559suffer heart disease, diabetes, infections and cancer. These drugs are also toxic, and
they can slowly poison the very kidney they are protecting. They can also cause
hypertension and hyperlipidemia, eventually leading to the failure of the new kid-
ney transplant – a condition known as chronic allograft nephropathy.
Unlike acute rejection, which is entirely the result of the immune system attack-
ing the transplanted organ, chronic allograft nephropathy may be a result of the
immune system, the immunosuppressive drugs, or both. It is a major problem in
kidney transplantation and >50 % of biopsies taken from kidney transplant patients
who appeared to be doing well only 2 years after transplantation already show signs
of chronic allograft nephropathy. Serum creatinine, the currently used biomarker to
monitor renal transplant patients, is an insensitive, late-trailing indicator of graft
function. When creatinine levels are elevated, biopsies are generally performed to
assess whether graft function has been compromised and, if so, identify the cause
through histological analysis. Biopsies are costly, disruptive, subjective and inva-
sive. They carry the risk of complications and, in one third of the cases, fail to yield
useful, actionable information. Gene expression profi ling could be used to defi ne a
unique molecular signature for chronic allograft nephropathy. Use of this knowl-
edge could help to personalize kidney transplantation and reduce the morbidity.
Transplant Genomics Inc is developing tests that use a broad range of genomic
and proteomic tools capable of revealing the complexity of the underlying biology,
which is well known to be highly heterogeneous. Compared to conventional
methods, these tests will enable earlier detection of graft dysfunction and differen-
tial diagnosis among actionable causes, providing an opportunity for physicians to
take clinical actions to prolong graft and patient survival. These tests can be used,
e.g., in monitoring patients to detect subclinical rejection, deciding when to perform
biopsies rather than relying on protocols or waiting for creatinine levels to rise; for
optimizing minimization of immunosuppression therapy by ensuring early detec-
tion of an immune response; and in molecular profi ling of biopsies to complement
conventional histology and help resolve ambiguous or borderline cases.
Personalization of Cardiac Transplantation
AlloMap MolecularTesting (CareDx Inc) is a non‐invasive gene expression test
used to aid in the identifi cation of heart transplant recipients who have a low prob-
ability of moderate/severe acute cellular rejection at the time of testing in conjunc-
tion with standard clinical assessment. AlloMap testing measures the expression
levels of 20 genes from a blood sample. The combined expression of these genes is
represented as an AlloMap test score. AlloMap, cleared by the FDA and CE-marked
in EU, is performed in the CareDx CLIA‐certifi ed laboratory. Use of AlloMap is
also included in the International Society for Heart and Lung Transplantation
Practice Guidelines, the worldwide standard for the care of heart transplant patients.
AlloMap assays the RNA levels of 11 rejection biomarker genes and 9 control
genes, for identifi cation of heart transplant recipients who have a low probability of
Personalized Approaches to Improve Organ Transplantation