Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

Abstract

CNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

Effect of mechanistic target of rapamycin inhibitors on postrenal transplantation malignancy: A nationwide cohort study

“…Recent meta‐analysis and literature reviews provided the evidence that early withdrawal of CNI and introduction of mTORi might induce the de novo glomerulonephritis and graft loss . However, the Cochrane database reported that mTORi might increase the acute rejection, but the effect on long‐term graft loss was still uncertain . From our result, the percentage of reentry of dialysis in the mTORi users is similar to the patients with mTORi nonusers.…”

“…It is interesting that the percentage of comorbidities such as hypertension, diabetes mellitus, ischemic heart disease, and cerebrovascular disease was higher in the mTORi users. In contrast to CNI, the nephrotoxicity and hypertension were less common in the mTORi users, and pretransplantation comorbidities might influence the clinicians’ decision in choosing the immunosuppressive agents. Hyperglycemia and hyperlipidemia were linked to the mTOR inhibitors, but Lamming et al reported that mTORi provided longevity beyond the insulin resistance.…”

“…In our database, the percentage of acute rejection was higher in the mTORi users. Although mTOR inhibitors provided antineoplastic effect in preventing malignancy, it has been noticed that the avoidance of CNI increased the rate of rejection and graft dysfunction . The chronic antibody‐mediated rejection after sustained exposure to mTORi might influence the graft survival .…”

“…Because it governs the cell proliferation and survival, the genetic alternation or mutation of mTOR signaling is a mechanism of carcinogenesis for treating metastatic renal cell carcinoma, breast cancer, or other hematopoietic malignancy . In comparison with CNI, mTOR inhibitors provide less incidence of direct nephrotoxicity, and therefore, early withdrawal of CNI has been a choice in renal transplantation recipients . Mathews et al reported that after early withdrawal of cyclosporin (CsA), mTOR inhibitors lowered the incidence of skin cancer as a maintenance therapy after transplantation.…”

“…Among the post-transplantation complications, posttransplantation malignancy is an important complication influencing the graft survival and overall survival. 4 Among these risk factors, the dysfunction of immune surveillance by immunosuppressive agents is proposed as a contributing factor. 5 Calcineurin inhibitor-based regimen is the mainstream immunosuppressive agent in renal transplantation.…”