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Advances in organ surveillance may reduce costs, risk of rejection

Patients who received one of the 21,167 kidney transplants performed in the United States last year no doubt want to ensure their new organ stays healthy, ie, rejection free. Even when patients stick to their prescribed immunosuppressive drug regimen, however, data show 10% to 20% of patients will experience at least one episode of rejection. In most cases, it occurs in the first 6 months of the transplant.

Mark E. Neumann

Traditionally, the ways to detect that a transplanted kidney is failing is by monitoring eGFR and looking for signs like decreased urine output, fatigue and loss of appetite. New technology, however, is giving transplant physicians alternatives. Several companies have available or have in the product pipeline blood tests that would give an early warning sign that an organ might be showing signs of rejection.

Care DX received approval for a CMS reimbursement code for its AlloSure blood test in October 2017. Clinicians can use the test to identify fragmented, donor-derived, cell-free DNA (dd-cfDNA). When graft injury occurs, dd-cfDNA increases in the blood. The company says the test is more accurate than serum creatinine in the diagnosis of rejection and does not require donor or recipient genotyping.

Natera Inc. has also developed a dd-cf DNA assay to detect allograft rejection earlier.

“The analytical validation study clearly shows that Natera’s donor-derived cell-free DNA assay for detecting the risk of kidney transplant rejection is highly accurate and precise and demonstrates superior performance (coefficient of variation up to five-times better) than previously published studies,” Allison Ryan, PhD, vice president of data science at Natera, told Nephrology News & Issues.

Ryan said the precise measurement of donor fraction in cf DNA is a more accurate biomarker for detecting organ rejection than eGFR, which is the standard of care for non-invasive organ testing. “The current tools for diagnosing organ transplant rejection are either invasive (biopsies) or inaccurate (serum creatinine), creating a strong unmet need for better diagnostic tools to improve patient management and outcomes,” she said.

Transplant Genomics Inc. recently announced results using its TruGraf biomarker were published in Transplant Proceedings. The reports describe a series of retrospective and prospective studies conducted in seven transplant centers.

“Based on the comprehensive clinical and analytical validation data published to date, and our results from routine clinical diagnostics, we suggest that broad utilization of the TruGraf v1 blood test has the potential to have a significant positive impact on patient care as a tool to support treatment decisions in managing the health of kidney transplant,” M. Roy First, MD, and colleagues wrote in one of the studies.

“Both retrospective and prospective studies of decision impact revealed that TruGraf testing supported clinician’s decisions regarding patient management in approximately 87% of cases,” the company said in a press release.

Renalytix AI plc, a developer of artificial intelligence-enabled clinical diagnostics for kidney disease, has formed a core investigator group to support clinical and regulatory pathways for a portfolio of new products. The new division, called FractalDx, will be part of the extended RenalytixAI pipeline following the introduction of KidneyIntelX in 2019 for the diagnosis of fast-progressing chronic kidney disease. The company said in a press release that the product portfolio also includes a range of advanced diagnostic tests that are expected to aid in accurate dosing of immune-suppression therapy and in making significant improvements in the identification of and monitoring for kidney transplant rejection.

“There are major unmet needs that limit the survival and effectiveness of kidney transplantation,” Christian P. Larsen, MD, DPhil, a professor of surgery in the division of transplantation at Emory University, said in a press release. “It is important that we develop the next generation of diagnostics and determine how best to incorporate them into the care team workflow to reduce risk and maximize the benefit from immunosuppressive therapy for our transplant recipients.”

Patients who received one of the 21,167 kidney transplants performed in the United States last year no doubt want to ensure their new organ stays healthy, ie, rejection free. Even when patients stick to their prescribed immunosuppressive drug regimen, however, data show 10% to 20% of patients will experience at least one episode of rejection. In most cases, it occurs in the first 6 months of the transplant.

Mark E. Neumann

Traditionally, the ways to detect that a transplanted kidney is failing is by monitoring eGFR and looking for signs like decreased urine output, fatigue and loss of appetite. New technology, however, is giving transplant physicians alternatives. Several companies have available or have in the product pipeline blood tests that would give an early warning sign that an organ might be showing signs of rejection.

Care DX received approval for a CMS reimbursement code for its AlloSure blood test in October 2017. Clinicians can use the test to identify fragmented, donor-derived, cell-free DNA (dd-cfDNA). When graft injury occurs, dd-cfDNA increases in the blood. The company says the test is more accurate than serum creatinine in the diagnosis of rejection and does not require donor or recipient genotyping.

Natera Inc. has also developed a dd-cf DNA assay to detect allograft rejection earlier.

“The analytical validation study clearly shows that Natera’s donor-derived cell-free DNA assay for detecting the risk of kidney transplant rejection is highly accurate and precise and demonstrates superior performance (coefficient of variation up to five-times better) than previously published studies,” Allison Ryan, PhD, vice president of data science at Natera, told Nephrology News & Issues.

Ryan said the precise measurement of donor fraction in cf DNA is a more accurate biomarker for detecting organ rejection than eGFR, which is the standard of care for non-invasive organ testing. “The current tools for diagnosing organ transplant rejection are either invasive (biopsies) or inaccurate (serum creatinine), creating a strong unmet need for better diagnostic tools to improve patient management and outcomes,” she said.

Transplant Genomics Inc. recently announced results using its TruGraf biomarker were published in Transplant Proceedings. The reports describe a series of retrospective and prospective studies conducted in seven transplant centers.

“Based on the comprehensive clinical and analytical validation data published to date, and our results from routine clinical diagnostics, we suggest that broad utilization of the TruGraf v1 blood test has the potential to have a significant positive impact on patient care as a tool to support treatment decisions in managing the health of kidney transplant,” M. Roy First, MD, and colleagues wrote in one of the studies.

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“Both retrospective and prospective studies of decision impact revealed that TruGraf testing supported clinician’s decisions regarding patient management in approximately 87% of cases,” the company said in a press release.

Renalytix AI plc, a developer of artificial intelligence-enabled clinical diagnostics for kidney disease, has formed a core investigator group to support clinical and regulatory pathways for a portfolio of new products. The new division, called FractalDx, will be part of the extended RenalytixAI pipeline following the introduction of KidneyIntelX in 2019 for the diagnosis of fast-progressing chronic kidney disease. The company said in a press release that the product portfolio also includes a range of advanced diagnostic tests that are expected to aid in accurate dosing of immune-suppression therapy and in making significant improvements in the identification of and monitoring for kidney transplant rejection.

“There are major unmet needs that limit the survival and effectiveness of kidney transplantation,” Christian P. Larsen, MD, DPhil, a professor of surgery in the division of transplantation at Emory University, said in a press release. “It is important that we develop the next generation of diagnostics and determine how best to incorporate them into the care team workflow to reduce risk and maximize the benefit from immunosuppressive therapy for our transplant recipients.”