Vnitr Lek 2020, 66(7):425-431 | DOI: 10.36290/vnl.2020.122

Renal failure in multiple myeloma and its treatment

Romana Ryšavá
Klinika nefrologie 1. LF UK a VFN Praha

Renal failure is a serious complication of multiple myeloma, and up to 50% of patients with this most frequent haematological malignancy may develop some form of renal impairment. The aetiology of renal damage is multifactorial, but increased production of free light chains that are filtered into the urine is crucial for the development of renal failure and could be associated with distal tubule involvement (myeloma kidney, light chain cast nephropathy) or with fully developed Fanconi syndrome in proximal tubule damage (proximal tubulopathy, light chain proximal tubulopathy). Glomerular damage most often manifests as AL amyloidosis or light chain deposition disease; both cause severe nephrotic syndrome. Early and adequate chemotherapy in association with symptomatic treatment can lead to rapid reduction of serum light chain concentration which is necessary to prevent development of renal failure. At present, effective therapeutic procedures can be used for this purpose, where especially a triple combination of treatment containing one of the proteasome inhibitors (bortezomib, carfilzomib or ixazomib) is able to elicit a haematological response within a few days. If there is a good haematological response to treatment, up to 50% of patients with renal failure will restore their renal function. Renal function repair can be accelerated by removing light chains from serum by dialysis with high-cutoff membrane (HCO-HD). Using this procedure can increase the chance of dialysis independence in more than 60% of patients with renal failure. Data from previously published studies on HCO-HD (MYRE or EuLITE study) have not yielded as optimistic results as originally expected, however, HCO-HD could be beneficial for some subgroup of patients with renal failure in myeloma kidney. Despite the fact that overall prognosis and survival of patients with multiple myeloma have dramatically improved, the condition with renal failure in these patients remains serious.

Keywords: bortezomib, dialysis with high-cutoff membrane, multiple myeloma, cast nephropathy, renal failure.

Published: November 3, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ryšavá R. Renal failure in multiple myeloma and its treatment. Vnitr Lek. 2020;66(7):425-431. doi: 10.36290/vnl.2020.122.
Download citation

References

  1. Tsakiris DJ, Stel VS, Finne P, et al. Incidence and outcome of patients starting renal replacement therapy for end‑stage renal disease due ti multiple myeloma or light‑chain deposition disease: an ERA‑EDTA Registry study. Nephrol Dial Transplant 2010; 25: 1200-1206. Go to original source... Go to PubMed...
  2. Knudsen LM, Hippe E, Hjorth M, et al. Renal function in newly diagnosed multiple myeloma - a demographic study of 1353 patients. The Nordic Myeloma Study Group. Eur J Haematol 1994; 53: 207-212. Go to original source... Go to PubMed...
  3. Dimopoulos MA, Terpos E, Chanan‑Khan A, 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: 4976-4984. Go to original source... Go to PubMed...
  4. Wirk B. Renal failure in multiple myeloma: a medical emergency. Bone Marrow Transplantation 2011; 46: 771-783. Go to original source... Go to PubMed...
  5. Korbet SM, Schwartz MM. Multiple myeloma. J Am Soc Nephrol 2006; 17: 2533-2545. Go to original source... Go to PubMed...
  6. Heher EC, Rennke HG, Laubach JP, et al. Kidney disease and multiple myeloma. Clin J Am Soc Nephrol 2013; 8: 2007-2017. Go to original source... Go to PubMed...
  7. Wochner RD, Strober W, Waldmann TA. The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulins fragments. J Exp Med 1967; 126: 207-221. Go to original source... Go to PubMed...
  8. Ying WZ, Wang PX, Sanders PW. Pivotal role of apoptosis signal‑regulating kinase 1 in monoclonal free light chain‑mediated apoptosis. Am J Patol 2012; 180: 41-47. Go to original source... Go to PubMed...
  9. Sengul S, Zwizinski C, Batuman V. Role of MAPK pathways in the light chain induced cytokine production in human proximal tubule cells. Am J Renal Physiol 2003; 284: F1245-F1254. Go to original source... Go to PubMed...
  10. Cockwell P, Hutchison CA. Management options for cast nephropathy in multiple myeloma. Current Opinion in Nephrology and Hypertension 2010; 19: 550-555. Go to original source... Go to PubMed...
  11. Herrera GA, Sanders PW. Paraproteinemic renal diseases that involve the tubulo‑interstitium. Contrb Nephrol 2007; 153: 105-115. Go to original source... Go to PubMed...
  12. Ryšavá R AL. amyloidosis with renal involvement. Kidney Blood Pres Res 2007; 30: 359-364. Go to original source... Go to PubMed...
  13. Zhu L, Herrera GA, Murphy‑Ullrich JE, et al. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor‑beta. Am J Pathol 1995; 147: 375-385.
  14. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21-33. Go to original source... Go to PubMed...
  15. Rajkumar SV, Dimopoulos MA, Palumbo A. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet 2014; 15: e538-e548. Go to original source... Go to PubMed...
  16. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and responce assessment of multiple myeloma. Leukemia 2009; 23: 3-9. Go to original source... Go to PubMed...
  17. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011; 364: 1046-1060. Go to original source... Go to PubMed...
  18. Hutchison CA, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammapathy and kidney disease. Nat Rev Nephrol 2009; 5: 621-627. Go to original source... Go to PubMed...
  19. Bradwell AR, Harding SJ, Fourrier NJ, et al. Assessment of monoclonal gammapathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chem 2009; 55: 1646-1655. Go to original source... Go to PubMed...
  20. Hutchison CA, Plant T, Drayson M. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BCM Nephrology 2008; 9: 11-19. Go to original source... Go to PubMed...
  21. Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum‑free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23: 215-224. Go to original source... Go to PubMed...
  22. Haubitz M, Peest D. Myeloma - new approaches to combined nephrological‑haematological management. Nephrol Dial Transplant 2006; 21: 582-590. Go to original source... Go to PubMed...
  23. Ludwig H, Drach J, Graf H, et al. Reversal of acute renal failure by bortezomib‑based chemotherapy in patients with multiple myeloma. Haematologica 2007; 92: 1411-1414. Go to original source... Go to PubMed...
  24. Kastritis E, Anagnostopoulos A, Roussou M, et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethazone‑containing regimes and tje impact of novel agents. Haematologica 2007; 92: 546-549. Go to original source... Go to PubMed...
  25. Chanan‑Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma with advanced renal failure. Blood 2007; 109: 2604-2606. Go to original source... Go to PubMed...
  26. Dimopoulos MA, Roussou M, Gavriatopoulos M, et al. Outcomes of newly diagnosed myeloma patients requiring dialysis: renal recovery, importance of rapid response and survival benefit. Blood Cancer J 2017; 7: e571. Go to original source... Go to PubMed...
  27. Clark WF, Stewart AK, Rock GA, et al. Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial. Ann Intern Med 2005; 143: 777-784. Go to original source... Go to PubMed...
  28. Leung N, Gertz MA, Zeldenrust SR. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. Kidney Int 2008; 73: 1282-12888. Go to original source... Go to PubMed...
  29. Hutchison CA, Cockwell P, Reid S, et al. Efficient removal of immunoglobulin free light chains by hemodialysis for mulitple myeleoma. In vitro and in vivo studies. J Am Soc Nephrol 2007; 18: 886-895. Go to original source... Go to PubMed...
  30. Hutchison CA, Bradwell AR, Cook M, et al. Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut‑Off Hemodialysis. Clin J Am Soc Nephrol 2009; 4: 745-754. Go to original source... Go to PubMed...
  31. Gerth HU, Pohlen M, Görlich D, et al. Impact of High‑Cut‑Off Dialysis on Renal Recovery in Dialysis‑Dependent Multiple Myeloma Patients: Results from a Case‑Control Study. Plos One 6; 11: e0154993. Go to original source...
  32. Bridoux F, Carron PL, Pegourie B, et al. Effect of high‑cutoff hemodialysis vs conventional hemodialysis on hemodialysis independence among patients with myeloma cast nephropathy. A randomized clinical trial. JAMA 2017; 318: 2099-2110. Go to original source... Go to PubMed...
  33. Hutchison CA, Cockwell P, Moroz V, et al. High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial. Lancet Haematol 2019; 6(4): e217-e228. Go to original source... Go to PubMed...
  34. Finkel K, Fabbrini P. High cut‑off hemodialysis for myeloma cast nephropathy - do we finally have an answer? J Onco‑Nephrol 2017; 1: 67-70. Go to original source...
  35. Haynes RJ, Read S, Collins GP, et al. Presentation and survival of patients with severe acute kidney injury and multiple myeloma: a 20-year experience from a single centre. Nephrol Dial Transplant 2010; 25: 419-426. Go to original source... Go to PubMed...
  36. Parikh GC, Amjad AL, Saliba RM, et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant 2009; 15: 812-816. Go to original source... Go to PubMed...
  37. Raab MS, Breitkreutz I, Hundemer M, et al. The outcome of autologous stem cell transplantation in patients with plasma cell disorders and dialysis‑dependent renal failure. Haematologica 2006; 11: 1555-1558.
  38. Caillard S, Agodoa LY, Bohen EM, et al. Myeloma, Hodgkin disease and lymphoid leukemia after renal transplantation: characteristics, risk factors and prognosis. Transplantation 2006; 81: 888-895. Go to original source... Go to PubMed...
  39. Bridoux F, Leung N, Hutchison C, et al. Diagnosis of monoclonal gammopathy of renal signifikance. Kidney Int 2015; 87: 698-711. Go to original source... Go to PubMed...
  40. Sethi S, Rajkumar SV, D'Agati VD. The complexity and heterogeneity of monoclonal immunoglobulin‑associated renal diseases. J Am Soc Nephrol 2018; 29: 1810-1823. Go to original source... Go to PubMed...




Vnitřní lékařství

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.