Differential Diagnosis of Kidney Graft Status

TGI has developed a novel peripheral blood test that can be used for routine serial monitoring to assist in managing patients with stable renal function without having to perform protocol biopsies. The TruGraf blood test enables differential diagnosis of Transplant eXcellence (TX) and not-TX through analysis of gene expression profiles. The reference population used to define TX includes patients with a serum creatinine level <2.3 mg/dL and stable renal function (<20% variability in current serum creatinine compared to the average of the past 3 measurements) together with a biopsy that shows no rejection and no other histological abnormalities. This profile is compatible with a state of immune quiescence.

TGI has also developed the first tissue-based molecular diagnostic test that defines all of the major biopsy states. Test services for research and diagnostic use are offered through TGI’s CLIA lab in Pleasanton, CA.

Peripheral Blood Test

The TruGraf blood test result will be reported as one of the following:

TX

The TruGraf blood molecular profile is TX. In validation studies comparing biomarker signatures in blood with histological phenotypes, samples with this profile have been correlated with a phenotype of Transplant eXcellence (TX). Transplant eXcellence (TX) is defined as a serum creatinine level <2.3 mg/dL and stable renal function (<20% variability in current serum creatinine compared to the average of the past 3 measurements) together with a biopsy that shows no rejection and no other histological abnormalities.

Not-TX

The TruGraf blood molecular profile is not-TX. In validation studies comparing biomarker signatures in blood with histological phenotypes, samples with this profile have not been correlated with a phenotype of Transplant eXcellence (TX). Transplant eXcellence (TX) is defined as a serum creatinine level <2.3 mg/dL and stable renal function (<20% variability in current serum creatinine compared to the average of the past 3 measurements) together with a biopsy that shows no rejection and no other histological abnormalities.

This minimally invasive blood test may be used for serial patient monitoring in place of, and with greater frequency than, protocol biopsies – and may be helpful in determining when a biopsy is called for even in the absence of a rise in serum creatinine. TGI’s TruGraf blood testing may also be helpful for monitoring and optimizing the effectiveness of immunosuppressive treatment between biopsies, and thus supports physician efforts to appropriately manage therapy, providing a degree of clinical utility absent in other blood tests. The primary focus will be on the TX patient group, i.e. those with stable renal function. The decision on how to proceed in an individual patient is entirely up to the attending physician taking into account her/his knowledge about the patient. In a patient with a TruGraf result of TX, the physician has the option of making no changes in therapy and continue to follow the patient with serial blood test monitoring, or to make a small decrease in the immunosuppression. In a patient with a TruGraf result of TX in sites that perform protocol biopsies, the physician has the option of performing the biopsy as scheduled, thereby correlating the validity of the test retrospectively, or to forsake the scheduled protocol biopsy and continue with serial monitoring. Similarly, in a patient with normal renal function and a molecular profile of not-TX, the physician has the option of making no changes in therapy and continue to follow the patient with serial blood test monitoring, or to make a small increase in the immunosuppression. Using the same analytical platform, unique molecular signatures for clinical acute rejection (cAR), subclinical acute rejection (SubAR), acute dysfunction with no rejection (ADNR) and chronic rejection (CR) have also been discovered. Future iterations of the TruGraf blood test will be directed towards detecting and differentiating between patients with these phenotypes.

Tissue Test

TGI has developed a test of kidney graft status based on global gene expression profiling of transplant biopsies. Our scientific founders have discovered molecular signatures based on 1,000 differentially expressed genes that define all the major biopsy states with high levels of sensitivity and specificity.

Gene expression profiling using the TGI test will provide transplant centers with an objective and informative molecular analysis of graft status that will complement conventional histological analysis and help resolve ambiguous or borderline cases. Such analysis is particularly well suited for smaller transplant centers with limited transplant pathology programs.