Light-Chain Deposition Disease (LCDD) frequently recurs after renal transplantation, displaying a pernicious course. Herein we have described a 39-year-old Caucasian man with a history of immunoglobulin G-kappa multiple myeloma who failed two chemotherapy regimens, but ultimately responded to the combination of thalidomide, bortezomib, and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation 3 years prior to transplantation, during which time he showed no evidence of persistent or recurrent disease. At 3 days following spousal living related renal transplantation, he displayed a rapid deterioration of renal function requiring dialysis therapy. This episode failed to respond to empiric antirejection therapy including anti-thymocyte globulin, plasmapheresis, and anti-CD20 monoclonal antibody. Increasing evidence suggested recurrence of LCDD, including positive immunofluorescence staining of basement membranes and vessels for kappa light chains as well as free kappa light chains in his urine and serum. Following suspension of sirolimus, he was initiated on and responded to bortezomib (1.3 mg/m(2)) with discontinuation of dialysis within 3 weeks and progressively improving renal function. His maintenance therapy, in addition to six 2-week-long cycles of bortezomib separated by 1-week rest periods, includes cyclosporine (50 mg twice daily), prednisone (10 mg daily), and curcumin (9 g daily). In sum, bortezomib rescue therapy salvaged a spousal renal transplant afflicted with recurrent LCDD.