Case Presentation: An 86-year-old female with history of hypertension and endometrial cancer was admitted for acute kidney injury. On presentation, patient’s creatinine was 3.06 mg/dL, associated with a dipstick urinalysis showing proteins 100 mg/dL. She was unresponsive to intravenous fluids, demonstrated by a persistent rise in her creatinine to 3.89 mg/dL. Urine output and oral intake were adequate. Her CBC was only significant for normocytic anemia (10.6 g/dL); her electrolytes including calcium (8.8 mg/dL), phosphorus and liver enzymes were unremarkable. Imaging of the abdomen failed to show signs of chronic kidney disease, hydronephrosis or urinary retention. Studies for secondary glomerulonephritis were negative, including ANA, ANCA, and a viral hepatitis panel. Spot urine protein-creatinine ratio revealed non-nephrotic range proteinuria (2717 mg/g) without significant albuminuria as revealed by urine albumin-creatinine ratio 47 mg/g. Urine protein electrophoresis revealed proteinuria mostly comprised of Kappa light chains. Serum electrophoresis and immunofixation showed two traces of free Kappa monoclonal protein and IgG Kappa monoclonal protein in the fast and mid gamma region (<0.1 g/dl each). Serum free light chains assay revealed severely elevated Kappa light chains to 1971 mg/L (NV 3.3-19.4) with a free light chain ratio also elevated to 165.63 (NV 0.26-1.65). Given the suspicion for Multiple Myeloma, patient underwent bone marrow biopsy that was reported as plasma cell myeloma involving 60-70% of the bone marrow. Further assessment with a full body bone survey was negative. Patient started Dexamethasone and Bortezomib. Her creatinine peaked at 5.36 mg/dL prior to treatment and down trended to 2.2 mg/dL after first treatment cycle.
Discussion: Light Chain Cast Nephropathy (LCCN) is the only renal complication of multiple myeloma (MM) that is considered as a myeloma-defining event per the IMWG 2014 criteria.[1] Despite the extensive myeloma-related kidney diseases such as AL amyloidosis or immunoglobulin deposition disease, these are not considered defining events given that they can be seen in other plasma cell dyscrasias such as MGUS or smoldering myeloma.[2] Diagnosis of LCCN does not necessarily require biopsy and it is made on the basis of proving light chain monoclonality by presence of uninvolved free light chain levels (> 1500 mg/L). Usually, patients will show significant proteinuria that is not comprised predominantly by albumin. If serum free light chains (FLC) are less than 500 and there is significant albuminuria, kidney biopsy might be indicated to identify the primary cause of renal dysfunction.[2] In MM, the most common clinical manifestations are anemia, infections, hypercalcemia, lytic or osteopenic bone disease.[1,3] Our patient´s clinical presentation was mostly remarkable for acute creatinine elevation and mild normocytic anemia. The core management in patients with MM and LCCN is starting chemotherapy and also consider adjuvant supportive therapies such as apheresis or dialysis with high cut off to decrease the FLC levels.[1,2] In patients with LCCN, renal recovery is predicted by achievement of reduction of free light chains ratio by at least 90%.[4]
Conclusions: Even in the absence of other CRAB criteria, multiple myeloma should be suspected in patients with significant proteinuria. LCCN is a myeloma-defining event by itself and can be diagnosed by the presence of uninvolved free light chain levels (> 1500 mg/dL) and without the need for kidney biopsy.