Immunosuppressive drug therapy and subclinical acute renal allograft rejection: impact and effect

The incidence of subclinical acute rejection (SCAR) varies between 5% and 15% with current maintenance immunosuppressive drug regimens. Despite many similarities between SCAR and clinical acute rejection exist, the inflammatory activated cell infiltrates are not completely identical while graft cytokine profiles and counteractive immune responses are characterized by subtle differences that could explain why SCAR is not accompanied by immediate graft dysfunction. Evidence that SCAR contributes to chronic allograft damage (interstitial fibrosis and tubular atrophy) and negatively affects graft outcome is counterbalanced by the scarcity of controlled data proving the beneficial effect of SCAR treatment. The development of sensitive and specific noninvasive methods to monitor the immune status of the graft by using mRNA determinations, gene expression analysis (microarrays), proteomic analysis, and magnetic resonance spectroscopy, can help to ultimately replace protocol biopsies and also contribute to the further unraveling of the complex underlying immunological mechanisms responsible for SCAR. The latter would enable clinicians to preemptively make strategic adjustments to immunosuppressive therapy in an attempt to further improve renal allograft survival and clinical care of the transplant patient.