Quadruple Immunosuppression in Kidney Transplantation: A Dual-purpose Strategy for Rejection Control and Renal Protection
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Background: Calcineurin inhibitor (CNI) nephrotoxicity and rejection risk represent competing therapeutic imperatives in kidney transplantation. Standard CNI minimization protocols carry 15%–25% rejection rates in high-risk recipients. We evaluated whether quadruple immunosuppression (reduced-dose tacrolimus, everolimus, mycophenolate mofetil [MMF], and prednisolone) could simultaneously enhance rejection control and reduce CNI nephrotoxicity. Methods: This prospective single-center pilot study enrolled 19 adult kidney transplant recipients escalated to quadruple immunosuppression (September 2022–June 2025) for two indications: (1) steroid-resistant acute rejection or high rejection-recurrence risk with concurrent benefit of CNI dose reduction (n = 7, 36.8%), and (2) CNI toxicity, delayed graft function, or high immunological risk (ABO-incompatible, deceased donor) requiring robust immunosuppression despite CNI reduction (n = 12, 63.2%). Tacrolimus dose was reduced by approximately 50% with everolimus introduction. Combined tacrolimus–everolimus trough targets were 8–10 ng/mL (acute phase) and 4–6 ng/mL (maintenance). Results: Over a median follow-up of 213 days (interquartile range: 41–411), patient and graft survival were 100%. No biopsy-proven acute rejection occurred on quadruple therapy (0/19). Mean estimated glomerular filtration rate (eGFR) improved from 37.9 ± 10.2 to 52.2 ± 12.8 mL/min/1.73 m2 at 1 month (+37.6%, P < 0.001), sustained through 12 months. Therapy was discontinued in 4/19 patients (21.1%); two developed biopsy-proven rejection after MMF cessation, responding to therapy resumption. No cytomegalovirus viremia or BK nephropathy occurred on regular viral surveillance. Conclusion: In carefully selected high-risk recipients, quadruple immunosuppression achieved 100% patient and graft survival, zero on-therapy acute rejection, and sustained eGFR improvement of 37.6% at 1 month through 12 months, warranting multicenter validation.
Institution: Yashoda Hospital
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7214769323