Prolonging calcineurin inhibitor therapy post kidney allograft failure: a prospective study

The optimal immunosuppressive (IS) withdrawal strategy after kidney allograft failure remains unclear. This study evaluated the effects of prolonged calcineurin inhibitor (CNI) therapy on HLA sensitization, graft intolerance syndrome (GIS), and key clinical outcomes.

We conducted a prospective cohort study involving 90 adult patients with kidney allograft failure who were candidates for re-transplantation. Patients were divided into two groups: Rapid withdrawal group (discontinuation of all IS except low-dose prednisolone) and Prolonged CNI Group (maintenance of CNI for six months plus low-dose prednisolone). Outcomes assessed over a 12-month follow-up period included HLA sensitization, defined as an increase in calculated panel reactive antibody (cPRA) and the development of de novo donor-specific antibodies (dnDSA), GIS incidence, re-transplantation, hospitalization rates, and mortality.

No significant differences were observed between the groups regarding HLA sensitization one-year postgraft failure. A composite outcome of cPRA increase, dnDSA, and GIS did not differ between the groups. When evaluated separately, GIS occurred less frequently in the Prolonged CNI Group (4.8% vs. 23%; p = 0.015). Patients who continued CNI maintained better residual kidney function at 6 months (800 vs. 200 mL, p = 0.001) and experienced lower all-cause hospitalization rates (12% vs. 30%, p = 0.036), with comparable retransplantation and mortality rates. Graft removal and higher HLA mismatches were independently linked to increased sensitization at 12 months.

Prolonged CNI therapy for six months postallograft loss did not prevent HLA sensitization but reduced the incidence of GIS and preserved residual kidney function without increasing hospitalization or mortality.