. 14.
    Wu P, Davies F, Boyd K, Thomas K, Dines S, Saso RM, et al. The impact of extramedullary disease at presentation in the outcome of myeloma. Leuk Lymphoma. 2009;50:230–5.CrossRefGoogle Scholar
  15. 15.
    Durie BG. The role of anatomic and functional staging in myeloma: description of Durie/Salmon Plus staging system. Eur J Cancer. 2006;42:1539–43.CrossRefGoogle Scholar
  16. 16.
    Durie BG, Waxman M, D’Agnolo AD, Williams CM. Whole body F-FDG PET identifies high-risk myeloma. J Nucl Med. 2002;43:1457–63.Google Scholar
  17. 17.
    Nakajima K, Sueki Y, Koshiishi M, Kawashima I, Nozaki Y, Mitsumori T, et al. Gastric invasion of multiple myeloma presenting as gastrointestinal bleeding. Int J Hematol. 2015;101:525–6.CrossRefGoogle Scholar
  18. 18.
    Valentina Marchica F, Accardi P, Storti C, Mancini E, Martella BD, Palma, et al. Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin? Int J Hematol. 2017;105:104–8.CrossRefGoogle Scholar
  19. 19.
    Takano J, Ohikata K, Nagase D, Igari T, Natori K, Hagiwara S. Large plasmacytoma occupying the upper limb in a myeloma patient. Rare Tumors. 2017;9:5866.CrossRefGoogle Scholar
  20. 20.
    Wirk B, Wingard JR, Moreb JS. Extramedullary disease in plasma cell myeloma: the iceberg phenomenon. Bone Marrow Transplant. 2013;48:10–8.CrossRefGoogle Scholar
  21. 21.
    Blade J, Fernández de Larrea C, Rosiñol L, Cibeira MT, Jiménez R, Powles R. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29:3805–12.CrossRefGoogle Scholar
  22. 22.
    Montseny JJ, Kleinknecht D, Meyrier A, Vanhille P, Simon P, Pruna A, et al. Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies. Nephrol Dial Transplant. 1998;13:1438–45.CrossRefGoogle Scholar
  23. 23.
    Nasr SH, Valeri AM, Sethi S, Fidler ME, Cornell LD, Gertz MA, et al. Clinicopathologic correlations in multiple myeloma: a case series of 190 patients with kidney biopsies. Am J Kidney Dis. 2012;59:786–94.CrossRefGoogle Scholar
  24. 24.
    Alegre A, Granda A, Martinez-Chamorro C, Diaz-Mediavilla J, Martinez R, Garcia-Larana, et al. Spanish Registry of Transplants in Multiple Myelomas, Spanish Group of Hemopoietic Transplant (GETH), PETHEMA. Different patterns of relapse after autologous peripheral blood stem cell transplantation in multiple myeloma: clinical results of 280 cases from the Spanish Registry. Haematologica. 2002;87:609–14.Google Scholar
  25. 25.
    Barlogie B, Smallwood L, Smith T, Alexanian R. High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma. Ann Intern Med. 1989;110:521–5.CrossRefGoogle Scholar
  26. 26.
    Cherng NC, Asal NR, Kuebler JP, Lee ET, Solanki D. Prognostic factors in multiple myeloma. Cancer. 1991;67:3150–6.CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Junichiro Takano
    • 1
  • Sohtaro Mine
    • 1
  • Makoto Mochizuki
    • 2
  • Noriko Tanaka
    • 3
  • Shotaro Hagiwara
    • 1
    • 4
    Email author
  1. 1.Division of Hematology, Internal MedicineNational Center for Global Health and MedicineTokyoJapan
  2. 2.Department of Clinical Laboratory Science, Faculty of Medical TechnologyTeikyo UniversityTokyoJapan
  3. 3.Biostatistics Section, Department of Clinical Study and Informatics, Center for Clinical ScienceNational Center for Global Health and MedicineTokyoJapan
  4. 4.Department of HematologyTokyo Women’s Medical UniversityTokyoJapan

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