Paraprotein-Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy

Clin J Am Soc Nephrol. 2016 Dec 7;11(12):2273-2279. doi: 10.2215/CJN.01640216. Epub 2016 Aug 15.

Abstract

Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm-Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high-cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high-cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.

Keywords: HCO dialysis; Humans; Immunoglobulin Light Chains; Molecular Weight; Myeloma Proteins; Plasma Exchange; Randomized Controlled Trials as Topic; Standard of Care; Uromodulin; acute renal failure; cast nephropathy; free light chains; multiple myeloma; multiple myeloma M-proteins; renal dialysis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Immunoglobulin Light Chains / metabolism
  • Kidney Diseases / diagnosis
  • Kidney Diseases / etiology*
  • Kidney Diseases / therapy*
  • Multiple Myeloma / complications*
  • Multiple Myeloma / therapy*
  • Plasma Exchange
  • Renal Dialysis / methods
  • Stem Cell Transplantation
  • Uromodulin / metabolism

Substances

  • Antineoplastic Agents
  • Immunoglobulin Light Chains
  • UMOD protein, human
  • Uromodulin