811 - Early Subclinical Renal Allograft Rejection: Graft and Patient Survival Varies by Severity and Recipient Age

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Author Block: M. D. Stegall¹, N. Singh¹, M. H. Nizam¹, B. Smith¹, C. Schinstock¹, A. Bentall², M. D. Stegall³, ¹Mayo Clinic, Rochester, MN, ²Transplant Nephrology, Mayo Clinic, Rochester, MN, ³Transplant Center, Mayo Clinic, Rochester, MN
*Purpose: This study aimed to determine the impact of early subclinical cellular rejection on KTx outcomes by severity of rejection and recipient age with a specific interest in the utility and potential risks of treating borderline subclinical rejection.
*Methods: We retrospectively examined all 4-month surveillance/protocol biopsies obtained at our center from 2006 to 2020 from solitary organ conventional transplant recipients and correlated rejection severity with death-censored graft survival at 5 years stratified by recipient age (average follow-up 8.5 ± 4.3 years). Borderline rejections were treated with IV solumedrol or high dose steroids in 80% of the cases. All rejections greater than borderline (i.e. Acute Cellular Rejection, ACR) were treated with either IV solumedrol or Thymoglobulin (2A and above).
*Results: Of the 1893 patients biopsied, 1034 were <55 years old at KTx, 522 55.0-64.99 years and 337 >65 years. At 4 months, 1723 patients had no rejection (91%), 70 (3.7%) had borderline rejection, 86 (4.5%) had ACR and <1% had AMR. Outcomes of rejection and mortality at 5 years varied by recipient age (Table).
Borderline rejection was not associated with any 5 year graft losses in the 55-65 and >65 age groups. Both groups had significantly higher 5 year mortality compared to the <55 age group (31.6% and 18.2% vs 2.5%; p<0.001 and 0.050, respectively). ACR at 4 months was associated with a 25% 5 year graft loss rate in the <55 group and 5.3% in the >65 group (p<0.067). However, death with function was significantly higher in the >65 ACR group compared to the <55 group (15.8 vs 2.3%; p<0.043).
*Conclusions: In older KTx recipients, early subclinical borderline rejection has minimal impact on graft survival and its treatment may contribute to mortality. In contrast, in younger patients both ACR and borderline rejection are associated with decreased graft survival without higher mortality. These data suggest that studies aimed to improve graft survival by decreasing rejection might best be limited to younger recipients. In addition, a randomized trial of treatment vs non-treatment of borderline rejection in older recipients is needed to assess treatment-related mortality within this cohort.