Subclinical inflammation and renal allograft dysfunction: myth or reality?

Abstract

Since the implementation of the Banff classification, the diagnosis and treatment of transplant rejection has been standardized. However, the rigid categorization of transplant pathology has limited our perspective on allograft inflammation, particularly disregarding those inflammatory infiltrates who do not reach the category of rejection. The term subclinical inflammation was introduced to designate the inflammation found in protocol biopsies, without significant renal function deterioration. Following the introduction of modern immunosuppression with tacrolimus and mycophenolate, subclinical rejection rate decreased, and less attention was paid to this entity. However, in the last decades several studies have evaluated the impact of lower levels of inflammation and demonstrated its negative consequences on long-term outcomes. Although, in some patients this subclinical inflammation is not permanent and can spontaneously disappear. The uncomplete definition of subclinical inflammation, which only considered renal function stability, and the evaluation of the biopsy as a definitive diagnosis, and not as a picture of an evolving process are the main reasons why managing this inflammation represents a challenge, especially when there is no pathogenic mechanism identified. In this review, we revise the "natural" history of inflammation in the kidney allograft and its possible origins based on cellular composition and transcriptomic expression changes in kidney biopsies. In addition, we propose an updated definition and an approach to manage it.