Kidney Injury Associated with Monoclonal Gammopathy: A Nephrologist's Perspective

Monoclonal gammopathies (MG) represent a group of haematological conditions resulting from excessive monoclonal immunoglobulin (MIg) production by abnormal clonal proliferation of plasma cells or B cells. The diseases can range from malignant conditions such as multiple myeloma and B-cell lymphoproliferative disorders to non-malignant monoclonal gammopathy of undetermined significance. The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe kidney damage in the absence of myeloma-defining events or other haematological malignancies. The clones in MGRS are usually small and low-grade but can cause kidney damage due to the nephrotoxic MIg. There is a wide spectrum of kidney injury caused by the MG with MIgs causing nephrotoxicity either via direct deposition onto various parts of the kidney or indirect mechanisms through the autoantibody activity or dysregulation of the complement alternative pathway. The diagnosis of MIg-associated kidney diseases remains challenging due to its complexity and heterogeneity. Prognosis depends on accurate diagnosis of both kidney lesions and the underlying haematological diseases with early initiation of treatment. Clone-directed therapy has now become the cornerstone for the management of this disorder. Various therapeutic agents including proteasome inhibitors, monoclonal antibodies, immunomodulatory drugs, chimeric antigen receptor T-cells and Bruton tyrosine kinase inhibitors have been used to manage patients with MG and kidney diseases. Further clinical research and close collaboration between nephrologists, pathologists and haematologists can help to improve the prognosis of these patients.