The Significance of Subclinical Rejection and the Value of Protocol Biopsies

Abstract

Subclinical rejection (SCR) is diagnosed by protocol histology with a maximal prevalence occurring early after transplantation, falling to low levels by 1 year. Needle-core biopsy is safe, and the histology obtained fairly reflects subclinical immune activity. Several studies have consistently shown that SCR is associated with chronic tubulointerstitial damage, subsequent renal dysfunction and reduced graft survival. SCR is effectively treated by pulse corticosteroid therapy, although increased baseline immunosuppression may be necessary. A single randomized clinical trial of biopsy and corticosteroid therapy demonstrated significantly improved early structural and functional outcomes, and a (nonsignificant) 17% risk reduction in 4-year graft survival. Three possible approaches include: no protocol biopsies (usually accompanied by powerful immunosuppression); biopsies only in high-risk recipients (who may be difficult to reliably predict) or universal screening protocol biopsy (comprehensive but limited by cost and resource utilization). The appropriate screening methodology for a transplant unit is both a clinical and an economic decision; influenced by the SCR prevalence and potential gains of treatment, against costs and resource utilization. Further trials to quantify the cost-benefit balance in a typical, heterogeneous recipient population using modern immunosuppression are required.

Tacrolimus Exposure and Evolution of Renal Allograft Histology in the First Year After Transplantation

“…We indeed demonstrated that higher donor age and baseline histology is an independent risk factor for subclinical inflammation at 3 months, which is associated with higher increases in chronic graft damage later (19)(20)(21). It cannot be excluded that the subclinical infiltrates detected at 3 months are already present much earlier after transplantation, thus contributing to the early increase in chronic pathology, starting from implantation.…”

Scoring Total Inflammation Is Superior to the Current Banff Inflammation Score in Predicting Outcome and the Degree of Molecular Disturbance in Renal Allografts

“…ABMR was able to predict graft loss with 38% sensitivity and 96% specificity, whereas the total i-score is able to achieve moderate sensitivities (60-80%) with acceptable losses in specificity (60-80%). (16)(17)(18)(19)26,33 (16)(17)(18). Thus, the assessment and characterization of inflammation will remain an important task, both for histopathology and transcriptomics.…”

Cell-Free DNA: An Upcoming Biomarker in Transplantation

“…The importance of noninvasive graft monitoring is further emphasized as subclinical rejection may occur: these cases can exclusively be detected with (invasive) surveillance or protocol biopsies (13)(14)(15)(16)(17). Currently, to our knowledge, AlloMap is the only commercially available noninvasive organ transplant monitoring test (18).…”