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.

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).