Urinary levels of a cytokine correlate with renal disease severity.


Researchers say they have discovered a novel biomarker for renal activity in patients with lupus nephritis. The marking, a cytokine called TWEAK, can be measured with a simple urine test.

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“This new urine test may allow us to pick up disease activity earlier or catch a relapsing patient sooner than we have been able to in the past. We may also be able to use this test to monitor response to treatment,” said investigator Chaim Putterman, MD, associate professor of medicine, microbiology, and immunology at Albert Einstein College of Medicine in New York.


Dr. Putterman and his team at Einstein and Ohio State University in Columbus, as well as a research team at Biogen Idec of Cambridge, Mass., led by Jennifer Michaelson, PhD, and Linda Burkly, PhD, discovered that the binding of TWEAK to a receptor called Fn14 induces secretion of pro-inflammatory chemokines. This is considered to be crucial to the pathogenesis of lupus nephritis.


Dr. Putterman and Noah Schwartz, also of Einstein, presented TWEAK data at the 2006 American College of Rheumatology annual meeting suggesting that blocking the binding of TWEAK to its receptor could provide a new approach to treating lupus nephritis. The study found that Fn14, the TWEAK receptor, is expressed on the surface of mesangial cells and podocytes.


Dr. Putterman’s group obtained urine from 83 systemic lupus erythematosus (SLE) patients recruited from Albert Einstein-affiliated lupus clinics and the Ohio SLE Study (OSS), which is headed by Brad Rovin, MD. All patients were scored for the four kidney-related items of the SLE Disease Activity Index; 51 patients were further prospectively classified according to the presence of active or chronic stable disease and severity of renal and non-renal flares.


Urinary TWEAK levels correlated with disease activity, with levels higher in SLE patients with active disease compared with patients who never had renal disease or who had non-active renal disease. TWEAK levels also correlated with severity of renal disease activity. Additionally, TWEAK levels were higher in lupus patients in disease relapse compared with pa-tients with chronic stable disease.

“We have very effective ways of treating lupus nephritis with cyclophosphamide and/or mycophenolate, but sometimes it takes several months until we are sure a patient is responding. Now that there are alternative treatments, we would like to discover an early predictor of a response,” Dr. Putterman said. “So, instead of waiting six months or longer to determine if a patient is responding to cyclophosphamide, we would rapidly change our treatment regimen if we could find out early that it is not helping.”