Dr. Beje Thomas is board certified in internal medicine and nephrology. He completed a general nephrology fellowship at the University of Connecticut Health Center. He went on to complete an additional year of training in transplant nephrology at the Medical University of South Carolina. Dr. Thomas previously served as a professor of medicine with the Medical University of South Carolina, the University of Maryland Medical Center and Georgetown University School of Medicine.

Dr. Thomas has been actively involved in research and medical education throughout his career. Currently, he is the medical director of the Adult Kidney and Pancreas Program at Froedtert Memorial Lutheran Hospital and an Associate Professor of Medicine at the Medical College of Wisconsin. One of Dr. Thomas’s focuses is overcoming barriers to increase awareness and access to transplantation.

Dr. Thomas recently spoke on a Eurofins Transplant Genomics webinar about the role of belatacept in transplant care and the use of biomarkers like TruGraf and TRAC-ID in real-world monitoring during conversion. The discussion from the webinar, which was grounded in clinical experience and supplemented by case-based learning, is captured in the article below.

Why Belatacept? Rethinking CNI-Centered Regimens

For decades, the story of immunosuppression has been woven into the tale of transplant medicine. For early kidney transplants, 1-year acute rejection rates were as high as 90%. As more and better immunosuppressive medications were available, those rates dropped precipitously. When tacrolimus and similar medications became available in the 1990s, rejection rates continued to plummet. Today, thanks in part to CNI-centered regimens like tacrolimus, first-year rejection rates are as low as 5% to 8% for kidney transplants.

The most common immunosuppression regimen used today is a combination of tacrolimus with MMF and/or steroids. Close to 80% of treatments use these methods. According to Dr. Thomas, as of mid-2025, only around 3% of centers use belatacept de novo. However, belatacept use is growing, especially in conversion cases.

Reducing CNI-Associated Risks

One driving factor for increased belatacept use is CNI-associated toxicity. CNI medications can induce side effects or complications, including nephrotoxicity, neurotoxicity, hypertension, diabetes, or thrombotic microangiopathy. They may also increase risks for patients who already have some of these conditions.

Some biopsies have found interstitial fibrosis and tubular atrophy that may be related to CNI toxicity. Dr. Thomas notes that in the first 6 years, acute rejection is responsible for close to half of kidney graft failures. Other causes of kidney graft failure in the first 6 years include:

Transplant glomerulopathy (9%)
Interstitial fibrosis and tubular atrophy (11%)
Recurrence of the primary disease (4%)
BK nephropathy (7%)

After 6 years, acute rejection is responsible for only around a quarter of kidney graft failures. Other major causes of long-term graft failure include:

Transplant glomerulopathy (32%)
Interstitial fibrosis and tubular atrophy (16%)
Recurrence of the primary disease (13%)
BK nephropathy (2%)

Dr. Thomas notes that transplant glomerulopathy and interstitial fibrosis and tubular atrophy can sometimes be traced, in part, to CNI use. “The quest for us,” he says, “Is to maximize immunosuppression to prevent rejection but minimize it to avoid any kinds of side effects and hopefully help the kidney transplant last longer.”

Supporting Higher-Risk Kidneys

Not every transplanted kidney is the same quality. According to data published by the Organ Procurement & Transplantation Network, the half-life for a living donor kidney is 12.48 years. Kidneys from deceased donors have expected half-lives between 5.60 and 11.44 years on average, depending on their Kidney Donor Profile Index (KDPI).

KDPI of 0-20%: Half life of 11.44 years
KDPI of 21-85%: Half life of 8.90 years
KDPI of 86-100%: Half life of 5.60 years

The hope of clinical teams, says Dr. Thomas, is to “try to allow these kidneys to actually last longer — as long as possible.” In some cases, belatacept may help teams better protect the renal function that exists in marginal kidneys early in the post-transplant timeline.

Cases of Prolonged Delayed Graft Function or Slow Graft Function

A patient may get a transplant and go on a tacrolimus-based immunosuppression regimen. However, they have prolonged delayed graft function. Delayed graft function refers to any situation where a kidney transplant patient requires dialysis within the first 7 days post-transplant.

Dr. Thomas says sometimes the transplanted kidney “has to wake up and start functioning so the patient doesn’t need dialysis.” However, if this situation is prolonged, Dr. Thomas notes there are clinicians promoting the removal of CNI-based regimens to improve vascular flow and decrease potential injury to the kidney. In such cases, the patient might be converted to belatacept for this purpose, as belatacept doesn’t cause vasoconstriction.

Dr. Thomas also notes that clinical teams might turn to belatacept in cases of slow graft function, where the kidney function is not as optimal as the team thinks it should be.

Risks to Manage: What Belatacept Demands of Clinicians

Belatacept is non-nephrotoxic and non-diabetogenic. It also offers perceived benefits for conversion and early protection of renal function. Dr. Thomas presented a case posted in the Clinical Journal of the American Society of Nephrology that demonstrated that conversion to belatacept post-transplant was associated with a lower risk of graft failure (78% graft survival versus 63% in the CNI control group 7 years post conversion) and acceptable safety outcomes.

However, belatacept is not without its own risks, and Dr. Thomas says, “Not every patient can have belatacept.”

Risks to manage during belatacept conversion include:

An increased risk of T-cell mediated rejection compared to CNI-based regimens
An association with post-transplant lymphoproliferative disease (PTLD)
An increased risk of infection, particularly with CMV (a sevenfold increase in risk)

Dr. Thomas notes that patients without immunity to EVB (seronegative patients) are at particular risk of developing PTLD. Because of this, belatacept use, conversion or otherwise, is contraindicated for patients with EBV seronegative or unknown status.

A Growing Role for Belatacept in Clinical Practice

Belatacept use is growing in immunosuppression. From June 2011 to December 2018, de novo use of belatacept-based therapy increased from 0.74% to 3.11%. Impediments to wider adoption include the risks mentioned above as well as the need for monthly IV infusion (compared to tacrolimus, which is administered in pill form).

However, the benefits of belatacept conversion in cases where patients don’t do well on CNI-based regimens or to protect graft function early and support ongoing graft health longer can’t be ignored. Even one of the adoption obstacles — IV delivery monthly — can be a benefit in cases where medication compliance is low. To more confidently adopt belatacept when it may be a better choice for patients, clinical teams need a noninvasive way to proactively monitor subclinical immune activation or injury before symptoms appear.

Dr. Thomas goes on to discuss how molecular biomarkers like TruGraf and TRAC-ID provide that necessary level of insight.

Why Molecular Diagnostics? The Role of TruGraf and TRAC-ID

TruGraf is a gene expression profile that Dr. Thomas says is good at picking up subclinical rejection even before there’s damage that shows up via other clinical tests. TRAC is a cell-free donor DNA assay that helps classify actual damage to the kidney. The “ID” portion of TRAC-ID stands for infection disease; it looks at the TTV viral load as a sort of thermometer that helps clinical teams gauge whether immunosuppression is too high, too low, or well-balanced.

Gene expression profiling and dd-cfDNA serve complementary purposes in post-transplant treatment, and the TTV data provided by TRAC-ID offers a third dimension of insight that helps teams estimate the net state of immunosuppression. This level of insight helps teams move away from the traditional reactive monitoring afforded by creatinine and other tests and move toward proactive but noninvasive surveillance of graft health.

Case Study: Post-Conversion Surveillance in Action

Dr. Thomas presented a real-world case study that applied the biomarkers to monitoring a belatacept initiation. A 70-year-old male had received a deceased donor transplant earlier in the year. The KDPI was less than 85%, and there was immediate post-transplant graft function. At the time of discharge, serum creatinine (SCr) was around 1.5 mg/dL.

Initially, the immunosuppression regimen was tacrolimus with a goal of 8-10 ng/mL, Mycophenolate Mofetil 1 g twice daily, and prednisone 5 mg daily. Dr. Thomas says, overall, the patient was doing well. However, over the course of the first 2 to 3 months, the SCr trended up a little each time they checked it.

The team’s next step was to evaluate the patient, including going through a normal history and physical. They did a kidney ultrasound with Doppler looking for any obvious obstruction and considered whether there were any pre-transplant issues. They also looked at the potential for non-adherence to the drug regimen. All of these came back normal or not an issue, and proteinuria was about 0.5 g/day.

The team also ran TruGraf, which showed TX, indicating negative for subclinical rejection. “So, the chance of rejection was on the lower side,” says Dr. Thomas. “But not everything is about rejection. There’s also other things that can happen, such as CNI toxicity.”

Wondering if this might be the case, the team moved forward with a biopsy. It showed isometric vacuolization, indicating possible CNI-based toxicity. At that point, the patient was converted to belatacept. This involved the infusion of 5 doses for the loading dose and monthly doses afterward. They continued the 5 mg prednisone daily. Tacrolimus was weaned over 2-3 months, and TruGraf was checked monthly.

Two months after conversion, with the tacrolimus goal set at 2-4 ng/mL, TruGraf came back not-TX. In response, the tacrolimus goal was increased to 4-6 ng/mL. Around the same time, SCr was elevated at 4.2 mg/dL. Between the rising SCr and the not-TX result, the team was very concerned about rejection. At this point, a biopsy found ACR 2a, leading the team to treat the patient aggressively with thymoglobulin and increased tacrolimus. Dr. Thomas notes that cf-ddDNA was also elevated at the time of the rejection.

Ultimately, the patient was put on quadruple therapy with belatacept, tacrolimus, mycophenolic acid, and prednisone. His SCr was 1.5 mg/dL post-treatment, and his TRAC-ID was 0.34% with TTV detected and in range for optimum immunosuppression. Dr. Thomas says TRAC-ID will be repeated monthly to help the team understand and respond to trends in the patient’s immunosuppression.

Interpreting Biomarker Discordance: A Clinical Framework

“It’s important to know the type of patients you work with,” says Dr. Thomas. “In our practice, if someone is going to be converted to belatacept, we would do a baseline TruGraf and then do TruGraf monthly while we’re converting them over. After belatacept is loaded and we’re lowering the tacrolimus or weaning it off, again, monthly TruGraf tests to see where they’re at. If there’s ever a non-TX, then we would check TRAC-ID if time permits — especially if SCr is relatively stable — to see what’s going on and where we are at. If the TRAC-ID isn’t significantly elevated, we strongly consider a kidney transplant biopsy. We also see what the TTV load is to see if that provides helpful information.”

Dr. Thomas notes that all these considerations must be individualized to patients, and clinicians must take other factors into consideration, such as adherence, overall drug regimen, and viruses. “What is the total clinical picture?” Dr. Thomas asks, saying, “Because TruGraf and TRAC-ID are tools in your toolbox. But there are all these other traditional tools that we’ve always used that we should include in evaluating the patient.”

Integrating Panel Molecular Monitoring Into Clinical Practice

TruGraf TX with TRAC <0.7 suggests no signs of subclinical rejection or injury. Teams should assess immunosuppression and continue a normal monitoring frequency outside of any other concerns.
TruGraf TX with TRAC ≥0.7 suggests graft injury without immune activation. Teams should investigate immunosuppression and repeat testing and/or consider moving on to an at-need biopsy depending on other factors and test outcomes.
TruGraf Not-TX with TRAC <0.7 suggests subclinical immune activation without current injury. Teams should investigate immunosuppression and repeat testing and/or consider moving on to an at-need biopsy depending on other factors and test outcomes.
TruGraf Not-TX with TRAC ≥0.7 indicates a high likelihood of active rejection. Teams may want to move to a for-cause biopsy.

Biomarker-Guided Conversion: A Practical Path Forward

For post-transplant teams managing belatacept and other immunosuppression conversions, panel diagnostics like TruGraf and TRAC-ID offer practical methods for making data-informed clinical decisions. These tools can help teams reduce risk and improve outcomes. As Dr. Thomas notes, biomarkers are one tool in the post-transplant treatment toolbox, but within a proper clinical framework, they can go a long way to helping teams personalize therapy, detect issues early and support confidence in treatment decisions.

Transplant Genomics is committed to providing clinicians with the tools and data they need to make confident, patient-centered decisions in post-transplant care.

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