Cytomegalovirus may exacerbate anemia in chronic kidney disease

Renal cytomegalovirus infection may precipitate or worsen anemia in patients with chronic kidney disease, according to recent findings.

Previous studies have associated the development of anemia with impaired production of erythropoietin (EPO), a glycoprotein hormone that is inhibited by cytomegalovirus (CMV) and which stimulates red blood cell production.

In the study, researchers acquired kidney tissue biopsies or serum samples from 13 chronic kidney disease patients in stage IV renal failure, measured by glomerular filtration rate.

Nine of the 13 patients tested positive for renal human CMV immediate-early proteins. Two patients’ blood samples were confirmed to be CMV immunoglobulin G-negative, and also had biopsies that were negative for human CMV protein staining. None of the patients demonstrated signs of active CMV infection.  

The researchers then analyzed the relationship between CMV antibodies and anemia by examining serum samples for CMV IgG and for hematological factors. They found that there was an inverse relationship between CMV IgG and red blood cell count, but neutrophil and lymphocyte counts were not altered by CMV.

To assess the effect of renal CMV on the cellular production of EPO, the researchers injected human EPO-producing cells with CMV clinical strain VR1914 and cultured them for 24 hours or 7 days.

Researchers observed that at 24 hours post-inoculation, roughly 70% of EPO-producing cells were positive for CMV immediate-early proteins, but not for late proteins. At 7 days after inoculation, both CMV immediate-early and late proteins were seen in roughly 60% of EPO-producing cells. However, the intensity of the CMV immediate-early staining was attenuated at the 7-day time point compared with 24 hours post-inoculation. In EPO-producing cells treated with umbilical-vein-inactivated CMV, no immediate-early or late proteins were seen at either 24 hours or 7 days.

The researchers also determined that CMV inhibits production of EPO through the hypoxia-induced transcription factor-2 alpha.

According to study investigator Lynn Butler, PhD, of the Karolinska Institute in Stockholm, these findings indicate that CMV, which is carried asymptomatically by approximately 70% of the population, might be a valuable target for future chronic kidney disease-related anemia treatments.

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

Disclosure: The researchers report no relevant financial disclosures.