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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
LETTER TO THE EDITOR  
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1445-1447
Favorable kidney recovery by extracorporeal light chain removal and anti-myeloma treatments in patients with newly diagnosed multiple myeloma and acute renal failure


1 Nephrology Unit, Saint Eugenio Hospital, Rome, Italy
2 Hematology Unit and Laboratory Medicine Unit, Saint Eugenio Hospital, Rome, Italy

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Date of Web Publication29-Jan-2021
 

How to cite this article:
Silvestrini G, Tatangelo P, Scaramucci L, Sfara G, Bondanini F, Niscola P, de Fabritiis P, Palumbo R. Favorable kidney recovery by extracorporeal light chain removal and anti-myeloma treatments in patients with newly diagnosed multiple myeloma and acute renal failure. Saudi J Kidney Dis Transpl 2020;31:1445-7

How to cite this URL:
Silvestrini G, Tatangelo P, Scaramucci L, Sfara G, Bondanini F, Niscola P, de Fabritiis P, Palumbo R. Favorable kidney recovery by extracorporeal light chain removal and anti-myeloma treatments in patients with newly diagnosed multiple myeloma and acute renal failure. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Mar 2];31:1445-7. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1445/308370


To the Editor,

Renal involvement is the principal cause of morbidity for patients with multiple myeloma (MM). Acute kidney injury (AKI) is a frequent accompaniment of MM, which results in significant short-term and long-term morbidity as well as mortality which requires complex clinical management.[1],[2] In MM, severe AKI (requiring dialysis) is predominantly due to paraprotein-mediated nephrotoxicity, typically secondary to cast nephropathy (CN) induced by intratubular obstruction from precipitation of monoclonal serum-free light chains (sFLC) as well as direct tubular toxicities exerted by these endogenous proteins via stimulation of nuclear factor (NF)-KB inflammatory pathways.[1] AKI complicating MM represents a medical urgency requiring a prompt and immediate intervention in order to avoid the rapid progression of the renal insults to ire-versible kidney damages. Current mainstays of CN treatment are early removal of the precipitating factors, such as nephrotoxic drugs, acidosis, and dehydration, together with rapid reduction of sFLC levels.[1],[2],[3],[4] In addition, the proteasome inhibitor bortezomib has been found to significantly improve the response rates in MM due to its ability to rapidly reduce sFLC levels and now represents the backbone of bortezomib-based regimens highly effective to allow dialysis independence and rapid renal recovery in MM patients complicated by AKI.[56]

As an adjunct to anti-myeloma treatment, several new extracorporeal techniques have emerged as further means to reduce sFLC concentrations in the treatment of CN.[7],[8] Despite these awareness and advances in our understanding of the pathogenesis of these hemato-nephrological pathological processes as well as the need for prompt and medically complex and dedicated approaches, there is a general lack of guidelines about standardized treatment approaches to achieve improved patient outcomes.[3],[6],[9] Although a close collaboration between hematologists and nephro-logists with integrated clinical interventional plans is desirable, often, only a mere consulting role is provided. Our group now have such an integrated plan and the experiences are ongoing.[9] In the past, some attempts to remove sFLC by extracorporeal techniques were made without relevant advantage using plasma exchange and coupled plasma filtration adsorption.[10] Then, the focus was on the use of hemodialysis (HD) membranes with high cutoff (HCO) with encouraging results in some cases but never definitive.[4],[7],[8],[10] The data of two European multi-centric randomized controlled trials, with different design, undertaken to verify the effectiveness of intervention regimens based on the use of HCO membranes in a larger population, have recently been published.[7],[8] The results of the two studies are different and are difficult to compare for the different design characteristics; the EuLITE[7] study did not show significant differences in the two groups, while the MYRE study showed a better renal recovery in the group treated with HCO dialysis at six months but not at three months.[8] Here, we report our real-life experience on nine AKI-complicated newly diagnosed MM (NDMM) patients admitted in a large primary care hospital. Baseline patient characteristics are shown in [Table 1]. All NDMM patients were in advanced disease stages; all of them received a bortezomib-based regimen in association with a prompt sFLC removal by extracorporeal techniques [Table 2].[3],[4],[10] The median time to the start of dialytic therapy from AKI presentation and the dialysis treatment duration were of four (1–20) and 13 (5–19) days, respectively. After nine HD sessions performed in 13 days, 8/9 (89%) patients achieved the renal recovery, having allowed an sFLC removal higher than 60% compared to baseline concentrations. From a hematological point of view, a complete remission, a very good partial remission, a partial remission, and a stable disease were observed in two, one, five, and one patients, respectively. With a median follow-up of 12 (2–12) months, eight (89%) patients are still alive. The overall survival was of 12 (2–12) months. We used two adsorption-based techniques to achieve a reduction in sFLC by extracorporeal therapy: HD-PMMA and HFR-SUPRA.[4],[7],[8] In our experience, we achieved favorable clinical results even in NDMM patients with poor prognostic features at the onset. Our findings, along with other center experiences,[2],[3],[4],[10] should stimulate future clinical and epidemiological researches as well as the development and selection of the best extracorporeal techniques to be used in this difficult clinical setting. This is essential to achieve the optimal outcome for these complex patients at high risk of severe clinical complications and reduced survival. Finally, our experience leads us to affirm that MM, a disease with complex pathology with multi-organ damages especially for those with renal failure, should be managed by multidiscip-linary teams with fully integrated collaboration of hematologists and nephrologists[9] for the best outcome of the patients.
Table 1: Patient characteristics.

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Table 2: Renal interventions and clinical outcomes.

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Conflict of Interest: None declared.



 
   References Top

1.
Sprangers B. Aetiology and management of acute kidney injury in multiple myeloma. Nephrol Dial Transplant 2018;33:722-4.  Back to cited text no. 1
    
2.
Menè P, Giammarioli E, Fofi C, et al. Serum free light chains removal by HFR hemodiafiltration in patients with multiple myeloma and acute kidney injury: A case series. Kidney Blood Press Res 2018;43:1263-72.  Back to cited text no. 2
    
3.
Fabbrini P, Finkel K, Gallieni M, et al. Light chains removal by extracorporeal techniques in acute kidney injury due to multiple myeloma: A position statement of the Onconephrology Work Group of the Italian Society of Nephrology. J Nephrol 2016;29:735-46.  Back to cited text no. 3
    
4.
Rousseau-Gagnon M, Agharazii M, De Serres SA, Desmeules S. Effectiveness of haemodiafiltration with heat sterilized high-flux polyphenylene HF dialyzer in reducing free light chains in patients with myeloma cast nephropathy. PLoS One 2015;10:e0140463.  Back to cited text no. 4
    
5.
Dimopoulos MA, Roussou M, Gavriatopoulou M, et al. Bortezomib-based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis. Am J Hematol 2016;91:499-502.  Back to cited text no. 5
    
6.
Niscola P, Vischini G, Tendas A,et al. Management of hematological malignancies in patients affected by renal failure. Expert Rev Anticancer Ther 2011;11:415-32.  Back to cited text no. 6
    
7.
Hutchison CA, Cook M, Heyne N, et al. European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): A randomised control trial. Trials 2008;9:55.  Back to cited text no. 7
    
8.
Bridoux F, Carron PL, Pegourie B, et al. Effect of high-cutoff hemodialysis vs. conventional hemodialysis on hemodialysis independence among patients with myeloma cast nephropathy: A randomized clinical trial. JAMA 2017;318:2099-110.  Back to cited text no. 8
    
9.
Niscola P, Caravita T, Tatangelo P, Siniscalchi A, de Fabritiis P, Palumbo R. Hematologists and nephrologists working together: Moving forward with a new integrated care model for blood-related malignancies? Blood Res 2017;52:218-9.  Back to cited text no. 9
    
10.
Pasquali S, Iannuzzella F, Corradini M, et al. A novel option for reducing free light chains in myeloma kidney: Supra-hemodiafiltration with endogenous reinfusion (HFR). J Nephrol 2015;28:251-4.  Back to cited text no. 10
    

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Correspondence Address:
Pasquale Niscola
Hematology Unit and Laboratory Medicine Unit, Saint Eugenio Hospital, Rome
Italy
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DOI: 10.4103/1319-2442.308370

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