Serum free light chain levels and renal function at diagnosis in patients with multiple myeloma

Yadav, Punit; Cockwell, Paul; Cook, Mark; Pinney, Jennifer H.; Giles, Hannah; Aung, Y.S.; Cairns, David A.; Owen, Roger G.; Davies, Faith E.; Jackson, Graham; Child, J. Anthony; Morgan, Gareth J.; Drayson, Mark T.

doi:10.1186/s12882-018-0962-x

Cited by 31 publications

(37 citation statements)

References 23 publications

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“…The IMWG in their recent revised diagnostic criteria for MM included RI caused by MCN as a myeloma defining event, where MCN was characterised by the presence of typical histological features or an involved Table 2 Landmark analysis of associations between haemodialysis independence and overall survival in patients with MCN (n = 69). 15 . Importantly this study showed that patients could have a very high FLC level and no RI at diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…The IMWG associated RI as a consequence of MCN to a serum FLC level above 1500 mg/ L 13 , whereas the International Kidney and Monoclonal Gammopathy (IKMG) Research Group proposed a serum FLC level above 500 mg/L 14 . We recently analysed the Myeloma IX study and found that an FLC level above 800 mg/L had the highest sensitivity and specificity for severe RI defined by an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m 2 at diagnosis 15 . However that study did not include patients who required dialysis and information on renal histology was not available.…”

Section: Introductionmentioning

confidence: 99%

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Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

et al. 2020

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Myeloma cast nephropathy (MCN) is a common cause of severe renal impairment in multiple myeloma (MM). The level of free light chain (FLC) that causes MCN varies substantially and there is uncertainty about the threshold level that should be used to inform clinical practice. In a multicentre cohort study of 103 patients with a diagnosis of MM and biopsy-confirmed MCN made between 2002-2014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite®) and we explore the relationship between serum FLC level at diagnosis with renal outcome and patient survival. Using a landmark approach, overall survival (OS) was compared between patients who achieved independence from dialysis compared to those who remained dialysis dependent at 3-month, 6-month, 9-month, and 12-month time points. The median serum FLC level at diagnosis was 7531 mg/L (range 107-114600). Serum creatinine was 535 μmol/L (range 168-2993) and eGFR 7 ml/min/1.73 m 2 (range 1-34). Six patients (5.8%) had an FLC level <1500 mg/L, which is the International Myeloma Working Group threshold for MCN and two patients were below the International Kidney and Monoclonal Gammopathy working group threshold of 500 mg/L; one was hypercalcaemic, and one had high-normal serum calcium level and had received a non-steroidal anti-inflammatory agent. Sixty-nine (67%) patients required haemodialysis treatment of whom 36 (52.1%) recovered independent renal function. Sixty-six (64%) patients died with a median OS of 2.5 years (95% CI 1.8-3.3). A landmark analysis revealed that independence from dialysis was associated with improved survival at 3months (P = 0.003), 6-months (P = 0.035) and 9-months (P = 0.014); there was no survival benefit observed beyond 12 months (P = 0.146). Serum FLC level at diagnosis was neither associated with renal function recovery nor with OS. This is the largest reported cohort of patients with biopsy-confirmed MCN and prospectively measured serum FLC levels. These results indicate that a serum monoclonal FLC > 500 mg/L should be considered the threshold level associated with the development of MCN.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

et al. 2020

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“…47 Factors that promote the formation of intratubular casts include volume depletion, metabolic acidosis, loop diuretics through the increase in tubular sodium concentration, increased urinary calcium and hypercalcemia, and radiocontrast media. 48 Sensitive assays for plasma FLCs as well as serum and urine protein electrophoresis and immunofixation facilitate the diagnosis of myeloma-related AKI. The normal plasma-free κ-to-λ ratio is 0.26 to 1.65 in patients without kidney impairment and 0.37 to 3.1 in patients with severe kidney impairment.…”

Section: Light-chain Cast Nephropathymentioning

confidence: 99%

“…The normal plasma-free κ-to-λ ratio is 0.26 to 1.65 in patients without kidney impairment and 0.37 to 3.1 in patients with severe kidney impairment. 48 Elevated FLCs in association with an abnormal κ-to-λ ratio typically indicate a monoclonal plasma cell proliferative process. The plasma FLC assay is more sensitive than urine protein electrophoresis for detecting FLCs.…”

Section: Light-chain Cast Nephropathymentioning

confidence: 99%

Onconephrology: The intersections between the kidney and cancer

Rosner

Jhaveri

McMahon

et al. 2020

CA A Cancer J Clinicians

101

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Onconephrology is a new subspecialty of nephrology that recognizes the important intersections of kidney disease with cancer. This intersection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, paraneoplastic glomerulonephritis, and the interactions of chronic kidney disease with cancer. Data clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened. This highlights the imperative for collaborative care between oncologists and nephrologists in recognizing and treating kidney disease in patients with cancer. In response to this need, specific training programs in onconephrology as well as dedicated onconephrology clinics have appeared. This comprehensive review covers many of the critical topics in onconephrology, with a focus on acute kidney injury, chronic kidney disease, drug-induced nephrotoxicity, kidney disease in stem cell transplantation, and electrolyte disorders in patients with cancer.

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“…Physicochemical properties of the secreted paraprotein may determine pathological features, for which a variety of Ig-dependent and independent mechanisms have been described (see Figure 1 ) [ 8 , 14 ]. However, it has to be emphasized that FLC levels >800 mg/L are good predictors of severe RI, regardless of the paraprotein type [ 16 ]. Tools to recognize the degree of nephrotoxicity for particular monoclonal paraproteins are still lacking; therefore, very early identification of renal insult is crucial.…”

Section: Multiple Myeloma and Renal Impairment—an Overviewmentioning

confidence: 99%

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

Woziwodzka

Małyszko

Batko

et al. 2020

JCM

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Multiple myeloma (MM) is a common plasma cell malignancy, which is responsible for significant mortality, often related to severe renal impairment (RI). Kidney injury can limit therapeutic choices and may often translate into poor outcomes, but it remains potentially reversible in a proportion of patients. The most accessible, conventional markers of RI are subject to several shortfalls, among which are the delayed onset following kidney insult, multiple interfering factors, and lesser sensitivity to mild changes in glomerular filtration. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have accumulated large interest in MM-RI due to being very sensitive markers of renal injury, as well as indicators of tubular-glomerular axis impairment. Of interest, recent data suggest that prediction of acute kidney injury may be aided by urinary tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), which both act to induce G1 cell cycle arrest, reflective of a state of pre-injury, and thus may be superior to other measures of kidney insult (NGAL, kidney injury molecule ((KIM-1)). Moreover, TIMP-2 seems to be a biomarker dedicated to distal tubular cells, whereas insulin-like growth factor-binding protein 7 (IGFBP7) secretion has been found in proximal tubule cells. IGFBP7 can also identify a subsection of the normal proximal nephron, even, maybe the one that is responding to insult. They may be adopted into a conceptual screening panel for MM-RI. Unfortunately, no biomarker is ideal (influence of non-renal, biologic factors), and novel measures are limited by economic constraints, availability, lack of standardization. With the emergence of more advanced diagnostic and prognostic MM models, markers reflective of disease processes (including RI) are of high interest. Candidate molecules also include peptidome markers.

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Serum free light chain levels and renal function at diagnosis in patients with multiple myeloma

Cited by 31 publications

References 23 publications

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

Onconephrology: The intersections between the kidney and cancer

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

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