Infections in patients with chronic kidney disease : patterns, outcomes and the role of vitamin D for future prevention

Abstract: Background: Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. Patients with CKD are at high risk of infections. Frequent episodes of infections with greater use of antibiotics might put this population at risk of infections caused by resistant organisms. Thus, infection issues in patients with CKD could be related to another public health problem - antibiotic resistance. Aim: To investigate the antibiotic resistant patterns of pathogens responsible for infections, ascertain short-term and long-term patient outcomes during and after hospitalizations with infections and explore the role of vitamin D for infection prevention in patients with CKD. Methods: The thesis consists of two observational studies (Paper I & II), one cohort study (Paper III) and one systematic review and meta-analysis (Paper IV). Paper I, II & III explored the association between kidney function (defined as estimated glomerular filtration rate, eGFR) and various outcomes. These outcomes included microbial pattern (Paper I), prevalence of infections with multi-drug resistant organisms (MDROs) in the first positive microbial cultures (Paper I), intensive care unit admission (Paper II), length of hospital stay (Paper II), medical expense (Paper II), and mortality (Paper II & III). These were assessed in patients hospitalized with infections, using electronic medical records from four hospitals from 2012 to 2015 in China. Paper IV obtained data from existing literature to explore the association of infections with vitamin D status or use of vitamin D in patients treated with long-term dialysis. Results: In adult patients hospitalized with infections, the proportion of Gram-negative bacteria decreased while the proportion of Gram-positive bacteria increased across eGFR strata. Compared with the reference eGFR, lower eGFR was associated with: higher odds of infections by MDROs (19% and 41% higher in those with eGFR between 30-59 ml/min/1.73 m2 and eGFR <30 ml/min/1.73 m2, respectively) (Paper I); more than twofold higher adjusted odds of ICU admission, longer median length of hospital stay (P< 0.001), inferred 20.0% higher costs in those with eGFR< 60 ml/min/1.73 m2 (P< 0.001) (Paper II); progressively increased risks of cardiovascular mortality (subdistribution hazard ratio [SHR] 2.15 for eGFR 30-59 mL/min/1.73m2; SHR 3.19 for eGFR<30 mL/min/1.73m2) (Paper III). In the systematic review of vitamin D and infections in patients treated with long-term dialysis, the risk of composite infections was 39% lower in those with high/normal levels of 25-hydroxy vitamin D than that in those with low levels. Compared to those who did not use vitamin D, the pooled adjusted risk of composite infection was 41% lower in those who used vitamin D (Paper IV). Conclusions: CKD patients hospitalized with infections have a higher risk of infections by MDROs, poorer in-hospital outcomes resulting in higher medical costs and increased risk of cardiovascular mortality in the long-run. Use of vitamin D to achieve high/normal serum levels of 25(OH)-vitamin D might help lowering the risk of infections in maintenance dialysis patients. Further research is needed to investigate the potential role of vitamin D therapy in infection prevention among non-dialysis dependent CKD patients.