The time dependency of renal allograft histology

Abstract

Much of the complexity of the histological appearance of kidney transplant biopsies depends on the time at which the biopsies are obtained. It is well established that many elementary histological lesions and diagnoses have a time-dependent occurrence. While some "active" inflammatory lesions are noted primarily early after transplantation, other lesions are "chronic" and accumulate over time post-transplant, sometimes closely related to the prior active inflammatory lesions. With time after transplantation, the complexity of histology increases, by the co-occurrence of chronic damage and specific diseases. This leads to difficulties in clinical interpretation of the histological picture. We discuss the time-dependent prevalence of active and chronic lesions in kidney allograft biopsies and their associations with outcome. We also elaborate on the importance of time post-transplant in the interpretation of complex histological lesions or mixed diagnoses and illustrate that further research is necessary to evaluate whether time post-transplant is important for prognostication of graft injury processes. Adding a multidimensional prognostic layer to the current diagnostic Banff classification, including graft functional characteristics and time after transplantation, could become an interesting aid in the interpretation of complex histological lesions and mixed diagnoses, and in therapeutic decision-making.

Histological picture of antibody-mediated rejection without donor-specific anti-HLA antibodies: Clinical presentation and implications for outcome

“…It is well described that ABMR due to DSA is a waxing and waning process, which ultimately culminates in irreversible chronic lesions and graft failure. 18 Our multivariate models showed that the presence of HLA-DSA is more important for predicting outcome than reaching ABMR h , which corresponds to previous studies that showed an independent association of HLA-DSA and ABMR h with outcome. [19][20][21] This is not the case for HLA-DSA-negative patients with ABMR h , where our study suggests that this histology, in the absence of HLA-DSA, is often a transient phenomenon, without an increased risk of graft functional decline or graft failure.…”

“…18 Our multivariate models showed that the presence of HLA-DSA is more important for predicting outcome than reaching ABMR h , which corresponds to previous studies that showed an independent association of HLA-DSA and ABMR h with outcome. These patients had significantly fewer subsequent biopsies with ABMR h than HLA-DSA-positive patients, and less development of chronicity.…”

Banff survey on antibody-mediated rejection clinical practices in kidney transplantation: Diagnostic misinterpretation has potential therapeutic implications

“…To move in this direction, several key knowledge gaps need to be addressed. First a clear understanding of the natural histologic progression of ABMR in the setting of preformed and de novo DSA is critically needed to identify histologic, serologic, molecular, and/or clinical factors associated with inferior graft survival 12 . This will require a multicenter effort and close examination of both serial surveillance biopsies and clinically indicated biopsies in well-characterized patient cohorts who did and did not receive treatment.…”

Diagnosis of renal transplant rejection: Banff classification and beyond

“…Depending on the time post-transplantation and rejection activity, this condition can be classified as either acute/active or chronic. However, acute and chronic changes can exist within the same biopsy [19]. Importantly, although acute and chronic are clinical terms suggesting the time of onset of a disease, here, this classification reflects activity or inactivity, rather than time of biopsy.…”