The pathogenesis and diagnosis of acute kidney injury in multiple myeloma

Hutchison, Colin A.; Batuman, Vecihi; Behrens, Judith; Bridoux, Frank; Sirac, Christophe; Dispenzieri, Angela; Herrera, Guillermo A.; Lachmann, HJ; Sanders, Paul W.

doi:10.1038/nrneph.2011.168

Cited by 234 publications

(189 citation statements)

References 98 publications

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“…The latter is a fibrotic mediator, leading to TGF-b1 activity. The second theory involves the binding of excess FLCs to Tamm-Horsfall protein, which increases intratubular pressure, induces the reduction of the glomerular filtration rate, and enhances the aggregation of macrophages, which promote the inflammatory process [3]. In our case, no electrolytic or glucose imbalance was observed, but the pathological features revealed broad interstitial fibrosis and tubular atrophy, with infiltration of numerous macrophages.…”

Section: Discussionmentioning

confidence: 70%

“…Hypercalcemia, renal failure, anemia, and bone lesions (CRAB) are the four distinctive features of multiple myeloma. Among these factors, renal failure is the most important prognostic factor associated with patient survival [3]. Myeloma cast nephropathy caused by numerous monoclonal free light chains (FLCs) is a major phenotype involving the kidney [4].…”

Section: Introductionmentioning

confidence: 99%

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Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange

et al. 2016

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Myeloma cast nephropathy is a major complication of multiple myeloma. Recent evidence has demonstrated that the earlier induction of bortezomibbased chemotherapy with plasma exchange (PE) provides better results for kidney function and patient survival. Due to its non-selectivity, PE with albumin replacement carries the risk of fibrinogen loss, leading to bleeding. We herein report a case of successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20-year history of type II diabetes mellitus was admitted to our hospital for the evaluation of hypercalcemia, severe kidney dysfunction, and anemia. Subsequent bone marrow evaluation and renal biopsy revealed that she had multiple myeloma (IgG-j) and myeloma cast nephropathy. Ten days after admission, bortezomib-based chemotherapy with selective PE achieved rapid and thorough free light-chain (FLC) reduction; within a month, her kidney function had been recovered (creatinine level, 1.2 mg/dl). Her serum fibrinogen level was not reduced, and no bleeding complication occurred. Five months later, autologous hematopoietic stem-cell transplantation was performed successfully, and the patient's kidney function was stable (creatinine level, 1.1 mg/dl) thereafter. This case report demonstrates the importance of early induction therapy with bortezomib-based chemotherapy and PE in a patient with myeloma cast nephropathy, which is especially applicable in patients aged \65 years. In addition, it shows that selective PE is a safe and effective method of FLC removal.

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange

et al. 2016

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“…The concentration of FLC must be sufficiently high to cause the tubular obstruction in cast nephropathy. Therefore, alternative diagnosis should be considered in patients with FLC levels of ,50 mg/dl (64). A low or normal FLC concentration does not rule out MGRS-associated kidney diseases, because some can occur in very low clonal burden.…”

Section: Diagnostic Approach For Patients With Kidney Disease and An Mgmentioning

confidence: 99%

“…The first is the FLC assay. Unlike the MGRSassociated nephropathies, cast nephropathy nearly always occurs in patients with MM, and in fact, it is a myelomadefining event (14,64,65). The concentration of FLC must be sufficiently high to cause the tubular obstruction in cast nephropathy.…”

Section: Diagnostic Approach For Patients With Kidney Disease and An Mgmentioning

confidence: 99%

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

Leung

Nasr

2016

CJASN

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Monoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy-associated renal disease is suspected.

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“…Prompt identification and reduction of monoclonal FLCs by anti-myeloma therapy is vital for renal recovery and the prevention of irreversible damage [11][12][13]. Similarly, in cases where myeloma is not the cause of AKI, it is important to rule this out quickly so that patients can be referred for a kidney biopsy and further clinical investigation.…”

Section: Introductionmentioning

confidence: 99%

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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The pathogenesis and diagnosis of acute kidney injury in multiple myeloma

Cited by 234 publications

References 98 publications

Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange

Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

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

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