From MIA to FIFA: The vicious matrix of frailty, inflammation, fluid overload and atherosclerosis in peritoneal dialysis.

ABSTRACT

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co-existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of 'malnutrition-inflammation-atherosclerosis (MIA) syndrome'. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term 'FIFA complex'. In this system, frailty and atherosclerotic disease may be regarded as two patient-oriented outcomes, while inflammation and fluid overload are two inter-connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti-inflammatory strategies that could alleviate atherosclerotic disease and frailty.