Dataset Information

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.

SUBMITTER: Bridoux F

PROVIDER: S-EPMC5820717 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAcute 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.MethodsA 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.ResultsWe 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], I 2 = 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), I 2 = 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), I 2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4-79.3), I 2 = 95.1%] light chain levels.ConclusionCurrent 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.

Project description:BackgroundPhysical and emotional symptoms are prevalent in patients with kidney-dysfunction requiring dialysis (KDRD) and the rigors of thrice-weekly hemodialysis (HD) may contribute to deteriorated health-related quality of life. Less intensive HD schedules might be associated with lower symptom and/or emotional burden.MethodsThe TWOPLUS Pilot study was an individually-randomized trial conducted at 14 dialysis units, with the primary goal to assess feasibility and safety. Patients with incident KDRD and residual kidney function were assigned to incremental HD start (twice-weekly HD for 6 weeks followed by thrice-weekly HD) vs conventional HD (thrice-weekly HD). In exploratory analyses, we compared the two treatment groups with respect to three patient-reported outcomes measures. We analyzed the change from baseline in the score on Dialysis Symptom Index (DSI, range 0-150), Generalized Anxiety Disorder-7 (GAD-7, range 0-21), and Patient Health Questionnaire-9 (PHQ-9, range 0-27) at 6 (n = 20 in each treatment group) and 12 weeks (n = 21); with lower scores denoting lower symptom burden. Analyses were adjusted for age, race, gender, baseline urine volume, diabetes mellitus, and malignancy. Participants' views on the intervention were sought using a Patient Feedback Questionnaire (n = 14 in incremental and n = 15 in conventional group).ResultsThe change from baseline to week 6 in estimated mean score (standard error; P value) in the incremental and conventional group was - 9.7 (4.8; P = 0.05) and - 13.8 (5.0; P = 0.009) for DSI; - 1.9 (1.0; P = 0.07) and - 1.5 (1.4; P = 0.31) for GAD-7; and - 2.5 (1.1; P = 0.03) and - 3.5 (1.5; P = 0.02) for PHQ-9, respectively. Corresponding changes from week 6 to week 12 were - 3.1 (3.2; P = 0.34) and - 2.4 (5.5; P = 0.67) in DSI score; 0.5 (0.6; P = 0.46) and 0.1 (0.6; P = 0.87) in GAD-7 score; and - 0.3 (0.6; P = 0.70) and - 0.5 (0.6; P = 0.47) in PHQ-9 score, respectively. Majority of respondents felt their healthcare was not jeopardized and expressed their motivation for study participation was to help advance the care of patients with KDRD.ConclusionsThis study suggests a possible mitigating effect of twice-weekly HD start on symptoms of anxiety and depression at transition from pre-dialysis to KDRD. Larger clinical trials are required to rigorously test clinically-matched incrementally-prescribed HD across diverse organizations and patient populations.Trial registrationRegistered at ClinicalTrials.gov with study identifier NCT03740048, registration date 14/11/2018.

Project description:IntroductionIn cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF).MethodsIn a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration.ResultsThere were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181).ConclusionTherefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.