End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

Abstract

Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted.

Ankle‐brachial index, arterial stiffness, and biomarkers in the prediction of mortality and outcomes in patients with end‐stage kidney disease

“…Abnormal ABI has been shown to be well correlated with systemic disease burden of atherosclerosis, which is a strong predictor of MACE . On the other hand, accumulating evidence demonstrated that an elevation of cTn is specific to myocardial damage and hs‐CRP reflects systematic atherosclerotic burden and activity even in ESKD patients . As multiple organ disorder causes markedly higher systemic adverse events, these observations suggest that biomarker approach complements the risk assessment that cannot be identified by ABI alone, and their combination could provide better risk stratification of ESKD patients treated with HD.…”

Malnutrition Risk in Hemodialysis Patients in Israel: Results of the Status of Nutrition In Hemodialysis Patients Survey Study

“…CRP, an acute phase reactant, is known to be directly associated with malnutrition in HD patients [31]. Persistent low-grade inflammation is common among patients with chronic renal disease [32]. Moreover, malnutrition in CKD patients is associated with a proinflammatory state [33].…”

The Relationship of Residual Renal Function with Cardiovascular Morbidity in Hemodialysis Patients and the Potential Role of Monocyte Chemoattractant Protein-1

“…Vice versa, the liquid imbalance in these patients, defined by both sodium retention and loss of RRF, promotes endothelial dysfunction and progression of inflammation/ oxidative stress, contributing to an increased MCP-1 production resulting in more adverse effects on the cardiovascular system. Indeed, fluid overload is included in promoting the inflammation factors [11].…”

“…Atherosclerosis and cardiovascular disease in this patient population are mainly affected by nontraditional risk factors, including persistent low-grade inflammation, metabolic acidosis, volume overload, and comorbidities. The causes of inflammation are multifactorial and include imbalance between increased production and decreased removal of pro-inflammatory cytokines, oxidative stress, factors linked to dialysis treatment, and chronic and recurrent infections related to dialysis access [11].…”