Cardiovascular risk biomarkers in CKD: the inflammation link and the road less traveled

Abstract

End-stage renal disease patients suffer a syndrome of accelerated aging characterized by a 10- to 100-fold increase in cardiovascular and all-cause mortality when compared to age-matched controls. No specific therapeutic interventions have been shown to improve this dismal outcome. Inflammation, chronic kidney disease-mineral and bone disorder (CKD-MBD) and other biomarkers predict outcome in observational studies. However, we lack clinical trials that address the role of these biomarkers in risk stratification and therapeutic decision making. Biomarkers may also provide insights into the pathophysiology of disease and identify novel therapeutic targets. Inflammation emerges as a prime potential target for intervention. Thus, CKD-MBD biomarkers, asymmetrical dimethyl arginine and tri-iodothyronine have a link to inflammation. Interleukin-6 (IL-6) is one of the inflammation biomarkers with highest predictive value for outcome in ESRD. Biologicals targeting IL-6 are approved for the treatment of chronic inflammatory conditions such as rheumatoid arthritis. Furthermore, trials are underway to test IL-6 targeting potential to decrease cardiovascular injury in non-CKD patients. In this regard, targeting IL-1 was recently shown to decrease systemic inflammation in hemodialysis patients. The success of these trials will likely influence future studies on biomarker targeting in CKD.

The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood

“…24 Advanced CKD is characterized by increased oxidative stress and low-level systemic inflammation, best assessed by measuring CRP or IL-6. [25][26][27][28] Both uremia itself and hemodialysis sessions may contribute to oxidative stress and inflammation. BPA exposure has been linked to inflammation and cardiovascular disease in humans and BPA induces oxidative stress and inflammation in rodents and cultured cells.29,30-33 Oxidative stress was associated with BPA-induced experimental hypertension.…”

Inflammatory Cytokines as Uremic Toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”

“…Recent attention has focused on toxins that are not readily removed by dialysis procedures, such as protein-bound, gut-derived molecules [3]. In addition, markers of inflammation, like cytokines and adipokines, are associated with the risk of death in CKD patients, and are not efficiently removed by dialysis [4,5]. We now critically review the inflammation/uremic toxin interface and, specifically, cytokines that are considered uremic toxins or uremic retention solutes, with a focus on defining the potential clinical practice consequences.…”

“…IL-1β was the first interleukin described and is an extremely pro-inflammatory molecule, which circulates at very low concentrations in healthy individuals. In humans, excessive IL-1β secretion is known to cause disease and several therapeutic strategies are available to target IL-1β in inflammatory conditions such as rheumatoid arthritis, including the IL-1β receptor antagonist (IL-1ra) anakinra [4]. IL-1ra belongs to the IL-1β superfamily but binds to the IL-1β receptor non-productively in competition with IL-1β.…”

Janus kinase 3 regulates renal 25-hydroxyvitamin D 1α-hydroxylase expression, calcitriol formation, and phosphate metabolism

“…The cross talk between inflammation and phosphate metabolism is particularly relevant in chronic kidney disease [55][56][57] and associated mineral and bone disease. 58,59 Moreover, the therapeutic use of JAK3 inhibitors 60,61 or of interleukin 12 (refs 62-64) may be paralleled by increase in 1,25(OH) 2 D 3 formation and phosphaturia.…”