Highly Human Leukocyte antigen sensitized patients have relatively fewer chances of being transplanted successfully and may remain dialysis dependent for a long time. In the last few years with the development of immunomodulatory therapies and advancements in immunological investigations, the chance s of transplantation in these sensitized patients have improved. Desensitization therapies in these patients include plasma exchange, intravenous immune globulins and immunomodulatory agents such as rituximab and bortezomib. These agents used together in desensitization protocols across the world have shown encouraging results in highly Human Leukocyte Antigen sensitized recipients awaiting renal transplant. We used a desensitization protocol using rituximab followed by bortezomib with concurrent plasma exchange sessions and Intravenous Immune Globulins. Our aim was to assess improvement in renal function and quality of life in these patients after desensitization and renal transplantation. To the best of our knowledge, this is the first account of desensitization prior to renal transplantation from Pakistan.