Kidney transplantation is the primary therapy for end-stage renal disease (ESRD; stage 5 chronic kidney disease). US data for 2013 show that the most common primary causes of ESRD in renal transplant recipients were diabetes (30.1%), hypertension (21.2%) and glomerulonephritis (21.1%) (US Renal Data System [USRDS], 2015).
While transplantation is limited by the supply of organs (Abecassis et al., 2008; Sayegh, 2009; Broumand, 2015), there have been marked improvements in acute rejection rates and graft survival in the year after transplantation. One year after kidney transplantation, over 90% of deceased-donor grafts and 97% of living donor grafts remain functioning (Gondos et al., 2013; US Department of Health and Human Services, 2014; USRDS, 2015). Unfortunately, these advances have not translated into similar long-term graft survival with up to 25% of patients returning to dialysis by 5 years (Gondos et al., 2013; Morales et al., 2012; US Department of Health and Human Services, 2014) and 50% of grafts failing by 10 years (Gondos et al., 2013; US Department of Health and Human Services, 2014).
Chronic antibody-mediated rejection has been implicated as a common cause of late graft failure. However, a recent study also identified arterial hyalinosis and glomerulosclerosis as causes of graft damage (Stegall et al., 2018); both are injuries associated with calcineurin inhibitor (CNI) exposure and antibody-mediated rejection (Einecke et al., 2017). Ongoing studies are exploring new immunosuppressive regimens to assess whether a reduction in CNI exposure can be achieved with comparable efficacy outcomes (Pascual et al., 2018).