Treatment of kidney disease in multiple myeloma
- S Vincent Rajkumar, MD
S Vincent Rajkumar, MD
- Edward W. and Betty Knight Scripps Professor of Medicine
- Mayo Clinic
- Andre A Kaplan, MD
Andre A Kaplan, MD
- Professor of Medicine
- University of Connecticut Health Center
- Nelson Leung, MD
Nelson Leung, MD
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
Kidney injury is a relatively common problem in patients with multiple myeloma . Renal disease most often occurs in patients with a high tumor burden  and can evolve as either an acute or chronic disorder.
Multiple etiologies have been attributed to acute kidney injury (AKI) in patients with multiple myeloma. Hypercalcemia, volume depletion, hyperuricemia, hyperviscosity (rare), and toxicity due to intravenous radiocontrast media, nonsteroidal anti-inflammatory agents (NSAIDs), or angiotensin-converting enzyme (ACE) inhibitors or receptor blockers (ARBs) all may contribute [2-6].
Myeloma cast nephropathy occurs most often in patients with high rates of production and excretion of immunoglobulin free light chains, which may be toxic to the tubules and form obstructing tubular casts, particularly if the patient is volume depleted . Other common renal lesions include primary amyloidosis or light chain deposition disease (LCDD) [2,7]. Concurrent presence of both myeloma cast nephropathy and either amyloidosis or LCDD can occur but is unusual [7-9].
Patients with amyloidosis or LCDD may not have significantly reduced kidney function at the time of presentation (although renal failure may occur if amyloidosis or LCDD is not recognized and is left untreated) and are treated with chemotherapy directed against the abnormal plasma cell clone. One of these two disorders should be suspected when there are signs of the nephrotic syndrome, including heavy albuminuria, hypoalbuminemia, and edema . Renal vein thrombosis may rarely be present in patients with nephrotic syndrome, although its contribution to renal failure in multiple myeloma is not well described. The treatment of hypercoagulability associated with the nephrotic syndrome is discussed separately. (See "Renal vein thrombosis and hypercoagulable state in nephrotic syndrome".)
This topic review will discuss the treatment of typical causes of renal failure in patients with multiple myeloma, with a focus on myeloma cast nephropathy. The types of renal disease in multiple myeloma, the pathogenesis of myeloma cast nephropathy, amyloidosis and light and heavy chain deposition diseases, and the treatment of multiple myeloma are discussed separately. (See "Types of renal disease in multiple myeloma" and "Pathogenesis and diagnosis of light chain cast nephropathy (myeloma kidney)" and "Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases" and "Overview of the management of multiple myeloma".)
- Bladé J, Fernández-Llama P, Bosch F, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med 1998; 158:1889.
- Winearls CG. Acute myeloma kidney. Kidney Int 1995; 48:1347.
- Rota S, Mougenot B, Baudouin B, et al. Multiple myeloma and severe renal failure: a clinicopathologic study of outcome and prognosis in 34 patients. Medicine (Baltimore) 1987; 66:126.
- Sanders PW, Booker BB. Pathobiology of cast nephropathy from human Bence Jones proteins. J Clin Invest 1992; 89:630.
- Cohen DJ, Sherman WH, Osserman EF, Appel GB. Acute renal failure in patients with multiple myeloma. Am J Med 1984; 76:247.
- Uchida M, Kamata K, Okubo M. Renal dysfunction in multiple myeloma. Intern Med 1995; 34:364.
- Hill GS, Morel-Maroger L, Méry JP, et al. Renal lesions in multiple myeloma: their relationship to associated protein abnormalities. Am J Kidney Dis 1983; 2:423.
- Buxbaum JN, Chuba JV, Hellman GC, et al. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med 1990; 112:455.
- Lorenz EC, Sethi S, Poshusta TL, et al. Renal failure due to combined cast nephropathy, amyloidosis and light-chain deposition disease. Nephrol Dial Transplant 2010; 25:1340.
- Leung N, Gertz M, Kyle RA, et al. Urinary albumin excretion patterns of patients with cast nephropathy and other monoclonal gammopathy-related kidney diseases. Clin J Am Soc Nephrol 2012; 7:1964.
- Zucchelli P, Pasquali S, Cagnoli L, Ferrari G. Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney Int 1988; 33:1175.
- Misiani R, Tiraboschi G, Mingardi G, Mecca G. Management of myeloma kidney: an anti-light-chain approach. Am J Kidney Dis 1987; 10:28.
- Johnson WJ, Kyle RA, Pineda AA, et al. Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy. Arch Intern Med 1990; 150:863.
- Ludwig H, Adam Z, Hajek R, 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.
- Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 2012; 30:2946.
- Ballester OF, Tummala R, Janssen WE, et al. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency. Bone Marrow Transplant 1997; 20:653.
- Ross JR, Saunders Y, Edmonds PM, et al. A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess 2004; 8:1.
- Li EC, Davis LE. Zoledronic acid: a new parenteral bisphosphonate. Clin Ther 2003; 25:2669.
- Munier A, Gras V, Andrejak M, et al. Zoledronic Acid and renal toxicity: data from French adverse effect reporting database. Ann Pharmacother 2005; 39:1194.
- Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Intern Med 1990; 150:1693.
- Kaplan AA. Therapeutic apheresis for the renal complications of multiple myeloma and the dysglobulinemias. Ther Apher 2001; 5:171.
- Durie BG, Kyle RA, Belch A, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003; 4:379.
- 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.
- Cserti C, Haspel R, Stowell C, Dzik W. Light-chain removal by plasmapheresis in myeloma-associated renal failure. Transfusion 2007; 47:511.
- Gertz MA. Managing myeloma kidney. Ann Intern Med 2005; 143:835.
- Leung N. Plasma exchange in multiple myeloma. Ann Intern Med 2006; 144:455; author reply 455.
- Leung N, Gertz MA, Zeldenrust SR, et al. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. Kidney Int 2008; 73:1282.
- Clark WF, Garg AX. Plasma exchange for myeloma kidney: cast(s) away? Kidney Int 2008; 73:1211.
- Burnette BL, Leung N, Rajkumar SV. Renal improvement in myeloma with bortezomib plus plasma exchange. N Engl J Med 2011; 364:2365.
- 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.
- Leung N, Lager DJ, Gertz MA, et al. Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis 2004; 43:147.
- Hutchison CA, 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; 22:1129.
- Russell JA, Fitzharris BM, Corringham R, et al. Plasma exchange v peritoneal dialysis for removing Bence Jones protein. Br Med J 1978; 2:1397.
- Hutchison CA, Cockwell P, Reid S, 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.
- 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.
- Chow CC, Mo KL, Chan CK, et al. Renal impairment in patients with multiple myeloma. Hong Kong Med J 2003; 9:78.
- Iggo N, Palmer AB, Severn A, et al. Chronic dialysis in patients with multiple myeloma and renal failure: a worthwhile treatment. Q J Med 1989; 73:903.
- Korzets A, Tam F, Russell G, et al. The role of continuous ambulatory peritoneal dialysis in end-stage renal failure due to multiple myeloma. Am J Kidney Dis 1990; 16:216.
- Torra R, Bladé J, Cases A, et al. Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases. Br J Haematol 1995; 91:854.
- Sharland A, Snowdon L, Joshua DE, et al. Hemodialysis: an appropriate therapy in myeloma-induced renal failure. Am J Kidney Dis 1997; 30:786.
- Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001; 114:822.
- Dagher F, Sammett D, Abbi R, et al. Renal transplantation in multiple myeloma. Case report and review of the literature. Transplantation 1996; 62:1577.
- Heher EC, Spitzer TR, Goes NB. Light chains: heavy burden in kidney transplantation. Transplantation 2009; 87:947.
- Heher EC, Spitzer TR. Hematopoietic stem cell transplantation in patients with chronic kidney disease. Semin Nephrol 2010; 30:602.
- Holland MD, Galla JH, Sanders PW, Luke RG. Effect of urinary pH and diatrizoate on Bence Jones protein nephrotoxicity in the rat. Kidney Int 1985; 27:46.
- Larsen JT, Kumar SK, Dispenzieri A, et al. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 2013; 27:941.
- Dispenzieri A, Stewart AK, Chanan-Khan A, et al. Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 2013; 122:4172.
- Kastritis E, Terpos E, Moulopoulos L, et al. Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia 2013; 27:947.
- Ying WZ, Allen CE, Curtis LM, et al. Mechanism and prevention of acute kidney injury from cast nephropathy in a rodent model. J Clin Invest 2012; 122:1777.
- ACUTE KIDNEY INJURY
- Management strategy
- - Myeloma cast nephropathy
- - Volume depletion, hypercalcemia, and hyperuricemia
- - Hypercalcemia
- - Hyperuricemia
- - Drugs with renal toxicity
- - Indications for plasmapheresis
- - Plasmapheresis protocol
- High-cutoff dialyzer
- Gauging the treatment response
- CHRONIC KIDNEY DISEASE
- End-stage renal disease
- Kidney transplantation
- Future directions
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS