Circulating Blood Factor Linked to Kidney Failure

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.

The factor could be used to monitor the progression of patients with focal segmental glomerulosclerosis (FSGS) as well as their response to different therapies and it may also be a therapeutic target of future treatments for this difficult-to-treat disease.

A team of scientists at Rush University Medical Center (Chicago, IL, USA) evaluated whether 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.

The study included 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. The main findings were that 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.

In the European patients, with a nephrosis 2, idiopathic, steroid-resistant (NPHS2) mutation had higher suPAR levels than those without a mutation. The authors concluded that, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. Jochen Reiser, MD, PhD, the senior author said, “Anti-suPAR therapies may help reduce the burden of FSGS, since FSGS can recur after kidney transplantation, suPAR removal may also have relevance in the treatment of post-transplant FSGS.” The study was published on November 8, 2012, in the Journal of the American Society of Nephrology (JASN).

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