Reducing the risk of infection in end-stage kidney failure patients treated by dialysis

After cardiovascular causes, infectious diseases are the next most common cause of death for dialysis patients. The Japanese Society for Dialysis Therapy reported an increased standardized mortality of 7.5-fold [95% confidence limits (CI) 7.3–7.6] for infectious diseases between 2008 and 2009 compared with the general Japanese population. The increased mortality rates for dialysis patients were greatest for sepsis, followed in descending order by peritonitis, influenza, tuberculosis and pneumonia [1]. Patients with chronic kidney disease are more susceptible to some infections, as the azotaemic state alters innate immunity, with reports of reduced monocyte Toll-like receptor 4 expression [2], reduced B-lymphocyte cell populations [3] and impaired polymorphonuclear chemotaxis and phagocytosis [4]. It has also been proposed that changes in the gastrointestinal microbiota, and increased intestinal permeability to endotoxin, lead to a persistent activation of the innate immune system, resulting in the induction of immuneregulatory mediators which then suppress both innate and adaptive immunity [5]. Additionally, immune responses may also be impaired by poor nutritional status, malnutrition and vitamin D deficiency [6]. For many years, it has been recognized that haemodialysis and peritoneal dialysis (PD) patients have a reduced response to vaccination, in terms of developing seroprotective antibody levels, to a number of the commonly available vaccines including hepatitis B, pneumococcus, influenza A H1N1 and tetanus toxoid [7]. The risk of mortality with chest infections in the chronic dialysis patient has been reported to be 14- to 16-fold higher than that for the general population, with >50% of lower respiratory tract infections caused by Streptococcus pneumoniae [8]. Lower respiratory tract infections have additionally been reported to increase the relative risk for cardiovascular events by 3.02 (95% CI: 2.87–3.02) in dialysis patients with pneumonia [9]. Most haemodialysis patients gain fluid between dialysis sessions [10], and this increase in extracellular volume includes lung water. As such, lung water content is increased even in healthy haemodialysis outpatients without any respiratory symptoms prior to dialysis [11]. Whereas it was readily established that the mouth and upper airway are extensively colonized by bacteria, it is only relatively recently that it has been recognized that the lung is also normally colonized. The average person inhales 8000 L of air each day, containing 10 4 –10 6 bacterial cells per cubic metre. The internal surface area of the lung is some 30 times that of the skin and the lung microbiome is determined by the balance between microbial immigration, elimination and the relative growth rates of different bacteria [12]. The proportion of resident to transient microbes remains to be determined in healthy subjects, and it remains to be established how chronic kidney disease and dialysis affect the lung microbiome. Surfactant in the distal alveoli has bacteriostatic activity against some bacterial species, and it is unknown whether this bacteriostatic activity is impaired in dialysis patients. Similarly, other changes in innate and adaptive immunity will affect the risk for pulmonary infections. The lung microbiome is altered by hypoxia [12], and increased water lung content in the dialysis patient will increase hypoxia in dependent areas of the lung. As such these changes may help explain the increased risk of pulmonary infections in dialysis patients. This risk for pulmonary infections appears to be much greater for haemodialysis patients, and although this may be related to greater changes in lung water content during the dialysis week compared with PD patients, haemodialysis patients additionally often travel together to and from dialysis centres and wait together at the start and end of dialysis sessions increasing the risk of respiratory pathogen transmission, whereas PD is a home-based therapy. Inflammatory changes in the lung have been shown to lead to changes in other organs, the so-called organ ‘cross talk’, and the combination of pulmonary inflammation and increased lung water may account for the increased cardiovascular events reported [9]. To reduce the risk IN FOCUS