Subclinical inflammation phenotypes and long-term outcomes after pediatric kidney transplantation

Abstract

The implementation of surveillance biopsies in pediatric kidney transplantation remains controversial. Surveillance biopsies detect subclinical injury prior to clinical dysfunction, which could allow for early interventions that prolong allograft survival. We conducted a single-center retrospective cohort study of 120 consecutive pediatric kidney recipients, of whom 103 had surveillance biopsies ≤6 months posttransplant. We tested the hypothesis that subclinical inflammation (borderline or T cell-mediated rejection without clinical dysfunction) is associated with a 5-year composite endpoint of acute rejection and allograft failure. Overall, 36% of subjects had subclinical inflammation, which was associated with increased hazard for the composite endpoint (adjusted hazard ratio 2.89 [1.27, 6.57]; P < .01). Subjects with treated vs untreated subclinical borderline rejection had a lower incidence of the composite endpoint (41% vs 67%; P < .001). Subclinical vascular injury (subclinical inflammation with Banff arteritis score > 0) had a 78% incidence of the composite endpoint vs 11% in subjects with no major surveillance abnormalities (P < .001). In summary, we showed that subclinical inflammation phenotypes were prevalent in pediatric kidney recipients without clinical dysfunction and were associated with increased acute rejection and allograft failure. Once prospectively validated, our data would support implementation of surveillance biopsies as standard of care in pediatric kidney transplantation.

The clinical and pathological significance of borderline T cell–mediated rejection

“…16 Renal functional recovery was incomplete in 46.3% by 1 month after BL-R, influenced by initial serum creatinine level, but remained persistently abnormal between BL-R and A-TCMR levels, as reported by others. 9,11,12,26,28,29 We found that BL-R (and A-TCMR) provoked a broadened alloimmune response that involved dnDSA with tissue interaction by sequential histology. Failed functional recovery after BL-R occurred in 25% to 58%, 8,9 and was predicted by creatinine levels, IF/TA, and chronic vascular scores, 8 within 40 days, 18 echoing other studies.…”

“…22 Immune-mediated tubular damage was commonly observed at the time of BL-R index biopsy, 19,20,[23][24][25][26] within 40 days, 18 echoing other studies. 9,11,12,26,28,29 We found that…”

“…12,17,20,28,29 Clinical trials report mixed results for treatment of subclinical rejection, with modest benefits and reduced prevalence of BL-R. 17,[19][20][21]32 A survey of Canadian clinicians reported that 36% 12,17,20,28,29 Clinical trials report mixed results for treatment of subclinical rejection, with modest benefits and reduced prevalence of BL-R. 17,[19][20][21]32 A survey of Canadian clinicians reported that 36%…”

“…Objective evidence that the BL-R phenotype signifies biological rejection includes increased rates of the following: (1) allograft failure, and is reported in some [11][12][13] but not all studies. 14 We refute the assertion that BL-R is a clinically inconsequential category that should be eliminated from the Banff schema, 15 but instead argue for its retention with caveats applicable to individual biopsy interpretation.…”

“…Untreated subclinical inflammation in protocol BL-R persisted or worsened in 38.4% using repeat histology, as consistent with other studies. 12,17,20,28,29 Clinical trials report mixed results for treatment of subclinical rejection, with modest benefits and reduced prevalence of BL-R. 17,[19][20][21]32 A survey of Canadian clinicians reported that 36%…”