Background: In patients with cast nephropathy and acute kidney injury (AKI) requiring dialysis, the reduction of serum free light chains (FLC) using chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may improve renal and patient outcomes. We evaluated the effectiveness of a combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate membrane (IHD-PMMA) on renal recovery and survival. Methods: A single-center retrospective cohort-study was conducted. Between 2007 and 2014, patients with dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA were included. Patients had six 6-h hemodialysis sessions a week, until predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary outcomes were renal recovery, defined as dialysis independence, and survival. Results: Seventeen patients were included, all with stage 3 AKI. All received chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the overall hematological response rate was 57%; hematological response was maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months, 76, 75, and 62% of patients were alive, respectively. Higher reduction in involved FLC by day 12 (p = 0.022) and day 21 (p = 0.003) was associated with renal recovery. Patients with FLC reduction rate >50% by day 21 experienced a lower mortality (hazard ratio 0.10, 95% CI 0.02–0.63). Conclusion: In patients with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA combined with chemotherapy was associated with high rates of renal recovery and survival.

Abbott KC, Agodoa LY: Multiple myeloma and light chain-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival. Clin Nephrol 2001; 56: 207–210.
Tsakiris DJ, Stel VS, Finne P, Fraser E, Heaf J, de Meester J, et al: Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA registry study. Nephrol Dial Transplant 2010; 25: 1200–1206.
Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al: Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21–33.
Eleutherakis-Papaiakovou V, Bamias A, Gika D, Simeonidis A, Pouli A, Anagnostopoulos A, et al: Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma 2007; 48: 337–341.
Matsue K, Fujiwara H, Iwama KI, Kimura SI, Yamakura M, Takeuchi M: Reversal of dialysis-dependent renal failure in patients with advanced multiple myeloma: single institutional experiences over 8 years. Ann Hematol 2010; 89: 291–297.
Knudsen LM, Hjorth M, Hippe E: Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 2000; 65: 175–181.
Dimopoulos MA, Sonneveld P, Leung N, Merlini G, Ludwig H, Kastritis E, et al: International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol 2016; 34: 1544–1557.
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.
Dimopoulos MA, Delimpasi S, Katodritou E, Vassou A, Kyrtsonis MC, Repousis P, et al: Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents. Ann Oncol 2014; 25: 195–200.
Uttervall K, Duru AD, Lund J, Liwing J, Gahrton G, Holmberg E, et al: The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment. PLoS One 2014; 9:e101819.
Kleber M, Ihorst G, Deschler B, Jakob C, Liebisch P, Koch B, et al: Detection of renal impairment as one specific comorbidity factor in multiple myeloma: multicenter study in 198 consecutive patients. Eur J Haematol 2009; 83: 519–527.
Haynes RJ, Read S, Collins GP, Darby SC, Winearls CG: 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.
Chanan-Khan AA, Kaufman JL, Mehta J, Richardson PG, Miller KC, Lonial S, et al: Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood 2007; 109: 2604–2606.
Dimopoulos MA, Roussou M, Gavriatopoulou M, Zagouri F, Migkou M, Matsouka C, et al: Reversibility of renal impairment in patients with multiple myeloma treated with bortezomib-based regimens: identification of predictive factors. Clin Lymphoma Myeloma 2009; 9: 302–306.
Ludwig H, Adam Z, Hajek R, Greil R, Tóthová E, Keil F, et al: Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study. J Clin Oncol 2010; 28: 4635–4641.
Morabito F, Gentile M, Ciolli S, Petrucci MT, Galimberti S, Mele G, et al: Safety and efficacy of bortezomib-based regimens for multiple myeloma patients with renal impairment: a retrospective study of Italian Myeloma Network GIMEMA. Eur J Haematol 2010; 84: 223–228.
Dimopoulos MA, Kastritis E, Rosinol L, Bladé J, Ludwig H: Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 2008; 22: 1485–1493.
Wochner RD, Strober W, Waldmann TA: The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments. J Exp Med 1967; 126: 207–221.
Waldmann TA, Strober W, Mogielnicki RP: The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 1972; 51: 2162–2174.
Hutchison CA, Bradwell AR, Cook M, Basnayake K, Basu S, Harding S, 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.
Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, et al: Early reduction of serum-free light chains associates with renal recovery in myeloma kidney. J Am Soc Nephrol 2011; 22: 1129–1136.
Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, et al: Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol 2007; 18: 886–895.
Bonomini M, Fiederling B, Bucciarelli T, Manfrini V, Di Ilio C, Albertazzi A: A new polymethylmethacrylate membrane for hemodialysis. Int J Artif Organs 1996; 19: 232–239.
Galli F, Benedetti S, Floridi A, Canestrari F, Piroddi M, Buoncristiani E, et al: Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers. Kidney Int 2005; 67: 750–759.
Wennekers AB, Azara PM, Sahun VD, Liberal BB, Laiglesia JE, Perna PV, et al: Thirteen treated of acute renal failure secondary to multiple myeloma with high cut off filters. Nefrologia 2016; 36: 418–426.
Ricci Z, Cruz DN, Ronco C: Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria. Nat Rev Nephrol 2011; 7: 201–208.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.
Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al: International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.
Clark WF, Stewart AK, Rock GA, Sternbach M, Sutton DM, Barrett BJ, et al: Plasma exchange when myeloma presents as acute renal failure: a randomized, controlled trial. Ann Intern Med 2005; 143: 777–784.
Yu X, Gan L, Wang Z, Dong B, Chen X: Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis. Int J Clin Pharmacol Ther 2015; 53: 391–397.
Hutchison CA, Heyne N, Airia P, Schindler R, Zickler D, Cook M, et al: Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis. Nephrol Dial Transplant 2012; 27: 3823–3828.
Heyne N, Denecke B, Guthoff M, Oehrlein K, Kanz L, Häring HU, et al: Extracorporeal light chain elimination: high cut-off (HCO) hemodialysis parallel to chemotherapy allows for a high proportion of renal recovery in multiple myeloma patients with dialysis-dependent acute kidney injury. Ann Hematol 2012; 91: 729–735.
Zannetti BA, Zamagni E, Santostefano M, De Sanctis LB, Tacchetti P, Mancini E, et al: Bortezomib-based therapy combined with high cut-off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment. Am J Hematol 2015; 90: 647–652.
Gerth HU, Pohlen M, Görlich D, Thölking G, Kropff M, Berdel WE, 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:e0154993.
Hutchison CA, Cook M, Heyne N, Weisel K, Billingham L, Bradwell A, et al: European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): a randomised control trial. Trials 2008; 9: 55.
Bridoux F, Fermand JP: Optimizing treatment strategies in myeloma cast nephropathy: rationale for a randomized prospective trial. Adv Chronic Kidney Dis 2012; 19: 333–341.
Hutchison CA, Cockwell P, Heyne N, Weisel KC, Fifer LB, Gillmore JD, et al: European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): survival and renal outcomes. J Am Soc Nephrol 2016; 27: 8A.
Bridoux F, Carron PL, Alamartine E, Peraldi MN, Karras A, Vigneau C, et al: Treatment of myeloma cast nephropathy: a randomized trial comparing intensive hemodialysis with high cutoff or standard high-flux dialyzers (the MYRE study). J Am Soc Nephrol 2016; 27: 8A.
Fabbrini P, Sirtori S, Casiraghi E, Pieruzzi F, Genovesi S, Corti D, et al: Polymethylmethacrylate membrane and serum free light chain removal: enhancing adsorption properties. Blood Purif 2013; 35(suppl 2):52–58.
Dimopoulos MA, Roussou M, Gkotzamanidou M, Nikitas N, Psimenou E, Mparmparoussi D, et al: The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia 2013; 27: 423–429.
Dimopoulos MA, Richardson PG, Schlag R, Khuageva NK, Shpilberg O, Kastritis E, et al: VMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impaired renal function, and results in reversal of renal impairment: cohort analysis of the phase III VISTA study. J Clin Oncol 2009; 27: 6086–6093.
Jagannath S, Barlogie B, Berenson JR, Singhal S, Alexanian R, Srkalovic G, et al: Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal function. Cancer 2005; 103: 1195–1200.
San-Miguel JF, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, et al: Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study. Leukemia 2008; 22: 842–849.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.