MULTIPLE MYELOMA (P KAPOOR, SECTION EDITOR) Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney—What We Know and What the Future May Hold Sandhya Manohar 1 & Samih H. Nasr 2 & Nelson Leung 1,3 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Purpose of review To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephrop- athy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event. Recent findings The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. Summary FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein. Keywords Cast nephropathy . Plasma cell dyscrasia . Multiple myeloma . Light chains . Myeloma kidney . Acute kidney injury Introduction It was during the 1840s when Bence Jones proteins were initially described by the famous medical chemist/physician Henry Bence Jones [1]. It took nearly another 75 years for the earliest description of cast nephropathy to be published by Thannhauser and Krauss [2]. Along the way, there were discoveries and con- tributions by many curious researchers that have enhanced our knowledge of this disease. This knowledge has greatly improved our ability to care for patients with plasma cell dyscrasias. These hematological diseases responsible for light chain cast nephropathy are characterized by the clonal expansion of abnor- mal plasma cells (and occasionally B cells) which in turn produce large amounts of monoclonal proteins. The kidney due to its intrinsic function as a filtering organ faces the brunt of the injury with protein deposition, inflammation, and subsequent renal fail- ure. There is a wide spectrum of renal lesions associated with plasma cell dyscrasias. This is due to differences in renal han- dling of these proteins at various segments of the nephron and properties that are intrinsic to the protein being processed. Importantly, a number of these lesions occur in patients even in the pre-malignant state where chemotherapy initiation would not have been indicated, but the growing awareness of progressive renal damage has led to the need for the new terminology mono- clonal gammopathy of renal significance (MGRS) to emphasize the need for early recognition and treatment [ 3]. Light chain cast nephropathy is not MGRS as a large burden of light chains is required to cause this complication, and it is typically seen in malignant diseases. The updated 2014 criteria of International Myeloma Working Group (IMWG) consider acute renal failure by light chain cast nephropathy as a myeloma defining event [4]. It is also the most common renal lesion seen in multiple myeloma. However, it has also been associated with Waldenström macroglobulinemia [5], other lymphomas [6], and chronic lymphocytic leukemia [7]. This article is part of the Topical Collection on Multiple Myeloma * Nelson Leung leung.nelson@mayo.edu 1 Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA 2 Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology and Pathology Mayo Clinic, Rochester, MN, USA 3 Department of Internal Medicine, Division of Hematology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55901, USA Current Hematologic Malignancy Reports https://doi.org/10.1007/s11899-018-0451-0