Endotoxaemia in Haemodialysis: A Novel Factor in Erythropoetin Resistance?

Background/Objectives Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients. Methodology/Principal Findings 50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis. Conclusions This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin

An Evidence-Based Theory About PRO Use in Kidney Care: A Realist Synthesis

Background: There is international interest on the use of patient-reported outcomes (PROs) in nephrology. Objectives: Our objectives were to develop a kidney-specific program theory about use of PROs in nephrology that may enhance person-centered care, both at individual and aggregated levels of care, and to test and refine this theory through a systematic review of the empirical literature. Together, these objectives articulate what works or does not work, for whom, and why. Methods: Realist synthesis methodology guided the electronic database and gray literature searches (in January 2017 and October 2018), screening, and extraction conducted independently by three reviewers. Sources included all nephrology patients and/or practitioners. Through a process of extraction and synthesis, each included source was examined to assess how contexts may trigger mechanisms to influence specific outcomes. Results: After screening 19,961 references, 84 theoretical and 34 empirical sources were used. PROs are proposed to be useful for providing nephrology care through three types of use. The first type is use of individual-level PRO data at point of care, receiving the majority of theoretical and empirical explorations. Clinician use to support person-centered care, and patient use to support patient engagement, are purported to improve satisfaction, health, and quality of life. Contextual factors specific to the kidney care setting that may influence the use of PRO data include the complexity of kidney disease symptom burden, symptoms that may be stigmatized, comorbidities, and time or administrative constraints in dialysis settings. Electronic collection of PROs may facilitate PRO use given these contexts. The second type is use of aggregated PRO data at point of care, including public reporting of PROs to inform decisions at point of care and improve quality of care, and use of PROs for treatment decisions. The third type is use of aggregated PRO data by organizations, including publicly available PRO data to compare centers. In single-payer systems, regular collection of PROs by dialysis centers can be achieved through economic incentives. Both the second and third types of PRO use include pressures that may trigger quality improvement processes. Conclusion: The current state of the evidence is primarily theoretical. There is pressing need for empirical research to improve the evidence-base of PRO use at individual and aggregated levels of nephrology care