Myeloma Cast Nephropathy

Abstract

Myeloma cast nephropathy (MCN) is the sine qua non renal lesion of multiple myeloma (MM). It was first reported in 1909, some 60 years after the description of Bence Jones protein [1]. Studies have now confirmed Bence Jones protein to be the same as monoclonal immunoglobulin free light chain (FLC) [2]. The term “cast nephropathy” was first used by Oliver in 1945 to describe the intraluminal obstruction of renal tubules by monoclonal FLC casts and the resulting inflammatory reaction around these tubules. Other than rare incidences where MCN can be the result of a lymphoplasmacytic lymphoma, it is always associated with the MM [3]. While other renal lesions can be seen with low-grade plasma cell dyscrasias, lymphoproliferative disorders, and MM, the development of MCN signifies the progression of monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) to symptomatic multiple myeloma (MM) [4].

Even though cast nephropathy is the signature lesion of MM, it is not defined in the CRAB (hyperCalcemia, Renal impairment, Anemia and Bone lesions) criteria. Renal involvement is defined as a serum creatinine (Scr) of >2 mg/dL attributable to the plasma cell dyscrasia [5]. Because several other lesions may be responsible for the renal impairment in MM, the criterion is made general to encompass all causes [6]. Unfortunately, this has also made it more difficult to study cast nephropathy as patients enrolled in some trials had only acute renal failure with MM but not necessarily MCN. Currently, the only method capable of accurately diagnosing MCN is a kidney biopsy. In practice, this is not always feasible as patients may be anticoagulated or have coagulopathy. It is therefore important to keep this in mind when interpreting studies that involve MM patients with renal impairment as a percentage of these patients may not have MCN which may impact the results.