Chronic Allograft Dysfunction

GENERAL PRINCIPLES

• Chronic allograft dysfunction accounts for the vast majority of late graft losses and is the major obstacle to long-term graft survival.

• Chronic allograft dysfunction (formerly chronic rejection) is a slowly progressive, insidious decline in function of the allograft characterized by gradual vascular and ductal obliteration, parenchymal atrophy, and interstitial fibrosis.

DIAGNOSIS

• Diagnosis is challenging and generally requires a biopsy. The rejection process is mediated by immune and nonimmune factors.

• The manifestations of chronic rejection are unique to each organ system.

TREATMENT

To date, no effective therapy is available for established immune-mediated chronic allograft dysfunction. Some patients, particularly those with renal transplants, will require a second solid organ transplant. Current investigational strategies are aimed at prevention.

Biomarkers

• The incidence of acute rejection varies between allograft types. Current recommended routine markers/imaging (i.e., serum creatinine in kidney transplant and echocardiogram in heart transplant) are not sensitive enough to detect graft damage in the early stages of rejection. There are limitations of invasive biopsy for routine surveillance. Noninvasive biomarkers could serve as predictive factors for rejection for early identification of allograft injury and prompt early intervention.

• Unbiased high-throughput gene expression profiling technologies and donor-derived cell-free DNA testing are other tools that can help provide further information into the health of an allograft. These technologies are available in kidney and heart transplant, but not currently available for other organ transplants.⁴