Gene findings may make this possible.


Researchers have identified a gene signature that may enable clinicians to distinguish which renal transplant recipients could be eligible for a progressive decrease in their immunosuppressive medications and who needs to stay on their current dose.

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“This may be a very exciting development because it may be possible to use a non-invasive test as a means to safely allow for customized immunosuppression, which will help lower patient care costs and lower patient morbidity,” said Minnie Sarwal, MD, PhD, a pediatric nephrologist at Lucile Packard Children’s Hospital and associate professor of pediatrics at Stanford University School of Medicine in Stanford, Calif.


“There could be huge cost savings. We are not just going to minimize the immunosuppressive drugs and the cost of the drugs, but we will also help lower the risk for malignancies and infections, which will decrease patient morbidity.”  


Dr. Sarwal and her collaborators in France, Canada, China, and the Netherlands analyzed blood gene expression profiles from renal transplant patients and healthy individuals. The transplant recipients were divided into three groups: stable transplant patients on anti-rejection medications (22 patients); patients with chronic rejection but with stable graft function (36 patients); and “operationally” tolerant patients who were not on any immunosuppression therapy for at least three years while still retaining their donor organ (12 patients).  


The investigators, who have published their findings in the advance online edition of the Proceedings of the National Academy of Sciences, conducted a subset gene microarray analysis where three-class comparison of the different groups of patients identified a “tolerant footprint” of just 49 genes from about 30,000 sampled genes.


The researchers found that 33 of the 49 genes correctly segregated tolerance (99% specificity) and chronic rejection phenotypes (86% specificity). Overall, the researchers found a gene signature that was shared with 1 of 12 patients on triple immunosuppression therapy (8%) and 5 of 10 (50%) on stable low-dose steroid monotherapy.  

“We anticipate that within a few years that we may be able to apply this as a real-time blood test for all renal transplant patients,” Dr. Sarwal told Renal & Urology News. “We may be able to order it as a test on a frequent basis, possibly every month, and it would allow the patients and their physician to customize their immunosuppression. We think we are in a new era because for the first time we can start to differentiate the patient requirements for immunosuppression for maintaining stability of their organ. For the first time we can customize immunosuppression for the patient. We used to think one size fit all.”