Blood Biomarker Blocks Repair and Contributes to Kidney Failure

In some kidney diseases, patients have high blood levels of a protein that blocks blood vessel repair and inhibiting the protein may reduce patients' risk of developing kidney failure.

Patients with an autoimmune kidney disorder called anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis produce antibodies that damage blood vessels in the kidneys and these antibodies can be measured in their sera.

At the Institute of Transplantation Urology Nephrology (Nantes, France) scientists examined the blood of 81 patients with ANCA-associated vasculitis, 21 patients with other types of kidney disease, and 18 healthy individuals.

They measured the amount of the protein soluble vascular endothelial growth factor receptor 1 (Flt1) in the serum. Circulating Flt1 and complement component 5 (C5a) were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits.

The investigators found that compared with others in the study, patients with ANCA-associated vasculitis harbor elevated blood levels of the molecule Flt1, which hinders the repair of blood vessels. As a result, their bodies may not be able to fix damaged blood vessels, setting them on a path of continued disease progression. The ELISA kits used are products of R&D Systems (Minneapolis, MN, USA).

Serum levels of soluble Flt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti-proteinase-3 (PR3) monoclonal and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of soluble Flt1 from monocytes, whereas anti-myeloperoxidase (MPO) monoclonal or polyclonal antibodies did not.

Fadi Fakhouri, MD, PhD, the lead author of the study said, "Our data suggest that in some kidney diseases, not only are blood vessels damaged, but their repair is also impaired by an increase of Flt1 in the blood. Inhibiting Flt1 may help improve blood vessel repair in some kidney disease patients and thus reduce their risk of progression to kidney failure." The study was published on October 27 2011, in the Journal of the American Society Nephrology.

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