Low Plasma Level of Cathelicidin Antimicrobial Peptide (hCAP18) Predicts Increased Infectious Disease Mortality in Patients Undergoing Hemodialysis

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 ng/mL 539 +/- 278 and 650 +/- 353 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.