The perils of immunosuppression minimization: lessons from protocol biopsies of renal allografts

To emphasize the pathogenicity of subclinical cellular inflammation in renal transplant recipients, and its relation to poor graft outcomes and the development of de-novo donor-specific antibody (DSA).

Protocol biopsies have identified the gene signatures of innate and adaptive immunity in patients with minimal inflammation that correlate with the subsequent development of graft interstitial fibrosis, transplant glomerulopathy and antibody-mediated rejection. The risks of immunosuppression minimization, especially in HLA mismatched donor-recipient pairs, are highlighted.

The major cause of renal allograft loss is immunological and a contributor to this is the minimization of immunosuppression. The prevention of premature graft loss requires better matching of class II HLA antigens, the targets of de-novo DSA, and monitoring for subclinical inflammation rejection with protocol biopsies or urine chemokines.