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

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.

Figure 1.

Simplified algorithm for evaluation of suspected paraprotein–related kidney dysfunction. Adapted from reference .

Figure 2.

Percentage of urinary protein that is albumin in the four main types of paraprotein–related kidney dysfunction. Data are shown as means. The mean percentage urinary albumin was highest in patients with amyloidosis or light–chain deposition disease (LCDD). It was lower in patients with acute tubular necrosis (ATN) and lower still in patients with cast nephropathy (CN). In this series, no patient with CN had a urinary albumin of >26%. Modified from reference , with permission.

Figure 3.

Comparison of sieving coefficients of high-flux and high-cutoff (HCO) membranes. κ-FLC, κ-free light chain. Modified from reference , with permission.