Serum C1q- binding adiponectin in maintenance hemodialysis patients

Abstract

BackgroundPatients on maintenance hemodialysis (HD) have much higher levels of adiponectin (Total-APN). Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We recently reported that C1q-APN/Total-APN ratio rather than Total-APN correlated with atherosclerosis in diabetics. However, the characteristics of C1q-APN in HD patients remain unclear. The preset study investigated the characteristics of the adiponectin parameters including C1q-APN and also to clarify the relationship between various serum adiponectin parameters and atherosclerotic cardiovascular diseases (ACVD) in HD patients.MethodsThe single cross-sectional study subjects were 117 Japanese patients (males/females = 61/56) on regular HD. Blood Total-APN, high molecular weight-adiponectin (HMW-APN), C1q-APN and C1q concentrations were measured by enzyme-linked immunosorbent assays. ACVD were defined as stroke, coronary and peripheral artery diseases, thoracic and abdominal aneurysms.ResultsStepwise regression analysis identified high-density lipoprotein-cholesterol (HDL-C) as the only significant and independent determinant of C1q-APN in males, and duration of HD as the only significant and independent determinant of C1q-APN in females. Stepwise regression analysis identified uric acid, low-density lipoprotein-cholesterol and triglyceride as significant and independent determinants of C1q-APN/Total-APN ratio in males, and leukocyte count and HDL-C as significant and independent determinants of C1q-APN/Total-APN ratio in females. Multiple logistic regression analysis identified inorganic phosphorus and C1q-APN or C1q-APN/C1q ratio as significant determinants of ACVD.ConclusionsLow serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients.Trial registrationClinicalTrials.gov: UMIN http://000004318

Correlation of circulating C1q and C1q-binding adiponectin concentrations with aging in males: a preliminary report

“…As one possible mechanism, three major factors are involved in the control of circulating Total-APN levels; gender, body weight and renal function [4,12,13]. The present study found that advanced age is associated with decreased body weight (r=−0.1612, p=0.0003) and reduced renal function (r=−0.2168, p<0.0001, data not shown).…”

The Complement System in Dialysis: A Forgotten Story?

“…Inflammation and coagulation are principally involved in the pathogenesis of cardiovascular disease. Accordingly, complement has been associated to the susceptibility to cardiovascular disease in HD patients ( 26 , 27 , 45 – 47 ). Plasma C3 levels, prior to a HD session, were found to be higher in patients who develop a cardiovascular event (CV-event) than HD patients who remained event-free.…”

“…Whether this effect is mediated via the complement inhibitory capacity of CR1 or via the recently discovered function of CR1 in the binding and clearance of native LDL remains to be elucidated ( 53 ). Another study showed that low serum C1q-adiponectin/C1q ratios were linked to cardiovascular disease in HD patients ( 45 ). The mechanism behind this connection is not understood but it has been demonstrated that adiponectin protects against activation of C1q-induced inflammation ( 54 ).…”

The amount of C1q–adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal–medial layer of blood vessels of coronary artery disease patients

“…One study has demonstrated that recombinant and native human APN binds to purified C1q under physiological conditions [ 17 ]. Recent studies have reported that the C1q–APN protein complex exists in human blood [ 18 , 19 ] and that the serum C1q–APN/total APN ratio may serve as a biomarker of CAD [ 20 ]. However, the clinical significance and physiological function of the C1q–APN complex and the tissue sites of C1q–APN complex deposition are not well known.…”