Impact of Subclinical Borderline Inflammation on Kidney Transplant Outcomes

Abstract

Background. Surveillance biopsies permit early detection of subclinical inflammation before clinical dysfunction, but the impact of detecting early subclinical phenotypes remains unclear. Methods. We conducted a single-center retrospective cohort study of 441 consecutive kidney transplant recipients between 2015 and 2018 with surveillance biopsies at 6 months post-transplant. We tested the hypothesis that early subclinical inflammation (subclinical borderline changes, T cell-mediated rejection, or microvascular injury) is associated with increased incidence of a composite endpoint including acute rejection and allograft failure. Results. Using contemporaneous Banff criteria, we detected subclinical inflammation in 31%, with the majority (75%) having a subclinical borderline phenotype (at least minimal inflammation with mild tubulitis [>i0t1]). Overall, subclinical inflammation was independently associated with the composite endpoint (adjusted hazard ratio, 2.88; 1.11-7.51; P = 0.03). The subgroup with subclinical borderline inflammation, predominantly those meeting the Banff 2019 i1t1 threshold, was independently associated with 5-fold increased hazard for the composite endpoint (P = 0.02). Those with concurrent subclinical inflammation and subclinical chronic allograft injury had worse outcomes. The effect of treating subclinical inflammation was difficult to ascertain in small heterogeneous subgroups. Conclusions. Subclinical acute and chronic inflammation are common at 6 months post-transplant in kidney recipients with stable allograft function. The subclinical borderline phenotype with both tubulitis and interstitial inflammation was independently associated with poor long-term outcomes. Further studies are needed to elucidate the role of surveillance biopsies for management of allograft inflammation in kidney transplantation.

Abnormal time‐zero histology is predictive of kidney transplant outcomes

“…Molecular pathology studies have found overlap between gene expression patterns in indication biopsies with acute rejection and injury and biopsies with chronic allograft injury. [35][36][37][38] Given the mixed reports of the benefits of treating subclinical acute rejection, 29,[39][40][41] the potential relationship between time-zero histology and subsequent subclinical rejection needs further evaluation in future studies.…”

“…[26][27][28] Surveillance biopsies were performed at 6 months post-transplant, as reported previously. 29 Indication biopsies were performed to investigate allograft dysfunction at the discretion of the treating physician.…”

Flat Pattern Peaks of Tacrolimus Absorption and Associated Pharmacogenomic Variants in Kidney Transplantation Recipients

“… 16 Borderline change is also reported to be independently associated with poor long term graft outcomes. 17 18 Thus, flat pattern peak causes the increased risk of BPAR and/or borderline change and can be associated with poor long term graft outcomes.…”

Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injury

“…In addition, higher normalized evDNA yield, evDNA copy number, and dd-evDNA copy number correlated with inflammation in the kidney allograft (specific Banff scores > 0). Previous studies have shown that subclinical inflammation is a relatively common finding in surveillance allograft biopsies, identifying a high-risk group of kidney recipients for poor subsequent outcomes (Seifert et al, 2021). Other studies focusing on kidney injury observed larger uEV size in properly controlled diabetic patients compared with healthy controls (Freeman et al, 2018), whereas no changes in uEV size were observed when comparing different groups of patients with acute or chronic glomerular disease (Dimuccio et al, 2020).…”