Expanded hemodialysis in the treatment of patients with multiple myeloma

Aim: myeloma cast nephropathy is one of the most serious complications in the course of multiple myeloma (MM), worsening the life prognosis significantly. Since the development of AKI in MM is associated with the production of free light chains (FLC), a decrease in its concentration using extracorporeal techniques can provide a positive effect in the course of the disease. Recently, more and more studies have demonstrated the significant efficiency of the new expanded HD (HDx) technique in removing substances of average molecular weight, but there are only a few studies of the effect of using this technique in the treatment of patients with MM. The aim of this study was to evaluate the effectiveness of HDx technique in FLC removal in comparison with conventional HD (сHD) and high-flow HDF. Method: The study included patients with myeloma nephropathy AKI and indications for an emergency HD start. Each patient underwent sequential procedures: cHD, HDF and HDx. Before the start of the treatment and every 30 minutes during the procedures, the concentration of FLC (kappa and lambda), b-2-microglobulin (β2M), and serum albumin was determined. Results: the study included 7 patients, with a mean age of 68±8 years. In contrast to cHD, a significant decrease in β2M concentration by the end of the procedure was observed both with HDF (by an average of 49±12%, p<0.001) and with HDx (by an average of 59±6%, p<0.001). There was also a significant decrease in the kappa FLC concentration (HDF - 35±34%, p<0.05; HDx - 32±12%, p<0.001) and lambda FLC (HDF - 40±20%, p<0.01; HDx - 31±21%, p<0.05). With сHD, the FLC concentration did not change. There were no significant differences in β2M and FLC concentration decrease between HDF and HDx. None of the techniques resulted in a decrease in serum albumin levels. Conclusion: the HDx technique in patients with MM contributes to a significant decrease in the level of β2M and FLC and does not lead to albumin loss.

миелома, миеломная нефропатия, ОПП, расширенный гемодиализ, онконефрология, свободные легкие цепи, плазмаклеточные дискразии, myeloma, myeloma nephropathy, AKI, Expanded hemodialysis, onconephrology, free light chains, plasma cell dyscrasias

1. Менделеева Л.П., Вотякова О.М., Рехтина И.Г. Множественная миелома. Российские клинические рекомендации по диагностике и лечению злокачественных лимфопролиферативных заболеваний; под ред. И.В. Поддубной, В.Г. Савченко. Москва, 2018. C. 213-241.

2. Kyle R.A., Rajkumar S.V. Multiple myeloma. N Engl J Med. 2004; 351(18): 1860-73. doi: 10.1056/NEJMra041875.

3. Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016; 43(6): 676-681. doi: 10.1053/j.seminoncol.2016.11.004.

4. Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018. 250 c.

5. Росстат. Демографические данные 2020 г. Число умерших по причинам смерти.

6. Altekruse S.F., Kosary C.L., Krapcho M. et al. SEER cancer statistics review, 1975- 2007. Bethesda, MD: National Cancer Institute, based on November 2009 SEER data submission, posted to the SEER, 2010. https://seer.cancer.gov/archive/csr/1975_2007/

7. Kristinsson S.Y., Landgren O., Dickman P.W. et al. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007; 25(15): 1993-9. doi: 10.1200/JCO.2006.09.0100.

8. Cowan A.J., Allen C., Barac A. et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018; 4(9): 1221-1227. doi: 10.1001/jamaoncol.2018.2128

9. Kumar S.K., Rajkumar S.V., Dispenzieri A. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008; 111(5): 2516-20. doi: 10.1182/blood-2007-10-116129.

10. Andronesi A.G., Tanase A.D., Sorohan B.M. et al. Incidence and risk factors for acute kidney injury following autologous stem cell transplantation for multiple myeloma. Cancer Med. 2019; 8(6): 3278-3285. doi: 10.1002/cam4.2187.

11. Dhakal B., Szabo A., Chhabra S. et al. Autologous Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction: A Systematic Review and Meta-analysis. JAMA Oncol. 2018; 4(3): 343-350. doi: 10.1001/jamaoncol.2017.4600.

12. Kumar S.K., Dingli D., Lacy M.Q. et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: Results from a matched pair analysis. Am J Hematol. 2008; 83(8): 614-7. doi: 10.1002/ajh.21191.

13. Bashir Q., Shah N., Parmar S. et al. Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥70 years with multiple myeloma. Leuk Lymphoma. 2012; 53(1): 118-22. doi: 10.3109/10428194.2011.606942.

14. Kyle R.A., Gertz M.A., Witzig T.E. et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78(1): 21-33. doi: 10.4065/78.1.21.

15. Dimopoulos M.A., Kastritis E., Rosinol L. et al. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008; 22(8): 1485-93. doi: 10.1038/leu.2008.131.

16. Bladé J., Sonneveld P., San Miguel JF et al. Pegylated liposomal doxorubicin plus bortezomib in relapsed or refractory multiple myeloma: efficacy and safety in patients with renal function impairment. Clin Lymphoma Myeloma. 2008 Dec; 8(6):3 52-5. doi: 10.3816/CLM.2008.n.051.

17. Tariman, J., & Faiman, B. Multiple myeloma. In C.H. Yarbro, D. Wujcik, & B.H. Gobel (Eds.), Cancer nursing: Principles and practice (7th ed., pp. 1513-1545). Boston, MA: Jones and Bartlett, 2011.

18. Takano J., Mine S., Mochizuki M. et al. Late-stage myeloma invades kidney without significant effect on renal function: findings from 53 autopsies in a single institute. Int J Hematol. 2019; 109(2): 147-153. doi:10.1007/s12185-018-2546-8.

19. Khan R., Apewokin S., Grazziutti M. et al. Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma. Leukemia. 2015; 29(5): 1195-201. doi: 10.1038/leu.2015.15.

20. Antlanger M., Reiter T., Lamm W. et al. Does renal failure affect outcome after autologous stem cell transplantation in patients with multiple myeloma? Blood. 2016; 128:4642.

21. Kumar S.K., Rajkumar V., Kyle R.A. et al. Multiple myeloma. Nat Rev Dis Primers. 2017; 3: 17046. doi: 10.1038/nrdp.2017.46.

22. Solomon A. Light chains of human immunoglobulins. Methods Enzymol. 1985; 116: 101-21. doi: 10.1016/s0076-6879(85)16008-8.

23. Sanders P.W. Mechanisms of light chain injury along the tubular nephron. J Am Soc Nephrol. 2012; 23(11): 1777-81. doi: 10.1681/ASN.2012040388.

24. Hutchison C.A., Harding S., Hewins P. et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2008; 3(6): 1684-90. doi: 10.2215/CJN.02290508.

25. Haynes R., Hutchison C.A., Emberson J. et al. Serum free light chains and the risk of ESRD and death in CKD. Clin J Am Soc Nephrol. 2011; 6(12): 2829-37. doi: 10.2215/CJN.03350411.

26. Desjardins L., Liabeuf S., Lenglet A. et al. Association between free light chain levels, and disease progression and mortality in chronic kidney disease. Toxins (Basel). 2013; 5(11): 2058-73. doi: 10.3390/toxins5112058.

27. Hutchison C.A., Cockwell P., Stringer S. et al. Early reduction of serum-free light chains associates with renal recovery in myeloma kidney. J Am Soc Nephrol. 2011; 22(6): 1129-36. doi: 10.1681/ASN.2010080857.

28. Clark W.F., Stewart A.K., Rock G.A. et al. Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial. Ann Intern Med. 2005; 143(11): 777-84. doi: 10.7326/0003-4819-143-11-200512060-00005.

29. Yu X., Gan L., Wang Z. et al. Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis. Int J Clin Pharmacol Ther. 2015; 53(5): 391-7. doi: 10.5414/CP202245.

30. Kawabe M., Yamamoto I., Katsuma A. et al. Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange. CEN Case Rep. 2016; 5(2): 232-237. doi: 10.1007/s13730-016-0231-4.

31. Hutchison C.A., Bradwell A.R., 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(4): 745-54. doi: 10.2215/CJN.04590908.

32. Gerth H.U., 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. 2016; 11(5): e0154993. doi: 10.1371/journal.pone.0154993.

33. Sáez M.I., Camarero V., Rosales A. et al. Acute renal failure in patients with myeloma: Experience with extended high cut-off hemodialysis. Nefrologia. 2017; 37(4): 429-431. English, Spanish. doi: 10.1016/j.nefro.2016.10.014.

34. Hutchison C.A., 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. doi: 10.1016/S2352-3026(19)30014-6.

35. Steiner N., Abdel Hamid A., Kronbichler A. et al. Real world analysis of high-cut-off (HCO) hemodialysis with bortezomib-based backbone therapy in patients with multiple myeloma and acute kidney injury. J Nephrol. 2021; 34(4): 1263-1270. doi:10.1007/s40620-020-00939-2.

36. Sallée M., Burtey S. Myeloma cast nephropathy: the dusk of high cutoff haemodialysis. Lancet Haematol. 2019; 6(4): e174-e176. doi: 10.1016/S2352-3026(19)30044-4.

37. Lamy T., Henri P., Lobbedez T. et al. Comparison between on-line high-efficiency hemodiafiltration and conventional high-flux hemodialysis for polyclonal free light chain removal. Blood Purif. 2014; 37(2): 93-8. doi: 10.1159/000357968.

38. Granger Vallée A., Chenine L., Leray-Moragues H. et al. Online high-efficiency haemodiafiltration achieves higher serum free light chain removal than high-flux haemodialysis in multiple myeloma patients: preliminary quantitative study. Nephrol Dial Transplant. 2011; 26(11): 3627-33. doi: 10.1093/ndt/gfr180.

39. Sens F., Chaintreuil D., Jolivot A et al. Effectiveness of IHD with Adsorptive PMMA Membrane in Myeloma Cast Nephropathy: A Cohort Study. Am J Nephrol. 2017; 46(5): 355-363. doi: 10.1159/000481461.

40. Ciceri P., Cozzolino M. Expanded Haemodialysis as a Current Strategy to Remove Uremic Toxins. Toxins (Basel). 2021; 13(6): 380. doi: 10.3390/toxins13060380.

41. Cozzolino M., Magagnoli L., Ciceri P. et al. Effects of a medium cut-off (Theranova®) dialyser on haemodialysis patients: a prospective, cross-over study. Clin Kidney J. 2019; 14(1): 382-389. doi: 10.1093/ckj/sfz155.

42. Zickler D., Schindler R., Willy K. et al. Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial. PLoS One. 2017; 12(1): e0169024. doi: 10.1371/journal.pone.0169024.

43. Belmouaz M., Bauwens M., Hauet T. et al. Comparison of the removal of uraemic toxins with medium cut-off and high-flux dialysers: a randomized clinical trial. Nephrol Dial Transplant. 2020; 35(2): 328-335. doi: 10.1093/ndt/gfz189.

44. Krishnasamy R., Hawley C.M., Jardine M.J. et al. A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study. Blood Purif. 2020; 49(4): 468-478. doi: 10.1159/000505567.

45. Kirsch A.H., Lyko R., Nilsson L.G. et al. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017; 32(1): 165-172. doi: 10.1093/ndt/gfw310. Erratum in: Nephrol Dial Transplant. 2021; 36(8): 1555-1556.

46. Kim T.H., Kim S.H., Kim T.Y. et al. Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study. BMC Nephrol. 2019; 21(1): 2. doi: 10.1186/s12882-019-1669-3.

47. Cazorla López J.M., García García-Doncel A., Naranjo Muñoz J. et al. Experience of using hemodialysis with medium cut-off dialyzer in cast nephropathy. Nefrologia (Engl Ed). 2020; 40(3): 367-369. English, Spanish. doi: 10.1016/j.nefro.2019.09.008.

48. Румянцев А.Ш. Инновации в гемодиализе. Нефрология и диализ. 2019. 21(2): 199-212. doi: 10.28996/2618-9801-2019-2-199-212.

49. Florens N., Juillard L. Expanded haemodialysis: news from the field. Nephrol Dial Transplant. 2018; 33(suppl_3):iii48-iii52. doi: 10.1093/ndt/gfy203.

50. European Best Practice Guidelines for Haemodialysis II.2 Haemodialysis dose quantification: middle molecules. Nephrol Dial Transplant. 2002; 17, Suppl. 7: 21-23. doi: 10.1093/ndt/17.suppl_7.21.

51. Wizemann V., Lotz C., Techert F., Uthoff S. On-line haemodiafiltration versus low-flux haemodialysis. A prospective randomized study. Nephrol Dial Transplant. 2000; 15 Suppl 1: 43-8. doi: 10.1093/oxfordjournals.ndt.a027963.

52. Wang R., Hu H., Hu S. et al. β2-microglobulin is an independent indicator of acute kidney injury and outcomes in patients with intracerebral hemorrhage. Medicine (Baltimore). 2020; 99(8): e19212. doi: 10.1097/MD.0000000000019212.

53. Astor B.C., Muth B., Kaufman D.B. et al. Serum β2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation. Kidney Int. 2013; 84(4): 810-7. doi: 10.1038/ki.2013.172.

54. Foster M.C., Coresh J., Hsu C.Y. et al. Serum β-Trace Protein and β2-Microglobulin as Predictors of ESRD, Mortality, and Cardiovascular Disease in Adults With CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2016; 68(1): 68-76. doi: 10.1053/j.ajkd.2016.01.015.

55. Astor B.C., Shafi T., Hoogeveen R.C. et al. Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population. Am J Kidney Dis. 2012; 59(5): 653-62. doi: 10.1053/j.ajkd.2011.11.042.

56. Sanchez E., Li M., Kitto A. et al. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012; 158(6): 727-38. doi: 10.1111/j.1365-2141.2012.09241.x.

57. Greipp P.R., San Miguel J., Durie B.G. et al. International staging system for multiple myeloma. J Clin Oncol. 2005; 23(15): 3412-20. doi: 10.1200/JCO.2005.04.242.