Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications

The use of nonspecific immunosuppressive drugs has significantly reduced the incidence of acute kidney graft rejection (Sayegh & Carpenter, 2004). This led to a significant improvement in first-year graft survival rates that are “almost close to perfect”, as mentioned in a recent review (Lamb et al., 2011). However, the benefits of such immunosuppressive therapies on chronic rejection and overall long-term graft survival are uncertain (Meier-Kriescher et al., 2004a; McDonald et al., 2007). Thus, long term graft survival remains unchanged over decades (Meier-Kriescher et al., 2004a; Meier-Kriescher et al., 2004b). Persistent excessive immunosuppression −related to these immunosuppressive drugs− exposes renal transplant recipients to long-term toxicities including: increased incidence of cancers, severe infectious complications and “metabolic” diseases (for instance, diabetes, and accelerated atherosclerosis leading to cardiovascular diseases). An excess risk of cancer after renal transplantation has been increasingly recognized over recent decades (Penn et al., 1979; Kasiske et al., 2004; Grulich et al., 2007; Villeneuve et al., 2007; Webster et al., 2007; van Leeuwen et al., 2009), as advances in medicine have extended the life of renal transplant recipients. A meta-analysis including five studies of cancer risks in organ transplant recipients, including 31’977 organ transplant recipients −among which 97% have received a kidney graft− from Denmark, Finland, Sweden, Australia, and Canada shows an increase in the incidence of cancers related to infection with Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), hepatitis viruses B and C (HBV and HCV), and Helicobacter pylori with comparison to the general population (Grulich et al., 2007). However, cancer incidence after transplantation is not restricted to virus-induced cancers, since kidney cancer, myeloma, leukaemia, melanoma as well as bladder and thyroid cancers are more frequent in transplant recipients than the general population (Grulich et al., 2007). Common epithelial cancers (e.g., breast and prostate) occur at the same rate as the general population (Grulich et al., 2007). However, despite a cancer incidence similar with the general population, an interesting study reported a highly aggressive course of tumors and unresponsiveness to “classical” antitumoral chemotherapy in renal transplant recipients (Fiebiger et al., 2009). This report confirmed a pioneer work (Barrett et al., 1993) showing the more aggressive course of cancers in renal transplant recipients. Thus, malignancy is now one of the leading causes of patient’s