Common Virus May Cause Anemia in Patients with Kidney Disease

Highlights• Kidneys from most patients with chronic kidney disease were positive for active cytomegalovirus infection.• Patients with higher levels of anti-cytomegalovirus antibodies in their blood had lower number of red blood cells.• Cytomegalovirus blocks a protein needed to make a hormone that in turn stimulates red blood cell production.

Cytomegalovirus is carried by approximately 70% of the population.

Newswise — Washington, DC (April 10, 2014) — A virus that is present in most people in a latent state may induce or exacerbate anemia in patients with kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings point to a new therapeutic target for affected individuals.

Chronic kidney disease (CKD) patients and kidney transplant recipients often develop anemia, or low levels of red blood cells. This is often because they do not produce enough erythropoietin (EPO), a hormone that is made in the kidney and stimulates production of red blood cells. Lynn Butler, PhD, Cecilia Söderberg-Naucler, MD, PhD (Karolinska Institute, in Stockholm, Sweden) and their colleagues wondered whether infection with cytomegalovirus (CMV), a type of herpes virus carried by approximately 70% of the population, might play a role in the development of anemia in these patients.

Most people carry CMV for life without any clinical symptoms because the immune system controls the infection; however, under some circumstances the virus can become active, replicate, and cause symptoms. The kidney is a target organ for CMV, and previous reports have shown that an active CMV infection is often present in transplanted kidneys.

Dr. Butler and her colleagues first looked to see if CMV could be detected in kidney biopsies from CKD patients and then investigated if, and how, the presence of such an infection could be linked to the development of anemia.

The team discovered that kidneys from 9 of 13 CKD patients were positive for active CMV infection and that patients with higher levels of anti-CMV antibodies in their blood had lower number of red blood cells.

Additional tests revealed that CMV infection inhibits the ability of cells to produce EPO and that it does this by preventing the production of a protein called hypoxia inducible factor (HIF2α).

“We have established a link between CMV infection and the development of anemia in chronic kidney disease patients. Thus, this virus could provide a target for therapeutic intervention,” said Dr. Butler.

In an accompanying editorial, Michael Seifert, MD and Daniel Brennan, MD (Washington University at St. Louis) lauded the investigators for their thoroughness. “A major strength of this study is the authors’ use of clinical observations, human biospecimens, animal models, and cell culture experiments to conduct true translational research that addresses an important question for clinicians,” they wrote. “We applaud this innovative study,” they added.

Study co-authors include Mensur Dzabic, MD, PhD, Frank Bakker, Belghis Davoudi, Hannah Jeffery, PhD, Piotr Religa, MD, PhD, Krzysztof Bojakowski, MD, PhD, Koonchu-Yaiw, PhD, and Afsar Rahbar, PhD.

Disclosures: The authors reported no financial disclosures.

The article, entitled “Human Cytomegalovirus Inhibits Erythropoietin Production,” will appear online at http://jasn.asnjournals.org/ on April 10, 2014.

The editorial, entitled “Cytomegalovirus and Anemia: Not Just for Transplant Anymore,” will appear online at http://jasn.asnjournals.org/ on April 10, 2014.The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.Founded in 1966, and with more than 14,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.# # #