Chronic kidney disease (CKD) patients and kidney transplant recipients develop anemia, or low red blood cell levels, often. This occurs frequently because their kidneys can’t produce enough erythropoietin (EPO), a hormone that stimulates red blood cell production. A new study found that cytomegalovirus (CMV), a common herpes virus that approximately 70 percent of the population carries, may induce or exacerbate anemia in kidney patients.
Cytomegalovirus Lowers Red Blood Cells
Most people have CMV for life without any clinical indicators because their immune systems control the infection. But under some circumstances, the virus can become active, replicate and cause problems. The kidneys are focal organs for cytomegalovirus, and previous reports showed that an active infection is present in transplanted kidneys often.
The researchersdetected active CMV infections in almost 75 percent of CKD patients’ kidney biopsies.
Subjects with higher levels of anti-cytomegalovirus antibodies in their blood had lower numbers of red blood cells. Additional tests revealed that CMV infection inhibits the ability of cells to produce EPO by preventing the production of the hypoxia inducible factor (HIF2α) protein. Systemic murine cytomegalovirus infection also decreased serum EPO levels in mice.
“We have established a link between CMV infection and the development of anemia in chronic kidney disease patients,” said researcher Dr. Lynn Butler, Ph.D., of the Karolinska Institute in Stockholm, Sweden. “Thus, this virus could provide a target for therapeutic intervention.”
Michael Seifert, M.D., and Daniel Brennan, M.D., of Washington University in St. Louis, Mo., 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 said. “We applaud this innovative study.”
The Kidney Transplant Factor
Cytomegalovirus is one of the most important infections in renal transplant recipients. Exposure to the virus increases with age in the general population and is present in more than two-thirds of donors and recipients prior to transplantation.
If the transplant recipient doesn’t already have cytomegalovirus, the donor can transmit it through blood transfusion or the transplanted kidney. The concurrent administration of immunosuppressive drugs to prevent rejection increases the risk of clinically relevant CMV disease further. Induction, or initial, therapy is the principal factor in increased disease risk. Thus, both the recipient and the donor need routine tests checking for anti-CMV antibodies prior to transplantation.
Using data from the United States Renal Data System, a study showed that cytomegalovirus is a significant underlying cause of morbidity and mortality in renal transplants. Donor and recipient CMV antibody status was available for over 17,000 deceased-donor renal transplant recipients. Based on a multivariate analysis, CMV-positive patients had significantly higher incidences of cytomegalovirus disease, transplant loss and overall costs, compared to CMV-negative recipients.
A prospective single-center study of almost 500 patients who didn’t receive induction therapy or cytomegalovirus preventive measures examined the impact of this viral infection on overall mortality. Scientists monitored patients biweekly for CMV antigenemia (antigens circulating in the blood) for 100 days and followed up for a median length of time of 66 months. Despite the absence of induction and maintenance immunosuppressive therapy, researchers detected CMV antigenemia in over 60 percent of patients in the first 100 days after transplant. Compared to those without cytomegalovirus, scientists associated CMV disease with a 2.5 relative risk of overall mortality. They linked asymptomatic cytomegalovirus infection with a 2.9 relative risk of overall mortality.
Typical CMV Symptoms
According to the Mayo Clinic, cytomegalovirus spreads from one person to another through body fluids such as blood, saliva, urine, semen and breast milk. Your body retains the virus for life, but CMV remains dormant usually in healthy carriers. Most don’t know they have cytomegalovirus because it causes few if any indicators in people who are well otherwise.
Right after infection, some adults with weakened immune systems may have symptoms similar to mononucleosis including fatigue, fever and muscle aches. Other signs of infection may include:
Ulcers in the digestive tract, possibly causing bleeding
Inflammation of the brain (encephalitis)
Visual impairment and blindness
A study characterized the symptoms and outcome of 297 patients with CMV infections in a large cohort of 1129 kidney transplant recipients. Gastrointestinal symptoms were common, especially in patients with primary cytomegalovirus infection. Bone marrow suppression, hepatopathy liver dysfunction and malaise occurred less frequently.
The researchers found gastrointestinal symptoms in 58 percent and fever in 47 percent of patients with primary CMV disease, compared to 46 and 27 percent of patients with symptomatic cytomegalovirus reactivation. They detected leukopenia (low white blood cell count) or thrombocytopenia (low blood platelet count) in only 17-28 percent and malaise in 9-10 percent of patients. The study team confirmed tissue-invasive CMV gastroenteritis in 11 percent and cytomegalovirus pneumonia in just 1 percent of CMV disease patients.
Diagnosis and Treatment
If you have a weakened immune system, cytomegalovirus is a cause for concern. Your doctor can order blood tests to discover the presence of antibodies that your immune system creates when you have CMV. Other virus detection methods include polymerase chain reaction tests from blood or other body fluids, cultures and tissue biopsies. Valcyte and are prescription antiviral medications that interfere with viral RNA (ribonucleic acid) synthesis, stopping cytomegalovirus from reproducing.