Paradoxical role for adiponectin in chronic renal diseases? An example of reverse epidemiology

Adiponectin (ADPN) is an adipocyte-derived protein with potential anti-atherogenic properties. In the general population, ADPN serum levels are associated with age and body mass index (BMI), type 2 diabetes and presumably cardiovascular disease. The suspected vascular-protective effects are mediated by several mechanisms such as insulin sensitizing, maintaining endovascular homeostasis and anti-inflammatory properties. Patients with chronic kidney disease (CKD) are subjected to an increased cardiovascular risk. The underlying mechanisms are not yet completely understood although in the last few years numerous studies have linked secondary hyperparathyroidism and inflammation to that risk. It is currently not clear whether, in CKD, ADPN plays the same role as it is thought to do in the general population or if the uremic environment overwhelms the vascular-protective impact of ADPN. Therefore, characterizing ADPN levels and kinetics in CKD and comparing its concentrations with surrogate markers of cardiovascular risk in CKD might contribute to a better understanding of adipocytokine signaling in renal disease. The review summarizes the available literature on ADPN measurement, regulation and therapeutic potential in general population and CKD. In our investigations, ADPN was more than twofold increased in hemodialysis patients compared with the general population. ADPN levels were not associated with age, but with lifetime spent on dialysis (vintage) and BMI. The dialysis procedure had no effect on ADPN. To assess the clinical value of ADPN levels as a potential surrogate of cardiovascular risk in or therapeutic target in CKD, end point-driven studies with special regard to the risk behavior in CKD have to be performed.