For the thousands of people receiving life-saving kidney transplants every year, the risk of organ rejection is a constant concern. Rejection, especially “silent” subclinical acute rejection, can be difficult to detect early without proper monitoring. Traditional methods of monitoring can be limited and often require invasive biopsies. TruGraf Kidney is the only non-invasive biomarker test validated for surveillance of stable kidney transplant recipients. With TruGraf Kidney, clinicians are revolutionizing the way they monitor patients’ graft health with precision and accuracy.

Serial Surveillance of Kidney Transplant Recipients with TruGraf® Kidney

TruGraf Kidney is the first non-invasive blood test that offers clinicians the earliest opportunity to rule out “silent” subclinical acute rejection (subAR), prior to signals of kidney damage such as a rise in serum creatinine or donor-derived cell-free DNA, without having to perform a risky and invasive tissue biopsy.

Centers currently performing only clinical monitoring and “for cause” biopsies are missing all cases of subAR, leading to worse outcomes for the 25% of patients that have subAR. Serial surveillance may improve outcomes by reducing the risk of developing cAR, reducing the formation of de novo DSA, reducing graft loss at five years, reducing graft fibrosis (IFTA 2+) and reducing loss of GFR.

Key benefits of serial surveillance with TruGraf include:

Patients avoid painful, risky, invasive procedures that are negative 75% of the time.
Patients and their caregivers know that they don’t harbor “silent” subclinical rejection.
Healthcare professionals can stratify patients into those who may benefit from surveillance biopsy and those who likely won’t, allowing them to eliminate unnecessary biopsies and focus interventions on patients experiencing rejection.

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TruGraf Kidney:

the Earliest Possible Blood Test to Rule Out “Silent” Rejection

TruGraf measures differentially-expressed genes in the blood of kidney transplant recipients with stable renal function to identify those patients who are adequately immunosuppressed, and by doing so rule out subAR.

SubAR is termed “silent” because it cannot be detected by current non-invasive standard of care tests, and can only be detected by invasive surveillance tissue biopsies. 25% of stable kidney transplant recipients are experiencing “silent” rejection — potentially leading to organ failure before observable symptoms of rejection appear — culminating in worse long-term outcomes.

Five Consequences of Untreated subAR*

1. Higher risk of developing clinical acute rejection (cAR)

2. More likely to form de novo donor-specific antibodies (DSA)

3. More likely to lose the graft at 5 years

4. More likely to develop graft fibrosis (IFTA 2+)

5. More rapid loss of glomerular filtration rate (GFR)

*Friedewald JJ, Kurian SM, Heilman RL, Whisenant TC, Poggio ED, Marsh C, Baliga P, Odim J, Brown MM, Ikle DN, Armstrong BD, Charette JI, Brietigam SS, Sustento-Reodica N, Zhao L, Kandpal M, Salomon DR, Abecassis MM; Clinical Trials in Organ Transplantation 08 (CTOT-08). Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant. Am J Transplant. 2019 Jan;19(1):98-109. doi: 10.1111/ajt.15011. Epub 2018 Aug 31. PMID: 29985559; PMCID: PMC6387870.

Interpretation of Results for TruGraf Kidney

TruGraf utilizes microfluidic PCR technology to measure differentially-expressed genes in the blood of kidney transplant recipients with stable renal function as a diagnostic tool to rule out subclinical rejection, confirming immune quiescence.

TruGraf compares a patient’s blood gene expression profile to a reference population created from a patient population with biopsy confirmed status.

Patients receive a simple binary result:

Transplant eXcellence (TX), negative for subclinical rejection (NPV: 91%)
Not-TX, positive for subclinical rejection (PPV: 65%)

TruGraf Kidney is Clinically Validated for Surveillance and Published in Peer-Reviewed Journals

Source:

Key Takeaways:

R.L. Heilman, J.N. Fleming, M. Mai, B. Smith, W.D. Park, J. Holman, M.D. Stegall. Multiple Abnormal Peripheral Blood Gene Expression Assay Results are Correlated with Subsequent Graft Loss After Kidney Transplantation. Clinical Transplantation, April 2023

TruGraf shows long term worse graft survival when persistently positive:

Correlated peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation.
Conducted a prospective, multicenter observational study of peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay.
Enrolled 240 kidney transplant recipients
Concluded that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

S. Park; K. Guo; R. Heilman, L. Raymond; E. Poggio; D. Taber; C. Marsh; S. Kurian; S. Kleiboeker; J. Weems; J. Holman; L. Zhao; R. Sinha; S. Brietigam; C. Rebello; M. Abecassis; J. Friedewald. Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients. Clinical Journal of the American Society of Transplant, October 2021

First paper published that demonstrates GEP and dd-cfDNA are complementary in surveillance:

428 biopsy-paired samples at 2-6, 12, and 24 months post-transplant in 208 clinically stable patients with ≥1 biopsy-paired sample
Incidence of biopsy-proven subclinical rejection was 24%.
Two blood-based biomarker assays (GEP and dd-cfDNA) collected at the time of biopsies.
Demonstrated increased efficacy for both GEP and dd-cfDNA when utilized together in combination for assessment of patient health

A. Ang, C. Schieve, S. Rose, C. Kew, M. R. First, and R. B. Mannon. Avoiding Surveillance Biopsy: Use of a Noninvasive Biomarker Assay in a Real-Life Scenario. Clinical Transplantation, November 2020

Clinicians recognize TruGraf’s utility in supporting their clinical decision making:

This prospective single-center study correlated TruGraf with a 6-month biopsy (SBx) and included 90 kidney transplant patients
77% of clinicians thought the test offered clinical utility
71% of clinicians thought the test supported the decision to avoid surveillance biopsies in this population

V. R. Peddi, P. S. Patel, C. Schieve, S. Rose, and M. R. First. Serial Peripheral Blood Gene Expression Profiling to Assess Immune Quiescence in Kidney Transplant Recipients with Stable Renal Function. Annals of Transplantation, April 2020

TruGraf has clinical utility for centers not utilizing surveillance biopsy as part of their protocol:

Single-center prospective, non-interventional clinical study for kidney transplant recipients not monitored by surveillance biopsy
28 subjects tested with with 2 or 3 serial tests (14 per cohort)
A ‘rule out’ test may enable a reduction of a large proportion of protocol biopsies. For those centers that do not utilize these, far fewer patients could be subjected to the risks of biopsy
Non-invasive blood testing can be done more frequently than surveillance kidney biopsies, is significantly less invasive, less painful, and less risky for patients,

C. L. Marsh, S. M. Kurian, J. C. Rice, T. C. Whisenant, J. David, S. Rose, C. Schieve, D. Lee, J. Case, B. Barrick, V. R. Peddi, R. B. Mannon, R. Knight, D. Maluf, D. Mandelbrot, A. Patel, J. J. Friedewald, M. M. Abecassis, and M. R. First. Application of TruGraf v1: A Novel Molecular Biomarker for Managing Kidney Transplant Recipients With Stable Renal Function. Transplantation Proceedings, April 2019.

TruGraf’s high negative predictive value (NPV) provides an invaluable tool for monitoring patients’ noninvasively:

Data gathered from 7 transplant centers across the country showed that TruGraf concordance between product result and clinical and/or histologic examination was 74%
A result of TX (negative for subclinical acute rejection) was accurate for 93% of cases
The observed negative predictive value for TruGraf was 90%, with a sensitivity of 74% and specificity of 73%.

M. R. First, V. R. Peddi, R. Mannon, R. Knight, C. L. Marsh, S. M. Kurian, J. C. Rice, D. Maluf, D. Mandelbrot, A. Patel, J. David, C. Schieve, D. Lee, P. Lewis, J. J. Friedewald, M. M. Abecassis, and S. Rose. Investigator Assessment of the Utility of the TruGraf Molecular Diagnostic Test in Clinical Practice. Transplantation Proceedings, December 2018

7 transplant centers: TruGraf is an invaluable addition to the transplant physician’s tool kit:

87.5% indicated that TruGraf results influenced their decision regarding patient management.
87% indicated that TruGraf results supported physicians’ decisions on patient management.
93% indicated that they would use serial TruGraf testing in future patient management.

M. R. First, T. C. Whisenant, J. J. Friedewald, S. Rose, D. Lee, S. M. Kurian, D. Pierry, P. Lewis, T. Gelbart, and M. M. Abecassis. Clinical Utility of Peripheral Blood Gene Expression Profiling in Kidney Transplant Recipients to Assess the Need for Surveillance Biopsies in Subjects with Stable Renal Function. Journal of Transplantation Technologies & Research, November 2017, 7:3

TruGraf has unmatched performance compared to current surveillance standards.

The TruGraf TX (Transplant eXcellence) result proved to have a high degree of accuracy in correlating with 88% of biopsy results.
If Transplant Centers utilized TruGraf in place of surveillance biopsies, 107/125 (86%) of patients with stable renal function would have avoided an invasive biopsy.

M. R. First, D. Pierry, M. McNulty, S. M. Kurian, S. Rose, T. C. Whisenant, T. Gelbart, A. Venzon, N. Bayat, P. Lewis, J. J. Friedewald, M. M. Abecassis, and D. Lee. Analytical and Clinical Validation of a Molecular Diagnostic Signature in Kidney Transplant Recipients. Journal of Transplantation Technologies & Research, September 2017, 7:3

TruGraf was designed with the unique intent of monitoring stable kidney transplant recipients.

TruGraf was built on a foundation of 793 paired blood and biopsy samples.
Discovery set 498; external validation 295 paired blood/biopsy samples.
Successfully confirmed analytical sensitivity, specificity, reproducibility, and quality control.

Transform Kidney Transplant Monitoring with TruGraf

TruGraf Kindey is intended for use in patients with stable renal function to assess immune status as an alternative to surveillance biopsy in kidney transplant patients who are more than 90 days post transplant

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Subclinical Acute Rejection