Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis

Abstract

Background Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. Methods A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy–induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. Results We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76–1.35], I2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71–2.45), I2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09–4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68–2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58–2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6–54.7), I2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4–79.3), I2 = 95.1%] light chain levels. Conclusion Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.

The use of medium cutoff dialyzers in patients with multiple myeloma and acute kidney injury requiring hemodialysis: A systematic review

“…16 A meta-analysis that consisted of these two RCTs and three retrospective cohort studies included 276 patients and found that HCO-HD was not associated with HD independence at 3, 6, and 12 months or mortality benefit. 11 The two RCTs may have been be underpowered to show a small but clinically significant benefit on the primary outcome because of the small number of patients recruited (98 patients in the MYRE study and 90 patients in the EuLITE study). They also had differing protocols in terms of pre-dialysis care, dialysis prescription, and chemotherapeutic regimens.…”

“…9 Although it is effective in the removal of FLC, it also leads to the removal of essential molecules including albumin (68 kDa). [9][10][11] The introduction of medium cutoff (MCO) dialyzer allows for the elimination of FLC like the HCO dialyzer, yet has the ability to retain albumin. 12 It has also been found to be safe and well tolerated as compared to high-flux HD.…”

“…On the other hand, high cutoff (HCO) HD uses a dialyzer with a large pore size (≤65 kDa) 9 . Although it is effective in the removal of FLC, it also leads to the removal of essential molecules including albumin (68 kDa) 9–11 . The introduction of medium cutoff (MCO) dialyzer allows for the elimination of FLC like the HCO dialyzer, yet has the ability to retain albumin 12 .…”

High-cutoff hemodialysis in multiple myeloma patients with acute kidney injury

“…The high clearance properties of HCO-HD versus HF-HD for FLCs and the higher hematological response at 3 months were also confirmed in a meta-analysis incorporating the results of these two RCTs and three cohort studies ( 44 , 53 , 54 ). Nevertheless, no significant difference was found between HCO-HD and HF-HD in terms of improving renal recovery outcomes ( 58 ). In another study of 83 patients with AKI secondary to MM, in which 31 patients needed dialysis, bortezomib-based triplets were associated with a high potential for kidney response ( 59 ).…”

An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment

“…A recent meta-analysis, which included data from these two randomized trials as well as from three observational studies, noted heterogeneity between study populations but found no difference in survival or renal benefits with HCO-HD versus conventional HD, though a trend toward higher dialysis independence was seen in the HCO-HD group. 24 Hemodiafiltration with ultrafiltrate regeneration offers an alternative approach to removing monoclonal FLCs and has been associated with less albumin loss than HCO-HD. 25 A small observational study 26 suggested that hemodiafiltration with ultrafiltrate regeneration may result in sustained FLC reduction with potential for renal recovery in patients with RI and MM.…”