Patients with multiple myeloma have excellent long‐term outcomes after recovery from dialysis‐dependent acute kidney injury

Yadav, Punit; Hutchison, Colin A.; Basnayake, Kolitha; Stringer, Stephanie; Jesky, Mark; Fifer, Lesley; Snell, Kym I E; Pinney, Jennifer H.; Drayson, Mark T.; Cook, Mark; Cockwell, Paul

doi:10.1111/ejh.12644

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…There are significant health and social implications associated with long term RRT, including increased frequency of infection, reduced quality of life and financial pressures (Berman et al, 2004). Unlike cast nephropathy, MGRS patients do not appear to demonstrate the same ability to recover renal function (Yadav et al, 2016), with three of the four patients who were on RRT at the time of diagnosis remaining on RRT for the duration of the study. Similar to multiple myeloma with renal impairment, progression to RRT and renal failure limits chemotherapy treatment options in the event of disease relapse.…”

Section: Discussionmentioning

confidence: 96%

“…Depth of haematological response appears to improve renal surviva (RS) (Rajkumar et al , ), but limited numbers of patients received novel anti‐plasma cell agents, such as thalidomide and bortezomib in these series. MGRS lesions, cast nephropathy and renal immunoglobulin light chain (AL) Amyloidosis have previously been reported and were therefore excluded from this retrospective study (Wechalekar et al , ; Yadav et al , ).…”

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confidence: 99%

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Long term outcomes in monoclonal gammopathy of renal significance

Khera

Panitsas²,

Djebbari

et al. 2019

Br J Haematol

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Summary Unlike AL amyloid and cast nephropathy, the long‐term outcomes of monoclonal gammopathy of renal significance (MGRS) patients with other renal histopathologies remain unclear. It is uncertain if early intervention improves renal outcomes, because of a lack of evidence from prospective studies. In this retrospective study, we examined outcomes of 41 MGRS patients treated between 2004 and 2017 across five centres: four in the UK and one in the Republic of Ireland. The primary outcome measure was renal survival estimated by Kaplan–Meier product‐limit method. Thirty‐three patients (80·5%) were kappa light chain (LC) restricted. Twenty‐seven patients (65·9%) presented with LC deposition disease on renal histology. At 24 months follow‐up, estimated renal survival was 81·6% for the whole cohort. The estimated overall survival was 80·3% at 48 months. At 24 months, patients who had chronic kidney disease (CKD) stage 2–3b at diagnosis showed an estimated renal survival of 100% compared to 80·7% in those with CKD stage 4–5 at diagnosis (P = 0·04). Poorer outcomes in MGRS patients were historically attributed to delayed diagnosis due to small plasma cell clones, as well as the need for renal biopsy.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Long term outcomes in monoclonal gammopathy of renal significance

Khera

Panitsas²,

Djebbari

et al. 2019

Br J Haematol

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“…It is important to consider for future clinical studies that renal insufficiency could be a contraindication for usage of PAA in MM patients. Renal impairment is a common complication of MM (50%) and up to 5% require dialysis (Yadav et al, 2016a, Yadav et al, 2016b). The clinical toxicity is probably from oxalate, an end-product of ascorbate metabolism.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Xia

Zhang

et al. 2017

EBioMedicine

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High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138+ MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients. PAA alone or in combination with melphalan inhibits tumor formation in MM xenograft mice. This study shows PAA efficacy on primary cancer cells and cell lines in vitro and in vivo.

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“…Yadav et al shown that the median time to death in these patients was 5.1 months [31]. It is important to highlight that an early initiation of hemodialysis and prompt hemodialysis may improve the outcome [30].…”

Section: Discussionmentioning

confidence: 96%

“…In a single-center study, renal recovery was associated with effective treatment of MM and a sustained reduction in the concentration of the involved FLC clone. The majority of patients who recover renal function have no further need for dialysis [31]. It has been described that the median overall survival in people who recovered renal function was 62.4 [32] -64.1 [31] months.…”

Section: Discussionmentioning

confidence: 99%

Hemodiafiltration with ultrafiltrate regeneration reduces free light chains without albumin loss in multiple myeloma patients.

Mier

Ojeda

Alvarez‐Lara

et al. 2020

Preprint

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Background Acute kidney injury (AKI) occurs in 12-20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss. Hemodiafiltration with ultrafiltrate regeneration is a technique that includes a process of adsorption. The aim of this study was to evaluate the effectiveness of hemodiafiltration with ultrafiltrate regeneration in reducing FLC levels without causing albumin loss.Methods This is an observational study (2012 to 2018) including eleven patients with MM (6 kappa, 5 lambda) and AKI. All patients were treated with chemotherapy and hemodiafiltration with ultrafiltrate regeneration. Blood Samples (pre and post-dialysis) and ultrafiltrate were collected pre and post-resin at 5 minutes after initiation of the session and 5 minutes before the end of the procedure. ResultsThe serum levels of kappa and lambda were reduced by a 53±14% and 33±22% respectively.Serum albumin concentration remained unchanged after the procedure. In the ultrafiltrate, the mean FLC reduction ratio shortly after initiation of the dialysis procedure was: 99.2% and 97.06% for kappa and lambda respectively, and only 0.7% for albumin; and at the end of the session the percent reduction was: 63.7% and 33.62% for kappa and lambda respectively, and 0.015% for albumin.Patients clinical outcome was: 36.4% recovered renal function, 18.2% died during the first year and 45.45% required maintenance dialysis.Conclusions Hemodiafiltration with ultrafiltrate regeneration reduces FLC levels without producing a significant loss of albumin; and, FLC removal is maintained throughout the session. Therefore, hemodiafiltration with ultrafiltrate regeneration may be considered an effective adjunctive therapy in patients with MM.

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Patients with multiple myeloma have excellent long‐term outcomes after recovery from dialysis‐dependent acute kidney injury

Cited by 25 publications

References 29 publications

Long term outcomes in monoclonal gammopathy of renal significance

Long term outcomes in monoclonal gammopathy of renal significance

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid

Hemodiafiltration with ultrafiltrate regeneration reduces free light chains without albumin loss in multiple myeloma patients.

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