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.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bridoux reported receiving lecture fees from Amgen, Baxter, Celgene, and Janssen. No other disclosures were reported.

Figures

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.