Noninvasive methods to assess the risk of kidney transplant rejection

Abstract

In current clinical practice, immune reactivity of kidney transplant recipients is estimated by monitoring the levels of immunosuppressive drugs, and by functional and/or histological evaluation of the allograft. The availability of assays that could directly quantify the extent of the recipient's immune response towards the allograft would help clinicians to customize the prescription of immunosuppressive drugs to individual patients. Importantly, these assays might provide a more indepth understanding of the complex mechanisms of acute rejection, chronic injury, and tolerance in organ transplantation, allowing the design of new and potentially more effective strategies for the minimization of immunosuppression, or even for the induction of immunological tolerance. The purpose of this review is to summarize results from recent studies in this field. Keywordsbiomarker; CD30; Cylex ™ ; ELISPOT; immune monitoring; proteomic; transplantation Transplant recipients, by and large, require immunosuppression indefinitely for the lifespan of their graft to prevent rejection; long-term maintenance of immunosuppression becomes a balance between suppressing rejection against the allograft and the toxicities associated with therapy, such as infections and malignancy. Acute clinical rejection still represents one of the major risk factors for poor long-term graft outcome [1] and, in kidney transplantation, the diagnosis of acute rejection is confirmed by renal allograft biopsy, which carries a finite risk of complications [2]. In clinical practice, a biopsy is commonly undertaken if there is a rise in serum creatinine of at least 15% above baseline, although this approach may fail to detect injury at its inception [3]. Indeed, serum creatinine is a relatively insensitive marker of renal dysfunction, which increases only in the late phases of injury when there has already been substantial functional loss. Moreover, in the absence of any changes in serum creatinine, up to one-third of renal allografts will demonstrate histological signs of acute rejection in the first 3 months after transplant [4]. These so-called 'subclinical rejections', if not detected and properly treated, may negatively affect long-term graft outcomes [5]. Protocol allograft biopsies may †Author

Immune cell function assay does not identify biopsy‐proven pediatric renal allograft rejection or infection

“…Ideally, a non‐invasive biomarker that accurately predicts graft rejection would be most suitable for long‐term management of immunosuppression in pediatric renal transplant patients . Serum creatinine and peripheral blood measurements of chronic immunosuppressive drug levels have been used for therapeutic supervision of patients post‐transplantation.…”

Immune monitoring and biomarkers to predict chronic allograft dysfunction

“…17,18 A major issue in the literature is that many of the studies are single center or consist of small numbers of patients from multiples centers and have yet to be validated in large patient populations. The recently conducted Clinical Trials in Organ Transplantation is a series of consortium studies in immune monitoring sponsored by the National Institute of Allergy and Infectious Diseases.…”

Novel diagnostics in renal transplantation

“…High throughput microarray technology offers a means to study disease-specific transcriptional changes in tissue biopsy, peripheral blood and biofluids. 6,[8][9][10][11][12][13] Much of the available data on gene expression profiling has been obtained using renal biopsy tissue. The key studies have defined a molecular signature of acute rejection, 8 discovered a novel biomarker for chronic antibody mediated rejection, 14 and identified a "superior" molecular score to predict acute rejection in renal biopsy samples.…”