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

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.

Conflict of interest statement

Potential conflicts of interest. All authors: no conflicts.

Figures

Figure 1.

Percentage of individuals in each tertile of human cathelicidin antimicrobial protein (hCAP18) levels who survived for at least 1 year while undergoing hemodialysis (control patients). The remaining subjects died because of infection within 1 year after initiation of hemodialysis (case patients). Individuals within the lowest tertile of hCAP18 levels had a lower chance of survival than did subjects in tertiles 2 or 3 (P = .007). There was no significant difference in mortality between tertiles 2 and 3 (P = .74). Tertiles are based on the distribution of hCAP18 levels among control patients. Tertile 1 hCAP18 levels, 129–487 ng/mL (n = 110); tertile 2 hCAP18 levels, 488–729 ng/mL (n = 87); tertile 3 hCAP18 levels, 732–2856 ng/mL (n = 82).