Use of immunotherapy such as CTLA-4 and PD-1 inhibitors have been sparingly used in renal transplant patients due to the concern for rejection. Several cases and one recently published in NEJM last year showed severe acute cellular and antibody mediated rejection with use of PD-1 inhibitor therapy. In the limited number of patients who have received these agents, it appears that PD-1 inhibitors could be more prone than CTLA-4 antagonists to cause rejection in the transplanted kidney. This is especially true when the patients receive anti–CTLA-4 agents before PD-1 inhibitor treatment.
We reported now in NEJM a creative solution of preventing rejection in a patient getting nivolumab (PD-1 inhibitor). By using a prophylactic approach of higher doses of steroids and mTOR inhibitors, we were able to successfully prevent rejection along with successful treatment of the cancer as noted in the supplementary files of the letter. Immune check point inhibitors have revolutionized the treatment of many types of cancers.With this approach, it is possible that these agents can be perhaps safely be used in the organ transplant patient.
We recently reviewed entire literature on the use of immunotherapy in the organ transplant world. As stated above, the rejections were mostly seen in PD-1 inhibitor based therapy compared to CTLA-4 therapy. In addition, the 2 cases of liver transplant where these agent were used and 1 case of heart transplant didn’t lead to a rejection episode. But in the renal transplant patients, 5 cases have now been reported of leading to acute cellular and antibody mediated rejection when PD-1 inhibitor was administered. The above NEJM case suggests a potential treatment strategy.
Renal effects of immunotherapy are not minor. AIN, podocytopathy and electrolyte disorders have been reported. It is important for the general nephrologists to know about these effects.Two recent reviews discuss this elegantly.