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

Abstract

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.We describe seven newly diagnosed myeloma patients with acute renal failure due to cast nephropathy successfully treated by HCOD and bortezomibbased therapy. Detailed patient information is provided in Table I. All patients had very high sFLC concentrations (median 13,300 mg/L, range 4,130-20,200 mg/L) on admission and all but one, in whom biopsy was not carried out, biopsy-proven MCN. We carried out daily hemodialysis sessions for 6 hr whenever possible using the HCOD (Theralite 1 , Gambro). However, for the first dialysis session we used a low-flux dialyzer for only 3 hr to prevent dysequilibrium problems in those patients who were uremic. A centrally placed dialysis cannula was utilized. For anticoagulation, a low-molecular weight heparin product was used. We paid special attention to electrolyte balance by measuring potassium, sodium, calcium, phosphate, and blood pH every hour during HCOD. Fluid balance was maintained at euvolemia by either ultrafiltration or rehydration. A rapid nonsustained decline in sFLC concentration after each HCOD was observed. HCOD was continued until the sFLC concentration steadied to below 500 mg/L. Bortezomib-based therapy was instituted as early as possible, usually by the third session. No serious dialysis related complication occurred. All but one patient became dialysis independent. One patient died after the completed treatment schedule in a nondialysis-dependent state due to myocardial infarction. Autologous stem cell transplantation was later performed for three patients and complete remission was achieved.Effective chemotherapy is generally recognized as the main element in myeloma treatment, but its effect on sFLC is seen only in a matter of several days or weeks. A novel anti-myeloma agent, bortezomib, has more rapid disease control compared with old chemotherapy regimens, but even its effects are not seen within days, during which period the kidneys may suffer irreversible damage. Evidence regarding the benefit of plasma exchange to remove sFLC has been conflicting [1], but Burnette et al. [2] recently reported renal improvement in MCN when combining plasma exchange with bortezomib-based therapy in a case series with 14 patients. HCOD has still better potential to eliminate sFLC than plasma exchange [3]. Case reports and a small open-label study concerning chemotherapy combined with HCODs have been published and a randomized controlled trial is ongoing [4,5]. Our recent experience combining HCOD wit...

Bortezomib‐based therapy combined with high cut‐off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment

“…However, 75% of these patients were newly diagnosed and only 58% received bortezomib as part of therapy. More recently, the combination of HCOD with bortezomib-based therapy was evaluated in a limited series of 7 patients with newly diagnosed MM and acute RI [32]. All but one of them became dialysis independent after therapy, suggesting that HCOD is highly effective in the management of MM and RI.…”

Current Trends of Renal Impairment in Multiple Myeloma

“…There are several other small studies which have highlighted the benefit of HCO haemodialysis in renal function recovery in patients with MM and severe RI (table 3) [122,123,124,125,126,127]; however, supplementation of HCO haemodialysis to current standard of care in assisting renal outcome and in doing so long-term patient outcome needs to be carefully investigated, and hence results of the EUropean trial of free LIght chain removal by exTEnded haemodialysis in cast nephropathy (EuLITE) and studies in patients with MM and renal failure due to MCN (MYRE) are awaited [128,129]. …”

Bortezomib improves outcome after SCT in multiple myeloma patients with end-stage renal failure

“…18,19 Several haemodialysis techniques have recently become available for patients with dialysis-dependent acute renal failure secondary to myeloma kidney; extended high cut-off haemodialysis in combination with standard chemotherapy seems to improve renal function. 20 Besides chemotherapy, extracorporeal elimination procedures such as plasma exchange have been applied as adjuvant strategies to eliminate free light chains from circulating blood.…”