Chronic kidney disease (CKD) is a major health burden: 10-15% of the general population show an impairment of kidney function. CKD provides a strongly increased risk for infections, as well as high cardiovascular risk. Accordingly infection is a major cause of mortality in CKD patients. PCSK9 is a novel but pivotal regulator of cholesterol metabolism and PCKS9 inhibitors represent a new, potent class of drugs for treatment of hypercholesterolemia. Shortly after appraisal as critical player in lipid metabolism, PCSK9 has been also recognized as important player in both viral and bacterial infection, sepsis and septic shock. PCSK9 inhibition likely increases LPS clearance via increased LDLR expression and, in mice, PCSK9 deficiency confers protection against systemic bacterial dissemination, organ pathology, and tissue inflammation in lung and liver. Conversely, PCSK9 inhibition possibly increases HCV susceptibility via increasing CD81 expression and worsens inflammation by upregulation TNFα and IL1β. This makes PCSK9 an interesting and potentially druggable candidate modifying susceptibility to infections in CKD patients. We therefore aim to investigate the role of PCSK9 levels as prognostic or modifying factor in the development of infection and sepsis in chronic kidney disease patients. In addition we will perform a genome-wide association study to identify additional genes besides the PCSK9 gene that show an association with PCSK9 concentrations. These studies will be done in the GCKD study which is a prospective observational cohort study with more than 5000 individuals and one of the currently largest studies on CKD worldwide. Up to now we have follow-up data from the first 4 years of follow-up with more than 600 patients who experienced more than 900 hospitalizations due to infections. This number increases dramatically and during the next 9 month the six-year follow-up data will become available.
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