The mechanisms of chronic kidney damage in renal transplant and their possible reversibility

Chronic allograft dysfunction (CAD) represents the main cause of delayed graft loss. Several mechanisms, immunological and not, are involved in the pathogenesis of CAD, some of which are modifiable. Suboptimal immunosuppression may induce subclinical acute rejections, identifiable by histology and influencing graft survival. Typical transplant recipients' comorbidities such as hypertension, diabetes and dyslipidemia accelerate CAD progression. Calcineurin inhibitors, which are known to be nephrotoxic, play a key role in the onset of CAD through several mechanisms. Therapeutic interventions to stop or at least slow down CAD progression involve all these modifiable factors by means of comorbidity correction, tailored immunosuppression and, in some cases, withdrawal of calcineurin inhibitors.