Urine Test May Help Diagnose Life-Threatening Kidney Damage in Transplant Patients
September 19, 2007
| A team of investigators at Virginia Commonwealth University has developed a urine test that could help identify prospective transplant patients who might be at risk of developing a life-threatening kidney condition after surgery. The condition is known as chronic allograft nephropathy. “In many cases, we are not able to detect the condition until it is really too late to save the transplanted kidney,” said Valeria R. Mas, PhD, director of molecular transplant research and co-author of the genetic study published in Molecular Medicine. “We’ve been looking for molecular markers in urine that can detect earlier this condition. This is a problem we have to resolve in order to improve graft survival.” Patients who undergo kidney transplant have high chances of developing chronic allograft injury in the transplanted kidney, which ultimately will lead to organ dysfunction. Interstitial fibrosis and tubular atrophy in renal allografts are the major hallmarks of progressive graft dysfunction, with the result of a continuous decrease in graft survival after a year post-transplantation. Recently, improvements in drugs that shut down the natural body’s immune response and protect against organ rejection have made a significant impact in lowering a patient’s risk for acute rejection and improving long-term graft survival. Now, the “graft” life-threatening problem – chronic allograft nephropathy -- can sneak up months, even years later with minimal or no symptoms. The first successful kidney transplant took place more than 50 years ago. This was done without immunosuppressive medicines, which were used a decade later to preserve transplanted organs. Medicines to prevent acute rejection have gotten better over time. And these advances prevented acute rejection but do not have much effect on the development of chronic kidney damage. Dr. Mas said that the mechanisms involved in triggering this condition are related to many different factors and that, if it is identified early enough, future interventions at the molecular level may stop or delay it. “We are trying to identify early molecular markers of this chronic condition in urine,” said Dr. Mas. Today, the gold standard is an invasive technique: a kidney biopsy. What’s more, “even when we are not seeing histological damage, under the microscope the disease can be progressing.” The scientists studied RNA expression in urine samples collected from kidney transplant recipients with chronic allograft nephropathy. This condition is also referred to as tubular atrophy and intertitial fibrosis. The study included 95 patients and 111 samples, and they were divided into several groups: those with stable kidney function and no protein in urine, those patients with normal creatinine levels and proteinuria, and those with chronic allograft nephropathy diagnosed through a biopsy. A characteristic pattern of mRNA expression identified in patients with chronic allograft nephropathy suggests that this technique might be useful to identify early graft damage and to utilize preventive treatment. Based on the results of the study, urine genetic markers may be able to predict earlier changes in the graft, anticipating conventional pathology, Mas said. They are now conducting a prospective study to see how markers change over time. Over 200 transplant recipients will be tracked through repeated urine samples over a two-year period. “Chronic allograft dysfunction is the end-result of a series of time-dependent insults to the transplanted kidney resulting in permanent damage and loss of nephrons, the structural and function units of the kidney. A major challenge in the future of renal transplantation is to identify distinct and identifiable triggers, to understand the biology of the process, and to develop new therapeutic options” said Daniel G. Maluf, MD, an associate professor of surgery and transplant surgeon at Virginia Commonwealth. A co-investigator in the study, he added that patients with long-term renal dysfunction must return to dialysis and start looking for a donor for another kidney transplant. According to the Organ Procurement and Transplant Network there were 17,000 kidney transplants in 2006. Today, there are more than 77,000 Americans waiting for a donor kidney, and this number get larger every year. About Molecular Medicine Molecular Medicine is a research journal published by The Feinstein Institute for Medical Research. Located in Manhasset, NY, The Feinstein is home to international scientific leaders in Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. Part of the North Shore-LIJ Health System, The Feinstein Institute ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. For more information, please visit www.FeinsteinInstitute.org or www.molmed.org. Media Contact: Jamie Talan - 516-562-1232 |