Reduction of serum free light chains predict renal recovery

Hutchison, Colin A.

doi:10.1007/s00277-009-0836-1

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…One study assayed serial samples from 17 myeloma patients and found that serum FLC concentrations fell more rapidly in response to treatment than did intact immunoglobulin G, and correlated closely with the level of bone marrow plasma cells and serum b2 microglobulin concentrations [13]. There are also some early data that in patients with acute kidney injury due to myeloma, reducing serum FLC concentration by utilizing chemotherapy accompanied by a high cut-off dialyzer may lead to improved renal recovery [14]. Additionally, myeloma patients in whom the myeloma protein is undetectable by IFE as a consequence of therapy, who also normalize the j/k FLC ratio, have improved overall survival compared to those that do not [15].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Serum free light chain analysis

2010

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In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as j and k ''free'' LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol. 85:787-790, 2010. V V C 2010 Wiley-Liss, Inc. BackgroundHematologic malignancies frequently result in the production of monoclonal immunoglobulin. Detection of both intact immunoglobulin and immunoglobulin free light chains (FLC) in the urine and blood has proven to be valuable in the diagnosis, prognosis, and monitoring of treatment of these diseases. One particularly useful property of serum FLC is their short half-life in the blood (j, 2-4 hrs; k, 3-6 hrs) in comparison to intact immunoglobulin (21 days), which provides an opportunity for real-time monitoring of disease progression and response to treatment.For well over a century, testing for the presence of Bence Jones (BJ) protein in the urine was considered to be the gold standard to assess the clonally abnormal levels of immunoglobulin FLC. This technique can detect FLC down to the range of 10-40 mg/L; however, it can be challenging to obtain an accurate 24 hr urine collection, which is necessary for the test [1]. Moreover, due to the high resorptive capabilities of the proximal tubules of the kidney or reduced renal function, patients with low levels of FLC in the serum may not have detectable amounts in the urine [2]. Quantitative alterations of serum immunoglobulins (Igs) may result from polyclonal or monoclonal disorders. The combination of serum protein electrophoresis (SPEP), immunofixation (IFE), and densitometric analysis permits characterization and quantitation of the monoclonal immunoglobulin; however, the sensitivity of SPEP to detect FLC is poor, with a lower limit of sensitivity of 500-2,000 mg/L. Although the IFE does improve sensitivity for the detection of FLC (lower limit of sensitivity 150-500 mg/L), it is a more time-intensive assay and does not allow for quantification. Technical Aspects, Performance, and LimitationsThe development of an accurate and reproducible serum assay to determine j and k FLC concentration with high sensitivity has been a major challenge. A significant barrier to the development of the test is the fact that the unique epitope that is a marker of FLC is ''hidden'' or concealed in the conformational structure of an intact Ig. This precluded the development of a tool such as a specific antibody to detect the ''hidden epitope'' of FLC. This barrier was overcome in 2001 by Bradwell and coworkers [3], who dissociated the FLC from heavy chains and then raised polyclonal antibodies to detect the unique epitopes on j and k LC. T...

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Section: Clinical Applicationsmentioning

confidence: 99%

Serum free light chain analysis

2010

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Intensive haemodialysis using PMMA dialyser does not increase renal response rate in multiple myeloma patients with acute kidney injury

Hudier

Decaux

Haddj-Elmrabet

et al. 2017

Clinical Kidney Journal

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BackgroundIntensive haemodialysis (IHD) in addition to bortezomib-based chemotherapy might be efficient to rapidly decrease serum immunoglobulin-free light chains removal in patients with multiple myeloma (MM) and to improve renal prognosis and survival.MethodsThe aim of this retrospective multi-centre study was to compare the efficacy (renal recovery rate) of IHD and of standard haemodialysis (SHD) in patients with MM and dialysis-dependent acute kidney injury (AKI), concomitantly treated with bortezomib-based chemotherapy.ResultsWe selected 41 patients with MM and dialysis-dependent AKI, most likely due to myeloma cast nephropathy (MCN), and who were treated in eight French hospitals between January 2007 and June 2011. Patients were classified in two groups according to dialysis regimen: IHD [n = 21, with a mean of 11.3 dialysis sessions all with poly(methyl methacrylate) (PMMA) membranes for 13.2 days] and SHD (n = 20 patients, mostly three times per week, 31% with PMMA membrane). The main outcome was dialysis-independence at 3 months. At 3 months, 15 patients could stop dialysis: 8 (38.1%) in the IHD and 7 (35%) in the SHD group (P = 1). Moreover, 14 (56%) of the 25 patients who did show haematological response and only one of the 16 patients who did not were dialysis-independent (P = 0.002) at 3 months.ConclusionsThe results of this retrospective study did not show any clear renal benefit of IHD in patients with MM and MCN compared with SHD. Conversely, they underline the importance of the haematological response to chemotherapy for the renal response and patient prognosis.

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Reduction of serum free light chains predict renal recovery

Abstract: International audienc

Cited by 2 publications

References 8 publications

Serum free light chain analysis

Serum free light chain analysis

Intensive haemodialysis using PMMA dialyser does not increase renal response rate in multiple myeloma patients with acute kidney injury

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