Several clinical signs are associated with MGRS including declining kidney function, microscopic hematuria, proteinuria (ranging from sub-nephrotic to nephrotic syndrome range proteinuria and proximal tubular dysfunction which may present as Fanconi Syndrome. Once MGRS is suspected, it is critical to identify the monoclonal protein responsible for kidney toxicity or the cell line secreting the monoclonal protein. Usually MGRS disorders have small levels of circulating M-proteins (due to the small clonal burden of the underlying B-cell or plasma cell disorder) thus decreasing the sensitivity of serum protein electrophoresis (SPEP). Serum immunofixation electrophoresis is 10 times more sensitive than SPEP in the identification of M-proteins in MGRS. Serum protein electrophoresis, urine protein electrophoresis (UPEP), serum and urine immunofixation, serum free light chain assay, serum free light chain ratios and a bone marrow biopsy are required for the identification of the cell population secreting the pathologic monoclonal protein. A kidney biopsy should be performed in all cases of MGRS to confirm the M-protein's causal relationship with regards to kidney disease. The only exception is AL amyloidosis which can be diagnosed if AL deposits are detected in other tissues, such as peripheral fat. Overt hematologic malignancies such as multiple myeloma should be excluded.
