OREGON STATE UNIVERSITY

Vitamin D, immune response may reduce fatal infections in dialysis patients

03/23/2009

CORVALLIS, Ore. – Higher levels of a certain antimicrobial protein that’s regulated by vitamin D appear to significantly reduce the risk of death from infection in dialysis patients, a new study has found.

Patients with a high level of this protein were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection, which is a constant concern with dialysis patients. Death from infection is 100 to 300 times higher for dialysis patients than for most people.

The research was done by scientists from the Linus Pauling Institute at Oregon State University, Cedars-Sinai Medical Center, Harvard Medical School and the University of Copenhagen. It was published in Clinical Infectious Diseases, a professional journal.

This protein, called human cathelicidin antimicrobial protein, or hCAP18, is part of the “innate” immune system in humans, a mechanism that helps fight off various bacteria, viruses and fungi even though they have never been encountered before. These “antimicrobial peptides” have been the source of considerable research in recent years, in part because pathogens rarely develop resistance to them.

“The two primary killers of dialysis patients are heart attacks and infections, which often begin around catheters,” said Adrian Gombart, an expert on vitamin D and associate professor in the Linus Pauling Institute. “If hCAP18 is directly responsible for increases in survival, therapies that increase its levels might be a good adjunct to traditional antibiotics to address this problem.”

This study looked at 279 patients across the nation with end-stage renal disease who were being treated with dialysis – a situation facing about 300,000 people in the United States. People with severe kidney disease often have immune systems that are out of balance, as well as low levels of vitamin D, which plays a key role in the immune response. It had been found earlier that administration of active vitamin D analogues to patients undergoing hemodialysis could reduce their mortality rate, but the mechanisms are not understood.

The peptide hCAP18 is of particular interest, Gombart said, because it’s the only known antimicrobial peptide of this type in humans. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis. This peptide is regulated in the body by vitamin D, and it’s believed that vitamin D therapy may be one mechanism that could boost hCAP18 levels.

The study found that plasma levels of hCAP18 in the dialysis patients were on average about half that of healthy individuals, and that those with the very lowest levels were almost four times as likely to die from infection within a year.

Further studies are needed of the mechanisms of disease prevention with these patients, the researchers said, and whether vitamin D or other therapies can raise hCAP18 levels in these patients and improve their overall survival.

This study may also be useful, Gombart said, to help physicians identify dialysis patients who are at greatest risk of infection, and be able to address those problems quickly.

This research was supported by the National Kidney Foundation and the National Institutes of Health.