Circulating Blood Factor Linked with a Leading Cause of Kidney Failure

Released: 2-Nov-2012 9:00 AM EDT
Embargo expired: 8-Nov-2012 5:00 PM EST
Source Newsroom: American Society of Nephrology (ASN)
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Citations doi: 10.1681/2012030302

Findings could help doctors monitor and treat patients with this kidney disease

Highlights
• Most patients with focal segmental glomerulosclerosis, a leading cause of kidney failure, have high levels of a factor called suPAR circulating in their blood.
• suPAR levels could help doctors monitor the disease’s progression as well as patients’ response to different therapies.
• suPAR might be a therapeutic target of future treatments for this difficult-to-treat disease.

Yearly, about 5,000 individuals in the U.S. are diagnosed with focal segmental glomerulosclerosis.

Newswise — Washington, DC (November 8, 2012) — Patients with a disease that is a leading cause of kidney failure tend to have high levels of a particular factor circulating in their blood, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that the factor could be used to monitor the disease’s progression as well as patients’ response to different therapies. It might also be a therapeutic target of future treatments for this difficult-to-treat disease.

Focal segmental glomerulosclerosis (FSGS), which is characterized by scarring of the kidneys, is a devastating disease in both children and adults. Most therapies are not effective, and patients often eventually need to undergo a kidney transplant. Research indicates that high blood levels of a factor called soluble urokinase receptor (suPAR)—which is overproduced in FSGS—plays a key role in the development of the disease. At high concentrations, suPAR binds to and damages kidney podocyte cells, leading to poor kidney filtration and protein excretion in the urine, eventually causing kidney failure.

Jochen Reiser, MD, PhD (Rush University Medical Center) and his colleagues evaluated suPAR levels in the blood of 70 adult FSGS patients from North America, 94 pediatric FSGS patients from Europe, and 150 individuals without the disease. They also analyzed suPAR levels after patients were treated with various drugs.

Among the major findings
• 84% and 55% of FSGS patients in the two different cohorts had elevated suPAR levels in their blood, compared with only 6% of individuals without FSGS.
• After treatment with mycophenolate mofetil, an immunosuppressant, patients had significantly reduced suPAR levels in the blood. They also had reduced protein excretion in the urine and a greater likelihood of experiencing remission.
• Treatment with cyclosporine A, another immunosuppressant, did not produce these effects.

The findings suggest that suPAR blood tests might be used to monitor patients’ disease and their response to treatment. Also, “anti-suPAR therapies may help reduce the burden of FSGS,” said Dr. Reiser. “Since FSGS can recur after kidney transplantation, suPAR removal may also have relevance in the treatment of post-transplant FSGS,” he added.

Study co-authors include Changli Wei, MD, PhD, Howard Trachtman, MD, Jing Li, Chuanhui Dong, PhD, Aaron L. Friedman, MD, Debbie S. Gipson, MD, Frederick Kaskel, MD, PhD, Dagmar-C. Fischer, MD, Jennifer J. Gassman, PhD, June L. McMahan, MD, Milena Radeva, Karsten M. Heil, MD, Agnes Trautmann, MD, Ali Anarat, MD, Sevinc Emre, MD, Gian M. Ghiggeri, MD, PhD, Fatih Ozaltin, MD, Dieter Haffner, MD, and Franz Schaefer, MD.

Disclosures: Changli Wei and Jochen Reiser have issued and/or pending patents on the mechanisms and therapeutics for proteinuric renal diseases. They stand to gain royalties from their future commercialization.

The article, entitled “Circulating suPAR in Two Cohorts of Primary FSGS,” will appear online at http://jasn.asnjournals.org/ on November 8, 2012, doi: 10.1681/2012030302.

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