High Cut-off Dialysis Research Articles

Treatment of Myeloma Cast Nephropathy (MCN): A Randomized Trial Comparing Intensive Haemodialysis (HD) with High Cut-Off (HCO) or Standard High-Flux Dialyzer in Patients Receiving a Bortezomib-Based Regimen (the MYRE Study, by the Intergroupe Francophone du Myélome (IFM) and the French Society of Nephrology (SFNDT))

▪Multiple myeloma (MM) is often revealed by acute kidney injury (AKI) usually related to MCN. Recovery of renal function is a key prognostic factor. With novel anti-myeloma agents, HD-independence occurs in about 30% of pts with severe AKI, advocating for the use of additional strategies to rapidly remove circulating monoclonal free light chains (FLC).We designed a prospective randomized trial to compare the HD-independence rate in pts with inaugural severe AKI secondary to biopsy-proven MCN, treated by intensive HD (8 sessions over the first 10 days, then thrice a week) using either a HCO dialyzer or a conventional high-flux dialyzer. In both groups, pts received 21-day courses of Bortezomib and dexamethasone (BD), reinforced by cyclophosphamide after 3 cycles in the absence of haematological response (HR).Between 2011 and 2015, 98 pts were randomised. One pt withdrew consent, and 3 had main exclusion criteria. Baseline characteristics in the control arm (n=48) and HCO arm (n=46) were close, including similarly high serum FLC levels (median 6,015mg/L).HD independence was achieved in 33% and 43% (p= 0.31) at 3 and in 37.5% and 60 % (p=0.03) at 6 mo, in the control and HCO arms, respectively. HR rate of very good partial response or above at 3 mo based on FLC was 48% in control and 59% in HCO groups (p=0.29). Tolerance of HD schedule and of chemotherapy was acceptable in both arms. At 12 mo, 17 pts have died (10 vs 7).This randomized trial demonstrates that in MM patients with MCN and severe AKI treated with a bortezomib-based regimen, intensive HCO-HD results in higher renal recovery rate than HD with conventional high-flux dialyzers. DisclosuresAugeul-Meunier:janssen: Consultancy; gilead: Consultancy. Benboubker:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

High cut-off dialysis in chronic haemodialysis patients reduces serum procalcific activity

Vascular calcification is enhanced in chronic dialysis patients, possibly due to the insufficient removal of various intermediate molecular weight uraemic toxins such as interleukins with conventional membranes. In this study, we assessed the modulation of in vitro vascular calcification with the use of high cut-off (HCO) membranes in chronic dialysis patients. In a PERCI trial, 43 chronic dialysis patients were treated with conventional high-flux and HCO filters for 3 weeks in a randomized order following a 2-period crossover design. After each phase, serum predialysis samples were drawn. Calcifying human coronary vascular smooth muscle cells (VSMCs) were incubated with the patient's serum samples. Calcification was assessed with alkaline phosphatase (ALP) and alizarin red staining. In the clinical trial, HCO dialysis reduced the serum levels of the soluble tumour necrosis factor receptor (sTNFR) 1 and 2, vascular cell adhesion molecule 1 (VCAM-1) and soluble interleukin-2 receptor (sIL2R). We therefore investigated the in vitro effects of these mediators on vascular calcification. VSMCs incubated with HCO dialysis serum showed a 26% reduction of ALP with HCO serum compared with high-flux serum. Alizarin was 43% lower after incubation with the HCO serum compared with the high-flux serum. While sIL2R and sTNFR 1 and 2 showed no effects on VSMC calcification, VCAM-1 caused a dose-dependent enhancement of calcification. The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.

High cut-off dialysis in chronic haemodialysis patients.

Haemodialysis patients suffer from chronic systemic inflammation and high incidence of cardiovascular disease. One cause for this may be the failure of diseased kidneys to eliminate immune mediators. Current haemodialysis treatment achieves insufficient elimination of proteins in the molecular weight range 15-45kD. Thus, high cut-off dialysis might improve the inflammatory state. In this randomized crossover trial, 43 haemodialysis patients were treated for 3weeks with high cut-off or high-flux dialysis. Inflammatory plasma mediators, monocyte subpopulation distribution and leucocyte gene expression were quantified. High cut-off dialysis supplemented by a low-flux filter did not influence the primary end-point, expression density of CD162 on monocytes. Nevertheless, treatment reduced multiple immune mediators in plasma. Such reduction proved - at least for some markers - to be a sustained effect over the interdialytic interval. Thus, for example, soluble TNF-receptor 1 concentration predialysis was reduced from median 13·3 (IQR 8·9-17·2) to 9·7 (IQR 7·5-13·2) ng/mL with high cut-off while remaining constant with high-flux treatment. The expression profile of multiple proinflammatory genes in leucocytes was significantly dampened. Treatment was well tolerated although albumin losses in high cut-off dialysis would be prohibitive against long-term use. The study shows for the first time that a dampening effect of high cut-off dialysis on systemic inflammation is achievable. Earlier studies had failed due to short study duration or insufficient dialysis efficacy. Removal of soluble mediators from the circulation influences cellular activation levels in leucocytes. Continued development of less albumin leaky membranes with similar cytokine elimination is justified.

Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy

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.

Treatment of amitriptyline intoxications by extended high cut-off dialysis.

Antidepressants, especially amitriptyline, are among the most frequent drug classes involved in intoxications. Despite its small molecular weight, amitriptyline is not considered to be eliminated by extracorporeal treatment methods due to its high protein binding and large volume of distribution. New high cut-off dialysers have so far not been used for removal of amitriptyline. We report two cases of amitriptyline poisoning in which we measured the amitriptyline elimination using extended high cut-off (HCO) dialysis. Despite dialyser clearances of 33 and 58 mL/min, resulting in the reduction of initial serum concentrations by ∼30%, only 211 and 920 µg of amitryptilin, respectively, (<3% of the ingested amount) could be recovered in the total collected dialysate. Hence, due to the high volume of distribution of amitriptyline, even HCO dialysis does not contribute substantially to the extracorporeal removal of amitryptilin.

Hemodialysis Using High Cut Off Filters in Light Chain Cast Nephropathy

Background/Aim: Hemodialysis using high cutoff (HCO) filters possibly improves renal function in diseases with light chain (LC) overproduction and acute kidney injury. We established the effect of HCO dialysis on renal outcome in consecutive patients with malignant monoclonal gammopathies and LC cast nephropathy. Methods: LC concentration was measured before and after each dialysis session in 10 patients receiving HCO dialysis and bortezomib-based chemotherapy, and their renal function was monitored by plasma creatinine. Results: The number of HCO sessions ranged from 4 to 34 (mean 13). Six patients recovered kidney function, 3 regained partial function while 1 patient continued chronic dialysis. Patients with the largest reductions in LC during HCO treatments had the lowest creatinine at 6 and 9 months of follow-up. For comparison, only 2 out of 10 patients in a historic control group recovered kidney function. Conclusion: HCO dialysis combined with bortezomib results in good renal recovery with kidney function being dependent on the degree of LC lowering.

Randomized prospective study of high cut-off dialyzer membranes to reduce inflammation in chronic hemodialysis patients: THE PERCI-I TRIAL

Randomized prospective study of high cut-off dialyzer membranes to reduce inflammation in chronic hemodialysis patients: THE PERCI-I TRIAL

Clearance of Drugs for Multiple Myeloma Therapy During In Vitro High‐Cutoff Hemodialysis

Current chemotherapy for multiple myeloma is based on bortezomib (BOR), dexamethasone (DEX), and thalidomide (THA). The purpose of the present study was to examine their clearance during high-cutoff (HCO) hemodialysis and to accordingly apply the results to the dialytic removal of protein-bound substances in general. During in vitro hemodialysis with human blood (blood, dialysate, and ultrafiltration flow rates 250, 500 and 5 mL/min, respectively) comparing a highly permeable HCO dialyzer (Theralite, 2.1 m(2) ) to a high-flux dialyzer (PFX; 2.1 m(2) ), ultrafiltered volume was replaced by saline containing 30 g/L urea. After recirculation for equilibration, BOR was injected, and arterial and venous samples were drawn after 10, 11, and 12 min to measure the plasma clearance (K) of both urea and BOR. The same procedure was performed with THA and DEX. By mathematical simulation, the influence of varying plasma albumin concentrations (CHSA ) on the protein-bound drug fraction (PBF) and K was assessed. Plasma K values of HCO and PFX for THA, BOR, and DEX were about 40% (80 ± 7 vs. 65 ± 6 mL/min; P < 0.05), 70% (40 ± 8 vs. 33 ± 4 mL/min; P < 0.05), and 65% (47 ± 11 vs. 38 ± 7 mL/min; P < 0.05), respectively-lower (P < 0.0001) compared with urea (125 ± 7 vs. 122 ± 5 mL/min). K was highest (P < 0.0001) for THA. K was negatively correlated with CHSA (THA, r(2) = 0.58, P < 0.001; BOR, r(2) = 0.24, P < 0.05; DEX, r(2) = 0.22, P < 0.05). CHSA continually decreased (P < 0.05) over time only with HCO, resulting in lower calculated PBF. Compared with BOR and DEX (minimum 72 and 56%, respectively), the PBF of THA (37%) was significantly lower (P < 0.001). A mathematical simulation based on the K values of urea and the drugs reliably estimated PBF (r(2) = 0.886, P < 0.001). Drugs for multiple myeloma therapy are significantly removed with both HCO and PFX, with important implications for the dosing and timing of administration, particularly in patients with cast nephropathy receiving extended dialysis. If the Kurea of a dialyzer and the PBF of any given drug are known, Kdrug can be reliably estimated by mathematical simulation.

Elimination of Middle-Sized Uremic Solutes with High-Flux and High-Cut-Off Membranes: A Randomized in vivo Study

The elimination of substances between 10 and 50 kDa by conventional high-flux membranes is not satisfactory. We investigated in vivo the elimination of middle-sized uremic solutes by conventional polyflux (PF) and modified high-cut-off (HCO) membranes. All 12 patients underwent four treatments, two with the HCO dialyzer and two with the PF dialyzer, each in either a haemodialysis (HD) or haemodiafiltration (HDF) mode. The reduction ratio of urea, creatinine, β₂-microglobulin (β₂M), leptin, soluble TNF-RI, complement factor D, IL-6, sIL-6 receptor, advanced glycation end-products (AGEs) and albumin was determined. In addition, the amount removed was determined in the dialysate for β₂M, complement factor D, AGEs and albumin. Treatment with HCO removed β₂M, sTNF-RI, factor D, and high molecular AGE significantly better than conventional high-flux membranes. The albumin loss was higher when using HCO membranes. HCO membranes are a promising approach to improve removal of uremic toxins not affected by conventional high-flux membranes.

High-Cut Off Dialysis In Multiple Myeloma Patients With Dialysis Dependent Acute Renal Failure Shows Durable Renal Recovery: A Long-Term Follow Up Analysis

Acute kidney injury (AKI) either in primary diagnosis or at relapse is one of the frequent complications in multiple myeloma (MM). Myeloma cast nephropathy is induced by mechanical occlusion of the distal tubule by casts consisting of free light chains (FLC) and Tamm Horsfall protein. Impairment of renal function affects prognosis, with particularly poor outcomes in patients requiring hemodialysis with a historically reported median survival of 3-4 months. Introduction of novel therapeutic agents in MM therapy has improved MM response as well as renal outcome mainly due to a short time to initial response and consecutively reduction of the toxic FLC component. Extracorporeal light chain elimination in addition to chemotherapeutic treatment has been discussed controversially so far. We and others introduced the high-cut off (HCO) dialysis which allows effective elimination of FLC in an extended standard dialysis protocol. Recently, we demonstrated the efficacy of combined systemic and extracorporeal therapy regarding time to FLC reduction and renal recovery in a first case series of MM patients with dialysis-dependent AKI (Heyne et al., Ann Haematol 2012). Here, we report long-term renal outcome and overall survival data.19 MM patients with dialysis dependent AKI were treated between November 2006 and October 2009 with HCO dialysis in parallel to systemic chemotherapy. The applied chemotherapy was chosen by the treating haematologist. All data was calculated by intent-to-treat (ITT) analysis. Progression-free survival (PFS) was analysed from the first day of HCO dialysis to progression or death, whichever occurred first. Overall survival was calculated from the first day of HCO dialysis to death. For statistical analysis GraphPad Prism (GraphPad Software Inc., La Jolla/CA, USA) and R (R Foundation for Statistical Computing, Vienna) biostatistical software was used.The ITT cohort consisted of 19 patients. Median age was 69 (range 50-83) years. 10 patients had newly diagnosed, 9 relapsed or refractory MM. All patients had ISS stage III disease. Median serum FLC concentration at baseline was 8,580 (1 590-66 100) mg/L. Median serum creatinine was 6.8 (4.4-11.6) mg/dL, median eGFR 7.0 (3.3-10.9) mL/min/1.73m². Four (21%) early deaths occurred in the first three months of treatment, 2 patients with newly diagnosed and 2 patients with relapsed disease. Chemotherapy consisted mainly of bortezomib based regimens. As we reported previously, sustained renal recovery was achieved in 73.7% or 14/19 patients with a median time to independence of hemodialysis of 15 (4-64) days. In the long-term follow up analysis with a median follow-up of 62 months, 11/14 dialysis independent patients remained free of dialysis during further disease course. 3 patients again requiring dialysis all showed terminally refractory disease. Median PFS of the IIT population was 7.8 months for primary diagnosed and 4.8 months for relapsed and refractory patients, median OS of the whole population was 9.5 (range 2.8-not reached) months for primary diagnosed patients and 4.8 (range 1.0-19.8) months for the relapsed and refractory group.Combination of systemic treatment and HCO dialysis in patients with myeloma cast nephropathy and dialysis dependent renal failure results in durable renal remissions in the majority of patients. Close monitoring of patients and early treatment intervention can prevent recurrent severe AKI in myeloma relapse. Survival data reflect the critically ill patient population with high tumor burden and high-risk of early death, but also show encouraging long-term myeloma and renal remissions. The benefit of the additional HCO dialysis in addition to conventional chemotherapy is currently investigated in a randomised multicenter trial (EuLITE study). Disclosures:Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.

High cut-off dialysis as a salvage therapy option in high-dose methotrexate chemotherapy?

Dear Editor,High-dose methotrexate (HD-MTX) is a standard chemother-apy for a variety of malignancies [1]. Despite intensive pre-cautions, 2–10 % of the patients experience MTX-relatednephrotoxicity due to intratubular crystal precipitation andinduction of acute tubular necrosis (ATN) [2]. Acute kidneyinjury (AKI) leads to delayed MTX clearance and sustainedelevated MTX plasma levels, requiring prompt institution ofintensifiedleucovorinrescuetoavoidfataltoxicity[3].MTX-eliminating procedures, such as carboxypeptidase-G

Recovery of kidney function following delayed use of theralite™ dialyzer in a patient with myeloma cast nephropathy

We report the case of a 60- year- old man who presented with newly diagnosed multiple myeloma complicated by biopsy-proven acute cast nephropathy, requiring hemodialysis, plasmapheresis and chemotherapy. After remaining dialysis dependent for 5 weeks, a high cut-off (HCO) dialyzer, intended to use for the removal of plasma substances with a molecular weight of up to 45 kDa such as free light chains, was introduced to his outpatient 4-hour hemodialysis regimen with an increase in treatment frequency to 4 sessions per week. Following 6 weeks of dialysis with the HCO dialyzer, serum levels of free κ light chains declined by more than 75%. Concurrently, he recovered kidney function and discontinued dialysis. He subsequently received a successful autologous stem-cell transplant. We discuss the potential merit of using the HCO dialyzer late in the course of the care of patients with myeloma cast nephropathy who are dialysis dependent.

New High-Cutoff Dialyzer Allows Improved Middle Molecule Clearance without an Increase in Albumin Loss: A Clinical Crossover Comparison in Extended Dialysis

Background: Accumulation of middle molecules is thought to have adverse effects in patients with acute kidney injury (AKI). Elimination of middle molecules by non-convective means, i.e. hemodialysis, remains difficult. The aim of the study was to investigate the removal characteristics of a new high permeability membrane in AKI patients undergoing extended dialysis (ED). Patients and Methods: We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8 m², FMC, Germany) and AV 1000S (1.8 m², FMC) in 11 critically ill patients with AKI. β₂-Microglobulin, cystatin c, creatinine, and urea were measured before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer clearances, and mass in the total collected dialysate were determined. Results: Dialyzer clearance of β₂-microglobulin (EMiC2: 52 ± 1.7 ml/min, AV 1000S: 41.7 ± 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 ± 1.2 ml/min, AV 1000S: 34.2 ± 2.3 ml/min, p < 0.0001) was markedly different, as was the reduction of serum levels of β₂-microglobulin (EMiC2: 54.3 ± 3.6%, AV 1000S: 39.1 ± 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 ± 2.6%, AV 1000S: 28.0 ± 3.9%, p = 0.043). Additionally, we observed a higher total amount of these substances in the collected dialysate. There was no significant difference in the total amount of albumin eliminated per treatment. Conclusion: The new EMiC2 dialyzer enhances removal of middle molecules without an increase in albumin loss. The clinical relevance of this finding needs to be determined.

Randomized Controlled Pilot Study of 2 Weeks' Treatment With High Cutoff Membrane for Hemodialysis Patients With Elevated C‐Reactive Protein

Chronic inflammation in hemodialysis (HD) patients is associated with cardiovascular complications and mortality. Circulating immune active proteins in the molecular range 15-45 kD that cannot be efficiently cleared by high-flux (HF) dialysis may be causally involved. We intended to test the feasibility of using a high cutoff (HCO) dialyzer in chronic HD patients and its influence on inflammation and monocyte activation. The Gambro HCO1100 dialyzer was compared to a conventional HF membrane in a randomized double-blind crossover trial in 19 chronic HD patients selected for the presence of elevated serum C-reactive protein levels. Patients were treated for six consecutive dialysis sessions (2 weeks) with each membrane. Safety analysis recorded adverse events and albumin losses through the protein-leaking membranes. Efficacy analysis observed reductions in the number of proinflammatory (CD14+CD16+) monocyte subpopulations in circulating blood. Treatment with the HCO membrane was well tolerated, although the number of adverse events was slightly higher. Despite significant serum albumin loss (from 34.1 ± 2.7 to 29.6 ± 3.0 g/L; P < 0.01), there was no need to supplement albumin, and rising activity of cholinesterase during HCO treatment indicated compensation by enhanced hepatic synthesis. The HCO membrane cleared high amounts of proinflammatory cytokines, but did not reduce predialysis inflammatory monocytes and markers. Although the time of HD session was extended, the study was hampered by a lower Kt/V in the HCO compared to the HF period. Treatment of chronic HD patients with this HCO dialyzer for 2 weeks is tolerable in terms of albumin loss and able to clear proinflammatory cytokines; however, this was not sufficient to decrease monocyte activation. Therefore, a more selective, less albumin-leaking membrane is desirable to allow prolonged high-efficient dialysis with more effective cytokine clearance.

High cut-off dialyser haemodialysis in cast nephropathy.

Sir, The importance of renal function in the prognosis of patients with multiple myeloma (MM) has been well established and rapid reversal of renal failure may offer the best long-term outcome. The use of extracorporeal means of removing immunoglobulin free light chains (FLCs) responsible for cast nephropathy in patients with MM is controversial. Nephrologists are interested in a treatment strategy combining chemotherapy and extracorporeal treatments in patients with biopsy-proven cast nephropathy or a high probability of cast nephropathy (defined as >200 mg/dL on the FLC assay). Some previous studies have shown that the plasma exchange is unable to remove sufficient FLCs for clinical benefits. The issue of whether an extended duration of dialysis with high cut-off (HCO) dialysers is more effective than plasma exchange at removing FLC or reversing renal failure is not settled [1]. Hutchison and Leung reported that a 60% reduction in FLCs by Day 21 is associated with recovery of renal function for 80% of the studied patients [2]. Our experience: a 43-year-old man, who was not complaining of any previous disease and with a previously normal renal function, suffering from biopsy proven lambda myeloma kidney, without any histological sign of chronic renal damage, and renal failure dialysis dependant, in 2 weeks received 10 haemodialysis (HD) treatments with HCO-dialyser (Theralite Gambro). We quantified the concentration of FLCs by nephelometry (Biocite, N latex test; Siemens). Initially, λ FLC concentration was 5500 mg/L. At the end of HCO dialyser HD cycle, the concentration was 94.80 mg/L (Table 1). Table 1. Concentrations and ratios of FLC before and after HCO-dialyser HDa We did not observe any adverse effects. We observed by Day 7 a sustained and >50% reduction of FLCs with dialysis alone before the chemotherapy was initiated. After the third HCO-dialyser HD, the patient started PAD Orlowsky chemotherapy (Bortezomib–Doxorubicin–Dexamethasone) with successful haematological result but with partial renal function recovery. Currently (5 months after HCO-dialyser treatment), the patient is on maintenance HD two times a week. Some reports show a recovery of renal function after several months. If the patient does not recover normal renal function, we think that a new kidney biopsy can help his management.

Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma.

Acute renal failure (ARF) occurs in 12%-20% of all multiple myeloma (MM) cases, and the survival of these patients depends on renal function recovery. Renal function is not recovered in 75% of dialysis-dependent patients, and their mean survival with replacement therapy is less than one year. Renal tubular disease is the most frequent cause of renal failure. It is present in more than 55% of renal failure cases and in 75% of those requiring dialysis. Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function. One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis, but its efficacy has not yet been clearly proven. Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers (HCO-HD), obtaining a recovery rate of more than 60%. We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis. Then, we review the pros and cons of this technique. Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500 mg/l were treated with 8-hour haemodialysis sessions with an HCO-HD filter. Before and after each session, serum free light chain levels were measured by nephelometry; other parameters were recorded as well. At the same time, patients underwent chemotherapy according to protocols. The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable, from 7 days to more than 1 year. We performed 90 extended sessions with HCO-HD filters, and each patient underwent between 6 and 40 sessions. Free light chain levels decreased by a mean of 65% between treatment onset and completion, except in one patient who experienced a 12.6% reduction. The mean percentage of reduction of light chain levels per session was 54.98% ± 17.27%. A complication occurred during 28% of the sessions. Of these complications, 48% were due to system coagulation. There were no major changes in pre-dialysis albumin, calcium, phosphorous or magnesium levels, although lower values that were not clinically relevant were recorded in one case. Renal function was recovered in 3 patients, they are alive and dialysis-free. In biopsied cases that recovered renal function, the specimen showed tubular nephropathy only. Those patients who took longer to be diagnosed did not recover their renal function, and when biopsied, they were diagnosed with renal tubular disease and light chain deposition disease. We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease, and achieved a recovery rate of 50% in our cases. Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis, histological findings, promptness of starting chemotherapy, response to chemotherapy, and effectiveness of light chain extraction. In any case, further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques.

An International Study of High Cut-off Hemodialysis for the Management of Myeloma Kidney,

Abstract 3974▪▪This icon denotes a clinically relevant abstract Background:An early reduction in serum free light chains (FLC) improves outcomes for patients with myeloma kidney. The purpose of this study was to assess how high cut-off (HCO) dialysers are being used internationally to achieve this target. Methods:Data was collected for 54 patients, from 18 centers in 10 countries. Clinical presentation and treatment parameters, including details of removal of FLCs with high cut off hemodialysis and chemotherapy treatment, were captured using a web-based collection database. Demographics:All patients were Caucasian, median age of 65 years (range 43–81). Median biochemistry at presentation was: GFR of 8mls/min/1.73m2 (1–27). creatinine 633.5μmol (168–2263); calcium 2.3mmol/L (0.91–3.83); albumin 34g/L (14–46) and β2M 9.45mg/L (0–55.7). Baseline monoclonal κ and λ FLCs levels were: 5070mg/L (range 2250–20200) and 4200mg/L (range 300–13300), respectively. Of the patients who received a renal biopsy, 81% had myeloma kidney as their primary diagnosis. For initial chemotherapy prescriptions: 78% received bortezomib and 34% received thalidomide. 68.75% of the patients were treated with the Theralite HCO dialyzer; the other 31.25% received treatment with the HCO1100 dialyzer. There was a total of 626 HCO dialysis sessions recorded, with each patient receiving on average 13 session each (median, range 3–35) treatments per patient. Of the 54 patients, only 3 were treated with HDF. Results:73.2% of patients demonstrated a decreased serum FLC level over the course of treatment, with 86.7% of these patients demonstrated decreased levels by day 12. The median FLC reduction achieved was 72.96% (15.09–99.62%) by day 12 and 93.03% (40.23–99.96%) by the last dialysis treatment. There was no difference in the percentage FLC reduction achieved between bortezomib (median: total 94.09%, day 12 79.14%) and thalidomide (median: total 77.65%, day 12 66.51%) treatment groups (total p=0.179, day 12 p=0.300). FLC removal was significantly increased in patients receiving Theralite treatment over those receiving HCO1100 at both day 12 (p=0.030) and by the end of treatment (p=0.031) Dialysis independence occurred in 68.2% of patients, median time 32 days (10–249). Patients who became independent of dialysis had significantly greater reductions in serum FLC by day 12 (p=0.032). No significant adverse events related to the study device were reported. Conclusion:Reducing FLC in patients with myeloma kidney is associated with increased levels of dialysis independence. This study adds further evidence that a combination of chemotherapy and FLC removal by HCO hemodialysis improves patient outcomes following acute kidney injury secondary to multiple myeloma. Disclosures:Hutchison:The Binding Site: Honoraria. Bevins:The Binding Site Group Ltd: Employment. Mead:The Binding Site Group Ltd: Employment.

Reversible acute kidney injury (AKI) by active removal of serum light chains in an HIV positive patient with myeloma kidney

The association of HIV and myeloma has rarely been reported in the literature. This following case discusses the presentation of acute kidney injury (AKI) in a 53-year-old lady with HIV, subsequently diagnosed with myeloma. Furthermore, we describe recovery of renal function and dialysis independence using a combination of light chain removal by dialysis with a high cut-off dialyzer and chemotherapy. Physical examination, urine, blood tests, renal biopsy, bone marrow aspirate and trephine, US scan. Myeloma. Dialysis and chemotherapy.

Actualités dans le traitement du myélome avec insuffisance rénale

Renal failure, mostly related to myeloma cast nephropathy (MCN), is a frequent complication of multiple myeloma (MM), which occurs in up to 50% of patients during the course of the disease. Persistent renal failure in MM is associated with poor survival. Treatment of MCN relies on urgent symptomatic measures (alkalinisation, rehydration, correction of hypercalcemia, and withdrawal of nephrotoxic drugs), with rapid introduction of chemotherapy to efficiently reduce the production of monoclonal light chains (LC). Recent studies suggest that, in patients with MM and severe renal failure due to MCN, rapid removal of circulating LC, through intensive hemodialysis sessions using a new generation high cut-off dialysis membrane, might result in dialysis withdrawal in most patients. If the development of intensive therapy and new efficient chemotherapy agents (thalidomide, bortezomib, lenalidomide) has transformed the care and prognosis of MM, the modalities and safety of these therapeutic regimens in patients with renal failure remain to be defined. The association of bortezomib with dexamethasone should be considered currently as first-line treatment in patients with MM and impaired renal function.

Modelled cost-effectiveness of high cut-off haemodialysis compared to standard haemodialysis in the management of myeloma kidney

Background:Approximately 10–20% of multiple myeloma patients experience dialysis-dependent renal failure. This is principally due to myeloma kidney, a tubulointerstitial injury caused by high circulating concentrations of monoclonal free light chains. Studies have found that between 3% and 37% of patients with myeloma kidney requiring dialysis recover renal function. In-vivo studies indicate that extended haemodialysis using high cut-off dialysers (HCO-HD) can remove significant quantities of free light chains and is associated with a renal recovery rate of 63–74% in these patients.Objective:The objective of this study was to assess the cost-effectiveness of HCO-HD compared to standard HD in the management of myeloma kidney.Methods:The study used a lifetime Excel-based decision tree model that followed all patients from treatment of the initial presentation with myeloma kidney requiring dialysis to death. It was populated with published clinical data, United Kingdom costs and expert opinion, using a National Health Service perspective and 3.5% annual discounting.Results:HCO-HD was dominant to standard HD, meaning it was both more effective (greater life years and quality adjusted life years) and less costly, due to a greater increase in the proportion of patients recovering renal function. The model projected lifetime costs of £31,345 per patient for patients treated with standard haemodialysis only and £24,845 for the new treatment (discounted). The model predicted an average survival of 19.92 months for patients on standard HD and 33.90 months for the new therapy (discounted).Conclusions:The analysis found that treatment of myeloma kidney using an extended schedule of HCO-HD may substantially improve renal recovery in multiple myeloma patients compared to standard HD, resulting in greater life expectancy and cost savings due to avoided chronic dialysis. Limitations of the study include those common to rare diseases including small study sizes and limited natural history data.