High Cut-off Hemodialysis Research Articles

Some Kinetic Considerations in High Cut‐Off Hemodiafiltration for Acute Myoglobinuric Renal Failure

The kinetics of myoglobin in severe rhabdomyolysis and dialysis-dependent myoglobinuric acute kidney injury (Mb-AKI) is still not well elucidated, and more detailed knowledge could improve the now empiric use of rapid extracorporeal myoglobin removal by high cut-off (HCO) hemodialysis treatments. Eighteen adult patients with severe dialysis-dependent Mb-AKI (median serum concentration of myoglobin 57.4 mg/L) participated in the prospective clinical study, assessing myoglobin kinetics during HCO hemodiafiltration (HCO HDF). High initial serum concentrations of myoglobin (median 57.4 mg/L), together with protracted myoglobin appearance in the blood, indicated a large accumulation of myoglobin in body fluids. Extra-renal endogenous metabolic myoglobin clearance was delayed, with a slow exponential fall in serum myoglobin (t½ 35 h). A mean myoglobin clearance of 90-94 mL/min, a reduction ratio of 80%, and a rapid exponential fall (t½ 1 h) in serum and dialysate myoglobin were achieved by HCO HDF. Half of the cumulative myoglobin removal was accomplished in 3-5 h, with an additional removal of 7% each hour thereafter. A 2.4-fold rebound in serum myoglobin followed the HCO procedures. Large amounts of myoglobin are released into the circulation, and its endogenous metabolic clearance in dialysis-dependent Mb-AKI is slow. Owing to its rapid and highly efficient myoglobin elimination, HCO HDF may represent a valuable tool in the initial management of severe Mb-AKI, with a potential for earlier application in the future.

EARLY APPLICATION OF HIGH CUT-OFF HAEMODYALISIS FOR DE-NOVO MYELOMA NEPHROPATHY IS ASSOCIATED WITH LONG-TERM DIALYSIS-INDEPENDENCY AND RENAL RECOVERY

BackgroundMultiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that early reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used.Patients and MethodsIn this study, four cases with MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established.ResultsAfter a medial follow up of 26 months, (range, 13–36) our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early in the treatment and became dialysis-independent. One patient with relapsed myeloma remained dialysis-dependent.ConclusionIn summary, our study suggests that in myeloma nephropathy associated with light-chain MM, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further randomized trials to confirm our results are warranted.

Multiple myeloma and kidney disease.

Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.

Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience.

Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.

Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: A case report

To report endotoxemia presented in a case with multiple myeloma (MM) treated by high cutoff hemodialysis (HCO-HD) being prevented by using ultrapure dialysate. A female inpatient with MM received six times HCO-HD (HCO 2100 dialyzer) within 3 weeks after initiation of a chemotherapy based on vincristine+epirubicin+dexamethasone protocol. Conventional dialysate was used in the first three times and then changed to ultrapure dialysate due to elevation of body temperature after HCO-HD. Free light chains (FLC) and endotoxin levels in blood and dialysate were monitored. After six times HCO-HD, her serum FLC λ decreased from 4689 mg/L to 492.7 mg/L, with a trend of decline of serum creatinine. The clearance, reduction ratio, and removal amount of FLC λ was 38.4 mL/min, 71.0-85.2%, and 9.06-18.02 g, respectively, in the setting of dialysate flow rate 500 mL/min, while in the setting of dialysate flow rate 200 mL/min, the removal efficacy of FLC λ was lower than the former. A rise of body temperature up to 38.5°C after treatment and endotoxemia (endotoxin levels 0.122 EU/mL) was found when using conventional dialysate (endotoxin levels 0.112-0.145 EU/mL), but not seen after changing to ultrapure dialysate. Combined with appropriate chemotherapy, HCO-HD can effectively remove and reduce blood FLC. Attention should be paid to the endotoxemia and the rise of temperature after treatment when conventional dialysate is used, which can be prevented by using ultrapure dialysate.

Myeloma kidney: advances in molecular mechanisms of acute kidney injury open novel therapeutic opportunities

Renal impairment is a common complication of multiple myeloma (MM) and is supported in virtually all patients by a tubulointerstitial pathology that results from high serum concentrations of monoclonal free light chains (FLCs). The proteins involved in the kidney injury and the analysis of their binding interactions have been thoroughly investigated and the main pathogenic mechanisms are being elucidated. Early sustained reduction of circulating FLC leads to improved renal recovery rates that translate into improved quality of life and survival. The mainstay of therapy is presently the removal of aggravating factors (dehydration, hypercalcaemia, nephrotoxic drugs) and the prompt institution of rapidly acting novel chemotherapy combinations. This approach allows the rescue of kidney function in more than two-thirds of patients. High cut-off haemodialysis dialysers may potentially add clinical benefits and the outcomes of controlled trials are eagerly awaited. Basic research findings have led to the design of targeted drugs that prevented the functional manifestations of acute kidney injury in animal models. There is now hope to prevent the renal damage in patients with MM.

Extended High Cutoff On‐Line Hemodiafiltration Is Superior to Extended High Cutoff Hemodialysis in Removal of Free Light Chain Immunoglobulin of Myeloma Cast Nephropathy

Extended High Cutoff On‐Line Hemodiafiltration Is Superior to Extended High Cutoff Hemodialysis in Removal of Free Light Chain Immunoglobulin of Myeloma Cast Nephropathy

High cut‐off hemodialysis and bortezomib‐based therapy to rescue kidneys in myeloma‐dependent cast nephropathy

Myeloma-dependent cast nephropathy (MCN) is a medical emergency where prompt medical intervention is essential to rescue the kidneys from irreversible damage and the patient from lifelong dialysis. Evidence of the benefit of plasma exchange in removing serum free light chains (sFLC) has been controversial [1,2]. According to our recent experience, high cut-off hemodialysis (HCOD) with specially designed dialyzers reduces the level of sFLC concentration within hours and improves renal function in MCN in the long term when combined with effective bortezomib-based chemotherapy.

Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis

To determine the efficacy of immunoglobulin free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) as an adjuvant treatment to chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM). Sixty-seven patients with dialysis-dependent renal failure secondary to MM were treated with HCO-HD and chemotherapy. The population was predominantly male (62.7%) with new presentation MM (75%) and did not have a history of chronic kidney disease (84%). The mean serum creatinine at presentation was 662 (SD = 349) μmol/L and of the 56.7% of patients who had a renal biopsy, 86.7% had cast nephropathy as the principal diagnosis. Eighty-five percent of patients were treated with a chemotherapy regime consisting of dexamethasone in combination with a novel agent (bortezomib or thalidomide). The median number of HCO-HD sessions was 11 (range 3-45), 97% received an extended dialysis regime. Seventy-six percent of the population had a sustained reduction in serum FLC concentrations by Day 12, of these 71% subsequently became independent of dialysis. In total, 63% of population became independent of dialysis. Factors which predicted independence of dialysis were the degree of FLC reduction at Days 12 (P = 0.002) and 21 (P = 0.005) and the time to initiating HCO-HD (P = 0.006). The combination of extended HCO-HD and chemotherapy resulted in sustained reductions in serum FLC concentrations in the majority of patients and a high rate of independence of dialysis.

Extracorporeal light chain elimination: high cut-off (HCO) hemodialysis parallel to chemotherapy allows for a high proportion of renal recovery in multiple myeloma patients with dialysis-dependent acute kidney injury

Acute kidney injury (AKI) is frequent in multiple myeloma (MM) patients and strongly affects prognosis, with particularly poor outcomes in patients requiring hemodialysis. Introduction of the novel therapeutic agents to MM therapy has improved myeloma response and renal outcome. This case series reviews the efficacy of combined systemic and extracorporeal therapy to further optimize time to light chain (serum-free light chain (sFLC)) reduction and renal recovery in MM patients with dialysis-dependent AKI (n = 19). High cut-off (HCO) hemodialysis for extracorporeal sFLC removal was initiated in parallel to chemotherapy. Combined therapy resulted in early sFLC response after a median of 13 (range 4-48) days and 6 (3-22) HCO hemodialysis sessions. Time to sFLC response was shorter in patients recovering renal function. Median time to dialysis independence was 15 (4-64) days. By intent-to-treat analysis, sustained renal recovery was achieved in 73.7% (77.8% adjusted for death) of patients. In multivariate analysis, duration of AKI prior to initiation of therapy was an independent predictor of renal functional outcome. Combining HCO hemodialysis for extracorporeal sFLC elimination and effective chemotherapy is a novel treatment strategy allowing for early and sustained sFLC reduction and a high proportion of renal recovery in these patients. Timely diagnosis and onset of therapy is essential for improving renal outcome.

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.

Renal Improvement in Myeloma with Plasma Exchange

To the Editor: Burnette et al. (June 16 issue)1 evaluated bortezomib-based chemotherapy and plasma exchange for the management of myeloma kidney. The reported renal recovery rate of 86% will probably lead to improved patient survival. However, interpretation of these results should be approached with caution. The authors’ principal finding confirmed that of a previous study showing that an early reduction in concentrations of serum free light chains is associated with renal recovery.2 The authors did not show the relative contribution of plasma exchange to the achievement of this reduction. Previous studies have shown the inability of plasma exchange to provide a meaningful magnitude of free light-chain removal, as compared with extended high-cutoff hemodialysis.3 In addition, the only large controlled trial of plasma exchange involving these patients did not show a clinical benefit.4 Therefore, the early reduction of levels of free light chains probably represents the efficacy of the chemotherapy rather than the plasma exchange. Controlled studies assessing the additional benefit of plasma exchange beyond effective chemotherapy, similar to the ongoing trials EULITE (European Trial of Free Light Chain Removal by Extended Haemodialysis in Cast Nephropathy; Current Controlled Trials number, ISRCTN45967602) and MYRE (Studies in Patients with Multiple Myeloma and Renal Failure Due to Myeloma Cast Nephropathy; ClinicalTrials.gov number, NCT01208818) assessing extended hemodialysis, are warranted before any clinical recommendations can be made.

Impact of free light chain hemodialysis in myeloma cast nephropathy: A case–control study

New very high permeability dialysis membranes have been developed to enable the clearance of free light chains in myeloma cast nephropathy. These new dialysis techniques, in combination with chemotherapy, should allow improved prognosis in patients with myeloma cast nephropathy. We report a prospective observational study comparing patients who underwent hemodialysis in our center in 2009 for cast nephropathy revealing multiple myeloma vs. patients treated for the same condition during the same period in other centers in our region. The main difference in the management protocols was the use of high cutoff (HCO) membranes in our center. We described the clinical features, the management protocols, and the outcomes as of June 1, 2010. In 2009, five patients were treated for myeloma cast nephropathy with HCO hemodialysis in our center. At 386 ± 100 days follow-up, one patient died, while three of the five patients recovered their renal function, allowing cessation of hemodialysis. During the same period, five patients were treated for myeloma cast nephropathy in other centers in our region. At 398 ± 131 days follow-up, four patients died, and none of the patients recovered renal function, allowing cessation of hemodialysis. In our study, light chain clearance allowed recovery of renal function and cessation of hemodialysis in three of five patients with acute kidney injury secondary to myeloma cast nephropathy. A randomized trial comparing this technique with conventional hemodialysis techniques should be conducted to raise the level of proof for this therapeutic option. The overall prognosis, including quality of life and cost-effectiveness, of HCO hemodialysis should also be examined.

High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

A 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has now been continued for >3½ years. We were also able to induce remission of iFSGS in this patient by treatment with high cut-off haemodialysis using the Theralite™ dialyser. This observation lends support for the pathophysiological role of an as yet unknown, circulating glomerular filtration barrier permeability factor with an estimated weight of between 30 and 50 kDa.

Aggregated serum free light chains may prevent adequate removal by high cut-off haemodialysis

Free light chain (FLC) removal by high cut-off haemodialysis has been described as an adjuvant therapy for the management of patients with severe renal failure complicating multiple myeloma. The two cases reported here are the first patients in whom this treatment did not remove FLCs. In both patient's sera, size-exclusion chromatography identified large FLC aggregates, with molecular weights above the cut-off of the dialyser. It is important for clinicians to be aware of FLC aggregates as a reason for failure to remove FLCs by this new modality.

Extracorporeal Treatment of Cast Nephropathy

Acute kidney injury (AKI) is common in patients with multiple myeloma (MM), most commonly caused by cast nephropathy resulting from precipitation of free light chains (FLC) in renal tubules. AKI may be irreversible and require dialysis and predicts a poor prognosis. Reduction in serum FLC concentration is thought to be associated with improved likelihood of kidney function recovery in MM patients with AKI. Plasma exchange (PE), by removing circulating FLC, has been used as a treatment modality to improve kidney function in MM, although its efficacy remains uncertain. Extracorporeal treatment with extended high cutoff hemodialysis (HCO-HD) has also recently been studied as a potentially more effective means of FLC removal. Both PE and HCO-HD may be beneficial in some patients, but only when used as adjuncts to successful chemotherapy. Further research is necessary to establish the specific efficacy of each of these extracorporeal methods in the treatment of cast nephropathy.

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.

A Review of Multiple Myeloma Patients on Dialysis Treated with High Cutoff Hemodialysis

AbstractAbstract 5002 Background:Kidney failure is a major cause of morbidity in patients with Multiple Myeloma (MM). While up to half of MM patients can be shown to have renal impairment, 10% will become dialysis dependent. The main mechanism of kidney failure is cast nephropathy, which is linked to high amounts of circulating free light chains. A proposed strategy to prevent this outcome is the use of extended high cutoff (HCO) dialysis. An ongoing randomized controlled trial is testing the Gambro HCO1100 filter. Here we report the use of another dialyzer (Bellco Phylther), which has a smaller pore size than the Gambro filter, but which may prove to be as effective and is less costly. Methods:We present three patients with symptomatic MM, elevated κ or λ serum free light chains (>500mg/L), biopsy confirmed cast nephropathy, and kidney failure (estimated GFR <15ml/min/1.73 m2) requiring dialysis. In all patients, dialysis consisted of 10 hemodiafiltration dialysis sessions in the first two weeks and three times a week thereafter using a high flux Bellco Phylther HF22SD dialyzer (Bellco, Modena, Italy). All patients received concurrent chemotherapy: bortezomib 1.3mg/m2 IV and dexamethasone 40mg po on days 1, 4, 8 and 11 of a 21 day cycle and liposomal doxorubicin at 30mg/m2 on day 4 of every cycle. Serum free light chains were determined pre- and immediately post-dialysis using a nephelometric immunoassay (FREELITE, The Binding Site, Birmingham UK). Results:We observed significant (>50%) and rapid reductions in sFLCs. These reductions were sustained at 3 months in all cases, likely because of effective anti-myeloma treatment. Two of the three patients had recovery of kidney function and remain dialysis-independent at least 6 months after cessation of dialysis. Interestingly, the only patient that did not recover kidney function was also found to have tubulointerstitial disease on renal biopsy in addition to cast nephropathy. Conclusions:The HCO Bellco Phylther dialyzer appears effective in the rapid reduction of sFLCs in light chain MM patients with cast nephropathy requiring dialysis and concurrent anti-myeloma drug therapy. While the numbers are small, our review suggests that patients with uncomplicated MM cast nephropathy may benefit from aggressive hemodiafiltration with this HCO membrane. This dialysis membrane and protocol are worth considering for further study in patients with MM cast nephropathy. Disclosures:No relevant conflicts of interest to declare.

Management options for cast nephropathy in multiple myeloma

This article reviews the relevance of the following areas to the contemporary management of cast nephropathy in multiple myeloma: immunoassays that quantify immunoglobulin free light chain (FLC), novel chemotherapy agents and high cut-off (protein-permeable) haemodialysis, which are under evaluation in patients with cast nephropathy and multiple myeloma. Clonal serum FLC can be measured with high sensitivity and specificity and used to rapidly screen for cast nephropathy. A sustained decrease in serum FLC levels within 3 weeks of starting treatment is associated with renal recovery; novel chemotherapy agents can maximize this early response. Although plasma exchange does not produce clinical benefit, pilot studies of high cut-off haemodialysis show high efficacy for serum FLC removal. If a patient with cast nephropathy and severe acute kidney injury remains dialysis-dependent, the prognosis is poor. A prompt diagnosis and commencement of effective chemotherapy is a critical determinant of renal recovery. A randomized controlled trial of high cut-off haemodialysis in patients with cast nephropathy, who all receive bortezomib-based chemotherapy, is underway.

Improving Outcomes in Patients with Renal Failure Secondary to Multiple Myeloma: Results From ChAR2M2.

Abstract 1875Poster Board I-900 Study purpose:To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods:A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results:Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion:Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures:No relevant conflicts of interest to declare.