In some kidney diseases, patients have high blood levels of a protein that blocks blood vessel repair, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). 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. Researchers have wondered what factors play a role in determining whether patients’ bodies can repair this damage.
To investigate, Sandrine Le Roux, PhD, Fadi Fakhouri, MD, PhD (Institute of Transplantation Urology Nephrology, in Nantes, France), and their colleagues examined the blood of 81 patients with ANCA-associated vasculitis, 21 patients with other types of kidney disease, and 18 healthy individuals.
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.
“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,” said Dr. Fakhouri. “Inhibiting Flt1 may help improve blood vessel repair in some kidney disease patients and thus reduce their risk of progression to kidney failure,” he added.
Study co-authors include Alexandre Dufay, MD, Mélanie Néel, Emmanuelle Meffray, Maryvonne Hourmant, MD, PhD, Béatrice Charreau, PhD (Institute of Transplantation Urology Nephrology, in Nantes, France); Ruth Pepper, MD, PhD, Alan D Salama MD, PhD (University College London, Royal Free Hospital, in London, England); Etienne Larger, MD, PhD, Noël Lamandé (Collège de France, in Paris); Marie Rimbert, MD, PhD, Régis Josien, MD, PhD, Mohamed Hamidou, MD (CHU de Nantes, in Nantes, France); and H. Terence Cook, PhD (Imperial College, London, England).
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, including Wegener’s granulomatosis and microscopic polyangiitis, is a multisystem autoimmune syndrome characterized by vasculitis predominantly affecting microscopic vessels and circulating autoantibodies to neutrophil cytoplasmic antigens.
“ANCA-associated vasculitis” are Wegener’s Granulomatosis, Micropolyarteritis and its renal-limited variant (previously called idiopathic necrotizing glomerulonephritis).
According to the “Chapel Hill Consensus Conference” classification, ANCA-associated vasculitis is characterized by prevalent involvement of small-size vessels, whereas medium and large-size artery involvement is the marker of Polyarteritis Nodosa.
However, the vessel size-based classification is not always powerful enough, because also in ANCA-associated vasculitis the involvement of medium and large-size arteries is possible. Therefore, the presence of necrotizing extracapillary glomerulonephritis that is always absent in Polyarteritis Nodosa has become the distinctive marker of ANCA-associated renal vasculitis.
Small vessel vasculitis is morphologically defined by massive necrosis of the vascular wall with endo- and peri-vascular inflammatory infiltrates. This lesion should be the diagnostic hallmark of the disease, but is histologically detected in only 20-30% of cases, confirming the diagnostic importance of necrotizing extracapillary nephritis. Furthermore, a similar arteritis can be found in other diseases, such as anti-GBM antibody disease, HS nephritis, cryoglobulinemic nephritis and lupus nephritis.
Disclosures: The authors reported no financial disclosures.
The article, entitled “Elevated Soluble Flt1 Inhibits Endothelial Repair in PR3-ANCA-Associated Vasculitis,” will appear online at http://jasn.asnjournals.org/ on Thursday, October 27, 2011, doi:10.1681/ASN.2011060858.
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Substance in the blood blocks repair and contributes to kidney failure
* Patients with an autoimmune disease called anti-neutrophil cytoplasmic antibody-associated vasculitis produce antibodies that damage blood vessels in the kidneys.
* Patients with the disease harbor elevated blood levels of the protein Flt1, which hinders blood vessel repair.
* Inhibiting Flt1 may help prevent kidney failure in the 1:50,000 patients around the world who have anti-neutrophil cytoplasmic antibody-associated vasculitis, plus those with other more frequent diseases involving blood vessels in the kidneys.