Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence Among Patients With Myeloma Cast Nephropathy: A Randomized Clinical Trial

Abstract

Importance: Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively.

Objective: To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability).

Design, setting, and participants: Randomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016.

Interventions: Intensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone.

Main outcomes and measures: Primary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death.

Results: Among 98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range, 61.2-75.3 years]; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died.

Conclusions and relevance: Among patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference.

Trial registration: clinicaltrials.gov Identifier: NCT01208818.

Figure 1.. Study Flowchart of High-Cutoff vs Conventional Hemodialysis

^aEntered another randomized study comparing 2 bortezomib-based chemotherapeutic regimens (bortezomib and dexamethasone vs bortezomib, cyclophosphamide, and dexamethasone) for kidney outcome. ^bRequired treatment with hemodialysis because of the presence of at least 1 of the following: hyperkalemia, metabolic acidosis, fluid overload, or symptoms of uremia. ^cAllows efficient serum immunoglobulin light chain removal through very large membrane pores. ^dIn accordance with the intention-to-treat principle, this patient was included in the analysis of the high-cutoff hemodialysis group.

Figure 2.. Kidney and Patient Outcomes

A, The median follow-up (until hemodialysis independence or, if not, within the 12-month observation period) was 5.1 months (interquartile range [IQR], 1.3-12.1 months) in the high-cutoff hemodialysis group and 8.0 months (IQR, 1.8-12.1 months) in the conventional hemodialysis group. After 3 months, 9 patients in the high-cutoff hemodialysis group reached hemodialysis independence compared with 2 patients in the conventional hemodialysis group. B, The short vertical bars on the curves indicate censored observations. The median duration of follow-up was 19.5 months (IQR, 12.0-30.8 months) in the high-cutoff hemodialysis group and 17.0 months (IQR, 10.9-27.5 months) in the conventional hemodialysis group.