New data show a low likelihood of borderline and T-cell-mediated rejection (TCMR) in 1-year protocol kidney graft biopsies in stable low-risk kidney transplant recipients (KTRs) without proteinuria, donor-specific HLA antibodies (DSA), or acute rejection, investigators reported at the 2022 American Transplant Congress (ATC 2022)  in Boston, Massachusetts.

Among 1601 non-HLA-sensitized KTRs with a protocol biopsy at 1 year in the national transplant centers of Finland and Norway during 2004-2017, subclinical acute TCMR (Banff i2t2v0 or higher) occurred in 2.0% and borderline TCMR or higher (Banff i1t1 or higher) occurred in 12%.

Among 1018 KTRs with no history of acute rejection, proteinuria, or DSA, and adequate graft function at 1 year (serum creatinine less than 150 µmol/L or 1.7 mg/dL), TCMR was detected in only 0.1% and subclinical TCMR or higher in only 5.1% at 1 year, Ilkka Helanterä, MD, PhD, of Helsinki University Hospital in Finland, reported on behalf of his team.

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In contrast, among the 116 patients with de novo DSA, subclinical TCMR occurred in 9.5% and borderline TCMR or higher in 34%. Half of patients with de novo DSA experienced a previous acute rejection.

Among all 355 patients with acute rejection within the first year (prior to the protocol biopsy), TCMR occurred in 7.9% and borderline TCMR or higher in 32%.

Among the 115 patients with proteinuria of more than 10 mg/dL, TCMR occurred in 4.3% and borderline TCMR or higher in 22%. Among 248 patients with suboptimal graft function (serum creatinine exceeding 1.7 mg/dL), TCMR occurred in 3.6% and borderline TCMR or higher in 20%.

“Whether the detected incidence of TCMR (including borderline) justifies taking protocol biopsies in all patients, or only in targeted patients, has to be evaluated based on local practices and circumstances,” Dr Helanterä said in an interview.

A recent study published in the American Journal of Transplantation found that even borderline TCMR correlates with graft loss. Following a first TCMR event, persistent or subsequent TCMR events later occurred in at least half of recipients. Dr Helanterä said he believes transplant centers should have standard practices to deal with TCMR findings in the biopsies.

An optimal treatment regimen for TCMR has yet to be defined. In a systematic review and meta-analysis published in the American Journal of Transplantation, Julie Ho, MD, of the University of Manitoba in Winnipeg, Canada, and colleagues foundthat TCMR treatment varied.

“While pulse steroids and enhanced maintenance immunosuppression are mainstays of TCMR therapy, the low observed histological response rates and known complications of high dose glucocorticoids suggest that improved TCMR management strategies and RCTs evaluating novel drugs for TCMR treatment are urgently required,” Dr Ho’s team wrote.

References

Helanterä I, Dörje C, Ortiz F, et al. Very low frequency of pathological findings in one-year protocol biopsies of low-risk kidney transplant recipients – results from the Nordic protocol biopsy study [abstract]. Am J Transplant. 2022; 22 (suppl 3). Presented at: ATC 2022 meeting; June 4-8; Boston, Massachusetts. Abstract 210.

Rampersad C, Balshaw R, Gibson IW, et al. The negative impact of T cell–mediated rejection on renal allograft survival in the modern era. Am J Transplant. 2022 Mar;22(3):761-771. doi:10.1111/ajt.16883

Ho J, Okoli GN, Rabbani R, et al. Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis. Am J Transplant. 2022 Mar;22(3):772-785. doi:10.1111/ajt.16907