Two-year protocol biopsy after kidney transplantation in clinically stable recipients - a retrospective study.

The idea of protocol biopsy is to detect subclinical pathologies, including rejection, recurrent disease, or infection for early intervention and adjustment of immunosuppressants. Nevertheless, it is not adopted by most clinicians because of its low yield rate and uncertain long-term benefits. This retrospective study evaluated the impact of protocol biopsy on renal function and allograft survival. A two-year protocol biopsy was proposed for 190 stable patients; 68 of them accepted [protocol biopsy (PB) group], while 122 did not [nonprotocol biopsy (NPB) group]. The rejection diagnosis was made in 13 patients by protocol biopsy, and 11 of them had borderline rejection. In the following 5 years, graft survival was better in the PB group than in the NPB group (P = 0.0143). A total of 4 and 17 patients in the PB and NPB groups, respectively, had rejection events proven by indication biopsy. Renal function was better preserved in the PB group than in the NPB group (P = 0.0107) for patients with rejection events. Nevertheless, the survival benefit disappeared by a longer follow-up period (12-year, P = 0.2886). In conclusion, 2-year protocol biopsy detects subclinical pathological changes in rejection and preserves renal function by early intervention so as to prolong graft survival within 5 years.

Treatment of borderline infiltrates with minimal inflammation in kidney transplant recipients has no effect on allograft or patient outcomes.

In 2005, the Banff committee expanded the "borderline changes" category to include lesions with minimal (<10%) inflammation: "i0" borderline infiltrates. Clinical significance and optimal treatment of i0 borderline infiltrates are not known. Data suggest that i0 borderline infiltrates may have a more favorable prognosis than borderline infiltrates with higher grades of interstitial inflammation. In this single-center, retrospective, observational study, we assessed 90 renal transplant recipients with i0 borderline infiltrates on biopsies indicated for graft dysfunction. We studied the impact of treatment with corticosteroids on allograft function, allograft survival, and patient survival. We found no differences between treated and untreated groups with respect to eGFR at 4 weeks and 6 months after biopsy. Follow-up biopsies, available in 67% of patients, were negative for rejection in almost half of all cases, regardless of treatment status. The frequencies of persistent borderline infiltrates (38%) and higher-grade T cell-mediated rejection (1A or greater, 14%) on follow-up biopsies were similar between the two groups. There were no differences in rejection-free allograft survival, death-censored graft failure, or patient mortality among treated vs non-treated i0 borderline patients. Our findings suggest that the natural history of i0 borderline infiltrates, in relatively low immunologic risk patients, is not affected by corticosteroid treatment.

Borderline rejection in ABO-incompatible kidney transplantation.

INTRODUCTION: The clinical results of ABO-incompatible (ABOi) and ABO-compatible (ABOc) kidney transplantation (KT) are similar. Protocol kidney biopsies (PKB) of ABOi transplant recipients show positivity for C4d without evidence of antibody-mediated rejection (ABMR), but little is known about the histologic progression. METHOD: We evaluated histologic parameters in PKB at 12 months and also compared clinical outcome at 1 year. This is a prospective observational study conducted between 2009 and 2013. We performed 146/30 ABOc/ABOi consecutive living-donor KT with PKB as well as additional indication biopsies. In the ABOi group, the desensitization protocol consisted of rituximab, plasma exchange or immunoadsorption, and immunoglobulins. RESULTS: In indication biopsies during the first year, T-cell-mediated rejection Banff ≥immunoadsorption was 8.2% vs 6.7% (P=.561) and ABMR 4.8% vs 13.3% (P=.095). At 1 year, PKB (ABOc/ABOi) showed differences in borderline rejection lesions (6.8% vs 23.3% [P=.012]) and in C4d positivity in the ABOi group (P=.001). Interstitial fibrosis and tubular atrophy (IFTA) lesions (ABOc/ABOi) were 68.4% vs 63.2% (P=.348). Transplant glomerulopathy was 0.7% vs 3.3% (P=.373) at 1 year. CONCLUSIONS: Our PKB ABOi series shows at 1 year more borderline lesions independent of ABO titers, HLA incompatibility, and the presence of antidonor antibody, but do not show more IFTA nor transplant glomerulopathy. No clinical differences were observed between ABOi and ABO transplants.

High PIRCHE Scores May Allow Risk Stratification of Borderline Rejection in Kidney Transplant Recipients.

BACKGROUND: The diagnosis of borderline rejection (BLR) ranges from mild inflammation to clinically significant TCMR and is associated with an increased risk of allograft dysfunction. Currently, there is no consensus regarding its treatment due in part to a lack of biomarkers to identify cases with increased risk for immune-mediated injury. METHODS: We identified 60 of 924 kidney transplant recipients (KTRs) with isolated and untreated BLR. We analyzed the impact of predicted indirectly recognizable HLA epitopes (PIRCHE) score on future rejection, de novo DSA development, and recovery to baseline allograft function. Additionally, we compared the outcomes of different Banff rejection phenotypes. RESULTS: Total PIRCHE scores were significantly higher in KTRs with BLR compared to the entire study population (p=0.016). Among KTRs with BLR total PIRCHE scores were significantly higher in KTRs who developed TCMR/ABMR in follow-up biopsies (p=0.029). Notably, the most significant difference was found in PIRCHE scores for the HLA-A locus (p=0.010). PIRCHE scores were not associated with the development of de novo DSA or recovery to baseline allograft function among KTRs with BLR (p>0.05). However, KTRs under cyclosporine-based immunosuppression were more likely to develop de novo DSA (p=0.033) than those with tacrolimus, whereas KTRs undergoing retransplantation were less likely to recover to baseline allograft function (p=0.003). CONCLUSIONS: High PIRCHE scores put KTRs with BLR at an increased risk for future TCMR/ABMR and contribute to improved immunological risk stratification. The benefit of anti-rejection treatment, however, needs to be evaluated in future studies.

PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies.

Background: Indication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes. Methods: We analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm. Results: Group NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086). Conclusions: PIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies.