The Iron Biology Status of Peritoneal Dialysis Patients May be a Risk Factor for Development of Infectious Peritonitis

Abstract

Background Infectious peritonitis is a clinically important condition contributing to the significant mortality and morbidity rates observed in peritoneal dialysis (PD) patients. Although some of the socioeconomic risk factors for PD-associated peritonitis have been identified, it is still unclear why certain patients are more susceptible than others to infection. Methods We examined the molecular components of human peritoneal dialysate (HPD) in an attempt to identify factors that might increase patient susceptibility to infection. Characterization studies were performed on initial and follow-up dialysate samples collected from 9 renal failure patients on PD. Results Our in vitro data showed that peritonitis-causing bacteria grew differently in the patient dialysates. Proteomic analysis identified an association between transferrin presence and infection risk, as peritoneal transferrin was discovered to be iron-saturated, which was in marked contrast to transferrin in blood. Further, use of radioactive iron-labeled transferrin showed peritoneal transferrin could act as a direct iron source for the growth of peritonitis-causing bacteria. We also found catecholamine stress hormones noradrenaline and adrenaline were present in the dialysates and were apparently involved in enhancing the growth of the bacteria via transferrin iron provision. This suggests the iron biology status of the PD patient may be a risk factor for development of infectious peritonitis Conclusions Collectively, our study suggests transferrin and catecholamines within peritoneal dialysate may be indicators of the potential for bacterial growth in HPD and, as infection risk factors, represent possible future targets for therapeutic manipulation.

Proteomic Research in Peritoneal Dialysis

“…Although improvements in PD technology and intensive patient training in aseptic technique have reduced the incidence of skin microbe-associated peritonitis, it remains unclear as to why certain PD patients are more susceptible than others to infection. Aldriwesh et al [87] collected samples from nine patients at PD initiation and later in therapy in order to identify factors that may increase patient susceptibility to infection. They initially found that three bacteria (Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumoniae), typically involved in peritoneal infections, grew in PDE with variability between patients but did not do so when incubated with the PD solution.…”

“…Interestingly, analysis of the iron binding status of peritoneal transferrin found it to be iron-saturated, which indicates no further iron-limitation protection against pathogens such as that created by transferrin in the blood [88]. Upon using radioactive iron-labeled transferrin, peritoneal transferrin was found as a potential direct iron source for the growth of bacteria causing peritonitis [87]. Moreover, adrenalin and noradrenalin were found in PDE and may be involved in enhancement of bacteria growth via transferrin iron provision.…”

“…Therapeutic implications may also follow, the authors having observed that restoring a more iron-restricted environment by addition of iron-free apo-transferrin to PD solution inhibited the growth of PD bacterial pathogens. This approach, which scavenges free iron and has been explored in various clinical conditions [88], might be of use in PD patients as an anti-infective prophylactic measure or adjuvant therapy in case of developed infectious peritonitis [87].…”

“…It can also act as bacteria growth source. [87] 2D SDS-PAGE/MS and iTRAQ EPS 3 to 5 years before EPS: changes in COL1A1, g-actin, CFB and CFI, and SERPINA1. 2 years before EPS: GSN, APOA2, APOA4, and HBB.…”

Inter-Kingdom Signaling of Stress Hormones: Sensing, Transport and Modulation of Bacterial Physiology

“…In Actinobacillus pleuropneumoniae, mutation of the gene encoding TonB2 protein prevents growth stimulation by catecholamines (Li et al, 2015), and in Aeromonas hydrophila, the increase of bacterial growth due to these molecules seems also dependent on TonB2-energy transduction system (Dong et al, 2016). Recently, Aldriwesh et al (2019) showed that Epi and NE present in peritoneal dialysate can enhance the development of bacteria and the infection risk via transferrin iron provision. All these results showed that catecholamines can increase growth of several bacteria, and that this effect may be, in part, closely related to iron homeostasis.…”