From the Guidelines
The recommended myeloma screen for patients with Acute Kidney Injury (AKI) should include serum and urine protein electrophoresis with immunofixation, serum free light chain assay, and a complete blood count. This comprehensive panel allows for detection of monoclonal proteins (M-proteins) and abnormal free light chains that can cause kidney damage in multiple myeloma, as supported by recent studies 1. Specifically, the serum free light chain assay is crucial as it can identify light chain myeloma that might be missed by electrophoresis alone. Additional tests should include serum calcium, creatinine, and albumin levels as part of a basic metabolic panel. If these screening tests suggest myeloma, bone marrow biopsy and skeletal imaging (preferably low-dose whole-body CT) should follow.
Early detection is critical because myeloma-related kidney injury can become irreversible if treatment is delayed, with renal impairment imposing the greatest impact on overall survival (OS) even after adjusting for other cofactors and comorbidities 1. The pathophysiology typically involves cast nephropathy from excess light chains precipitating in renal tubules, causing obstruction and inflammation. Prompt diagnosis allows for timely initiation of appropriate therapy, which may include plasmapheresis in some cases of severe light chain-mediated AKI, alongside antimyeloma treatments.
Key considerations in the management of myeloma in AKI include the potential for kidney biopsy to diagnose light chain cast nephropathy (LCCN), although this may not always be feasible 1. The use of certain antimyeloma agents, such as bortezomib, which is not renally cleared nor nephrotoxic, may be preferred in patients with AKI 1. In contrast, carfilzomib, while effective, carries a risk of renal toxicity and may be less desirable in this setting 1. Lenalidomide and pomalidomide require dose adjustments in renal impairment, with lenalidomide being renally cleared and dialyzable, and pomalidomide having a mild extension of its half-life in severe renal impairment 1.
Given the complexity of managing myeloma in the context of AKI, a multidisciplinary approach involving nephrology, hematology, and possibly other specialties is essential to optimize patient outcomes. The choice of initial therapy should be guided by the severity of AKI, the presence of other myeloma-defining events, and the patient's overall performance status, with the goal of rapidly reducing myeloma burden and preserving renal function.
From the Research
Myeloma Screen in AKI
- The myeloma screen in patients with Acute Kidney Injury (AKI) typically involves assessing serum free light chain (FLC) levels, as elevated FLC levels are a common cause of renal impairment in multiple myeloma (MM) patients 2, 3, 4.
- A rapid serum free light chain test, such as Seralite®, can accurately diagnose MM as the cause of AKI, with a κ:λ FLC ratio range of 0.14-2.02 and a serum FLC difference (dFLC) of 400 mg/L as decision points 3.
- The measurement of FLC levels is a useful screening tool in the diagnosis of cast nephropathy, a common cause of AKI in MM patients 4.
- Expert consensus recommends assessing estimated glomerular filtration rate (eGFR) using creatinine-based formulas, such as CKD-EPI or MDRD, to evaluate renal impairment in MM patients with chronic kidney disease (CKD) 5.
- For MM patients with AKI, the KDIGO AKI guidelines are recommended for evaluation, and renal biopsy may be necessary in certain cases, such as glomerular injuries or suspected immunoglobulin-associated amyloidosis (AL) or monoclonal immunoglobulin deposition disease (MIDD) 5.
Diagnostic Criteria
- A serum creatinine level >2 mg/dl has been reported in 16-33% of MM patients in various cohort studies 2.
- A creatinine clearance rate <30 ml/min was observed in 15-30% of MM patients in Western and Chinese cohorts, respectively 2.
- The κ:λ FLC ratio and dFLC levels can be used to distinguish between MM and non-MM related AKI, with a high sensitivity and specificity 3.
Treatment Options
- Bortezomib-based regimens are recommended as the basis of treatment for MM patients with renal impairment, as they do not require dosage adjustment in patients with dialysis or renal insufficiency 5.
- High-dose therapy and autologous peripheral blood stem cell transplantation can be considered as therapeutic options for MM patients with severe renal insufficiency, but require careful patient selection 5.
- Prolonged hemodialysis using high cutoff or adsorptive membranes may be effective in reducing toxic serum FLC concentrations in MM patients with AKI 6.