Introduction: Desensitization is an effective strategy to promote kidney transplantation (KT) for highly-sensitized (HS) pediatric patients with end-stage kidney disease. Here we report the evolution and outcomes from 25-years of pediatric KT at a high-volume desensitization center.
Methods: All HS pediatric renal transplants performed between January 2009 and March 2025 at Cedars-Sinai Medical Center were evaluated. HS patients were defined as calculated panel reactive antibody (cPRA) >30%. Patients underwent desensitization with intravenous immunoglobulin (IVIG) with or without plasmapheresis, rituximab, and/or Tocilizumab anti-interleukin-6 receptor monoclonal antibody (2013-2024).  Beginning 2024, Daratumumab, anti-CD38 monoclonal antibody, replaced Tocilizumab as second line therapy in difficult-to-transplant HS patients.  All patients received alemtuzumab induction therapy (15-30mg, single dose SQ at time of transplant) and were maintained on tacrolimus, mycophenolate and steroids. Available data on patients were analyzed for cPRA prior to, and following desensitization, human leukocyte antigen (HLA) mismatch, and donor specific antibodies (DSA). Serum creatinine (sCr) and incidence of rejection was evaluated post-operatively. Graft and patient survival are reported.
Results: Between 2009-2025, 31 patients received desensitization and underwent kidney transplantation at our center.  The median age at transplant was 11.5 years, and the most common etiologies of renal disease were posterior uretheral valves/obstructive uropathy (32.1%) and renal dysplasia/hypoplasia (21.4%).    Sensitization stemmed primarily from prior renal transplant (78.6%) and prior blood transfusion (42.9%).  At time of desensitization, the median Class I PRA was 64 and Class II was 71. The median time from initial desensitization to KT was 173 days (IQR 66-391 days). Living donor KT was performed in 5 (17.9%) and deceased donor KT in 23 (82.1%). At the time of KT, median cPRA at KT was 84% (IQR 51-98%) and donor-specific antibodies were identified in 15 (53.6%) of recipients. Overall, 15 (53.6%) of patients experienced rejection. At 6-months, median sCr was 0.7mg/dL, median graft survival was 360 days, and 85.7% overall graft survival for the duration of the follow-up. To date, one patient who received daratumumab was transplanted.
Conclusions: Desensitization did not significantly change cPRA scores but can result in acceptable crossmatches and decrease the waiting time for HS pediatric patients with ESRD.  Use of newer monoclonal target therapies such as tocilizumab and daratumumab have also enabled more favorable crossmatch results.  T-cell depleting agents is a mainstay approach to induction therapy, while patients are maintained on continuous triple immunosuppression post-transplant. While rejection remains a serious concern with preformed DSA as a primary risk factor, 1-year graft survival is acceptable. Continued utilization will provide additional information for analysis and promotion of desensitization in the pediatric population.