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

Hutchison, Colin A.; Heyne, Nils; Airia, Parisa; Schindler, Ralf; Zickler, Daniel; Cook, Mark; Cockwell, Paul; Grima, Daniel

doi:10.1093/ndt/gfr773

Cited by 115 publications

(107 citation statements)

References 16 publications

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“…This is an important observation, given that earlier data, in smaller numbers of patients, suggested that only about a third of patients could discontinue dialysis [12][13][14][15]. Our results should be carefully compared to the results obtained with the use of HCO dialysis, since with extended HCO dialysis up to 70% may become dialysis independent [16,17]. The results of the prospective randomized trials (EuLITE, NCT00700531 and MYRE, NCT01208818) will define the role of mechanical means for the management of patients with MM and cast nephropathy requiring dialysis, but, in both studies, VD-based therapy is the backbone.…”

Section: Discussionmentioning

confidence: 55%

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

et al. 2016

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Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR < 30 ml/min/1.73 m 2 ), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P 5 0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level 11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response.

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Section: Discussionmentioning

confidence: 55%

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

et al. 2016

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“…One such approach involves the use of extended dialysis sessions for patients with myeloma cast nephropathy using a dialyzer cartridge with pores of sufficient size to allow the removal of light chains. Pooling data from multiple centers, Hutchison et al (57,94) showed that nearly three quarters of dialysis-dependent patients receiving this therapy recover renal function and that this recovery is predicted by the degree of light chain reduction and a shorter time between presentation and initiation of light chain-removing dialysis (94 …”

Section: Plasmapheresis and Other Extracorporeal Techniques To Removementioning

confidence: 99%

Kidney Disease and Multiple Myeloma

Heher

Rennke

Laubach

et al. 2013

Clinical Journal of the American Society of Nephrology

146

122

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SummaryKidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve.

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“…In a previous investigation of myeloma patients presenting with AKI at diagnosis who underwent a renal biopsy, the principal pathology in nearly 90% of patients was cast nephropathy as a consequence of excess and nephrotoxic monoclonal FLCs [25]. Therefore, myeloma patients with severely reduced kidney function present with high sFLC levels as the direct cause in almost all cases.…”

Section: Discussionmentioning

confidence: 97%

Multiple Myeloma Can Be Accurately Diagnosed in Acute Kidney Injury Patients Using a Rapid Serum Free Light Chain Test

Drayson

Heaney

Campbell

et al. 2017

Clinical Lymphoma Myeloma and Leukemia

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Background: Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI. Method: sFLCs were retrospectively analysed in patients with AKI stage 3 as per KDIGO criteria (i.e. serum creatinine ≥354 μmol/L or those on dialysis treatment) (n = 99); 45/99 patients had a confirmed MM diagnosis. Results: The Seralite® κ:λ FLC ratio accurately diagnosed all MM patients in the presence of AKI: a range of 0.14-2.02 returned 100% sensitivity and specificity for identifying all non-myeloma related AKI patients. The sFLC difference (dFLC) also demonstrated high sensitivity (91%) and specificity (100%): an optimal cut-off of 399 mg/L distinguished between myeloma and non-myeloma AKI patients. We propose a pathway of patient screening and stratification in unexplained AKI for use of Seralite® in clinical practice, with a κ:λ ratio range of 0.14-2.02 and dFLC 400 mg/L as decision points. Conclusions: Seralite® accurately differentiates between AKI due to MM and AKI due to other causes in patients considered at risk of myeloma. This rapid test can sensitively screen for MM in patients with AKI and help inform early treatment intervention.

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

Abstract: 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.

Cited by 115 publications

References 16 publications

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

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

Kidney Disease and Multiple Myeloma

Multiple Myeloma Can Be Accurately Diagnosed in Acute Kidney Injury Patients Using a Rapid Serum Free Light Chain Test

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