Genetic test uses qPCR to cut kidney transplant rejection

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Genetic test uses qPCR to cut kidney transplant rejection

A team of researchers from the USA, Spain and Mexico have used qPCR (quantitative polymerase chain reaction) to help to develop a genetic blood test that could spot those people at risk of rejecting their transplanted kidney up to three months before it happens, providing an potential alternative to invasive biopsies.

kidney transplant

Kidney transplants are life-changing operations and are generally very successful – US statistics show that 97% are still working after a month, 93% after a year, and 83% after three years. However, some transplants are damaged because of an immune response. This acute rejection reduces the efficacy of the kidney and therefore the patients’ quality of life, and can lead to transplant failure. This is currently detected by changes in creatinine levels, which only occurs after significant damage, and confirmed through a biopsy, an invasive and unpleasant process. Predicting who might be at risk, or detecting very early stage acute rejection, will help doctors be able to put preventative strategies in place.

The team measured expression of 43 genes, including using quantitative real-time PCR (QPCR), in 558 blood samples from 436 adult and paediatric kidney transplant patients in the US, Mexico, and Spain. The genes were selected because of changing expression profiles during kidney rejection, and the patients were recruited as part of the Assessment of Acute Rejection in Renal Transplantation (AART) study. The researchers found a 17-gene set, dubbed the Kidney Solid Organ Response Test (kSORT), in 143 samples. They validated the genes selected in 124 independent samples.

“We have found a set of genes in blood that pick up inflammation and acute rejection in different solid organ transplants,” says Minnie Sarwal, professor of transplant surgery at UCSF. “This is the first assay of its kind that can provide a sensitive readout of very early rejection and inflammation in the organ, which cannot be picked up by any other blood test on the market.”

The test correctly identified 39 of 47 positive results (patients with acute rejection) and 87 of 96 negative results (patients without rejection). The kSORT also predicted acute rejection up to three months earlier than detection by biopsy, the gold standard test, independent of age, time after transplant and sample source.

“The kSORT assay could be a potential breakthrough in transplant medicine,” says Elaine Reed, director of the University of California Los Angeles Immunogenetics Center. “This multicenter study reflects a wide cohort of patients nationally and internationally, and the results hold real promise in identifying future patients at risk for rejection.”

As a final step, the team created an algorithm that would be able to classify patients as high or low risk. As Oriol Bestard, nephrologist, University Hospital of Bellvitge, explains, the test could allow doctors to adapt immunosuppressive therapy in patients at higher risk of failure to prevent immune damage and graft failure.

“This report validates the kSORT assay to detect risk of acute rejection in renal transplant patients, giving it the potential to become a simple, robust and clinically applicable blood test that will provide each patient with an immune risk ‘window’ for optimal immunosuppression delivery,” says Sarwal.

At the moment, kSORT does not discriminate between cell-mediated and antibody-mediated rejection, which require different forms of treatment, and so this will require further development. The test will be further assessed in prospective clinical observational and interventional trials. Two prospective trials in the European Union and Mexico already are under way, with kSORT being used for immune monitoring of the kidney transplant patients through serial blood tests.

The research was carried out at the Bellvitge Biomedical Research Institute (IDIBELL), the University Hospital of Bellvitge, the University of California San Francisco, Cincinnati Children’s Hospital, California Pacific Medical Center, University of Pittsburgh, University Emory and Stanford University (USA) and the Children’s Hospital of Mexico Federico Gomez, and was published in PLOS Medicine.

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