Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis

Clin Infect Dis. 2009 Feb 15;48(4):418-24. doi: 10.1086/596314.

Abstract

Background: Human cathelicidin antimicrobial protein (hCAP18) is an antimicrobial and immunomodulatory peptide that has pleiotropic effects and is transcriptionally regulated by vitamin D. Because the administration of vitamin D analogues has been linked to decreased mortality among patients with end-stage renal disease, we hypothesized that low hCAP18 levels would identify those who are at increased risk of death attributable to infection while undergoing hemodialysis.

Methods: We performed a case-control study nested in a prospective cohort of patients (n = 10,044) initiating incident hemodialysis. Case patients (n = 81) were those who died of an infectious disease within 1 year; control patients (n = 198) were those who survived at least 1 year while undergoing dialysis.

Results: Mean (+/-SD) baseline levels of hCAP18 in case patients and control patients were 539 +/- 278 ng/mL and 650 +/- 343 ng/mL, respectively (P = .006). hCAP18 levels had a modest correlation with 1,25-dihydroxyvitamin D levels r = 0.23; P = .053) but not with 25-hydroxyvitamin D levels r = -0.06; P = .44). Patients with hCAP18 levels in the lowest tertile had a 2-fold increased risk (odds ratio, 2.1; 95% confidence interval, 1.2-3.5) of death attributable to infection; after multivariable adjustment, this relationship remained statistically significant (odds ratio, 3.7; 95% confidence interval, 1.2-11.2).

Conclusions: In individuals initiating chronic hemodialysis, low baseline levels of hCAP18, a vitamin D-regulated antimicrobial protein, are independently associated with an increased risk of death attributable to infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimicrobial Cationic Peptides / blood*
  • Case-Control Studies
  • Cathelicidins
  • Cohort Studies
  • Communicable Diseases / mortality*
  • Female
  • Humans
  • Male
  • Renal Dialysis / adverse effects*
  • Risk Factors*
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D