Chronic Allograft Nephropathy (Chronic Allograft Damage): Can It Be Avoided?

Abstract

Although there has been significant progress over the last three decades in renal transplantation, which has been driven primarily by improvements in short-term graft survival, there has been little parallel improvement in long-term outcomes. Advances in histological indicators of chronic allograft pathology have the potential to allow for earlier intervention as well as to provide surrogate endpoints for drug development. Identification of risk factors such as the presence of acute rejection episodes, ischemia/reperfusion injury, donor and recipient age considerations, hypertension, hyperlipidemia, glomerular hyperfiltration, and cytomegalovirus infection will aid in the development of strategies and treatments to mitigate these risks. Of particular importance is the optimization of immunosuppressive regimens to prevent acute rejection episodes. Despite our deeper understanding of clinical risk factors, it is clear that other determinants of graft loss have yet to be identified and that other "missing" factors must play a role in the pathogenesis of late kidney graft loss, highlighting the need for effective therapies to rescue declining graft function.

Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model

“…As a result, dialysis is required for these patients. Although the survival of grafts in living kidney transplantation has been greatly improved by the emergence of effective calcineurin inhibitors and antimetabolites ( 2 , 3 ), it is critical to secure organs from a wide range of donors to solve the problem of living donor shortage. Moreover, effective utilization of marginal organs from donors after cardiac death (DCD) is required.…”

“…The presence of acute rejection may trigger and lead to chronic allograft rejection. Thus, IRI increases the risk of developing a chronic allograft rejection over the long-term post-transplantation period, and outcomes have not improved despite appropriate immunosuppressant therapy after surgery ( 3 , 10 ). It is known not only in humans but also in animal models that ischemic kidney transplantation from DCD is less likely to survive long-term and undergo chronic rejection than transplantation from living donors ( 11 , 12 ).…”

Composition and diversity analysis of the B‑cell receptor immunoglobulin heavy chain complementarity‑determining region 3 repertoire in patients with acute rejection after kidney transplantation using high‑throughput sequencing

“…Scholars then began to explore kidney transplantation and experiments revealed that successful kidney transplantation may significantly improve the quality of life for patients with ESRD. Advances in immunosuppression over the last three decades have led to vast improvements in the control of acute rejection and short-term graft survival in kidney transplant patients (4). However, no significant improvements in long-term outcomes have been achieved, and concerns over the morbidity of lifelong regimens of immunosuppressive drugs remain.…”