The role of serum magnesium and calcium on the association between adiponectin levels and all-cause mortality in end-stage renal disease patients.

BACKGROUND: Adiponectin (ADPN) is the most abundant adipocyte-specific cytokine that plays an important role in energy homeostasis by regulating lipid and glucose metabolism. Studies of the impact of ADPN on clinical outcomes have yielded contradictory results so far. Here, we examined the association of ADPN with serum magnesium (s-Mg) and calcium (s-Ca) levels and explored the possibility whether these two factors could modify the relationship between ADPN and all-cause mortality in patients with end-stage renal disease. METHODOLOGY/PRINCIPAL FINDINGS: After baseline assessment, 47 hemodialysis and 27 peritoneal dialysis patients were followed- up for a median period of 50 months. S-Mg and s-Ca levels emerged as positive and negative predictors of ADPN levels, respectively. During the follow-up period 18 deaths occurred. There was a significant 4% increased risk for all-cause mortality for each 1-µg/ml increment of ADPN (crude HR, 1.04; 95% CI, 1.01-1.07), even after adjustment for s-Mg and s-Ca levels, dialysis mode, age, albumin and C-reactive protein. Cox analysis stratified by s-Mg levels (below and above the median value of 2.45 mg/dl) and s-Ca levels (below and above the median value of 9.3 mg/dl), revealed ADPN as an independent predictor of total mortality only in the low s-Mg and high s-Ca groups. Furthermore, low s-Mg and high s-Ca levels were independently associated with malnutrition, inflammation, arterial stiffening and risk of death. CONCLUSIONS/SIGNIFICANCE: The predictive value of ADPN in all-cause mortality in end-stage renal disease patients appears to be critically dependent on s-Mg and s-Ca levels. Conversely, s-Mg and s-Ca may impact on clinical outcomes by directly modifying the ADPN's bioactivity

Association of adiponectin with all-cause mortality stratified by serum Mg and dialysate calcium.

*<p>adjusted for age, C- reactive protein and albumin.</p><p>E/P, events/patients.</p

Characteristics of the patients classified into low- and high- adiponectin levels.

<p>Values expressed as mean ± SD or median (interquartile range).</p><p>CVD, cardiovascular disease; HD, hemodialysis; PD, peritoneal dialysis; RRT, renal replacement therapy; ACEI’s, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CCB, calcium channel blockers.</p>*<p>Partial coefficients of correlations between adiponectin and baseline characteristics (anthropometric, inflammatory and nutritional) after correction for fat mass index.</p

Crude and adjusted hazard ratios of serum adiponectin (per 1 µg/ml) for prediction of all-cause mortality in 74 prevalent ESRD patients.

<p>Data adjustment for variables related to adiponectin (model 2), as well as for traditional risk factors (model 3), did not modify the relationship between adiponectin levels and all-cause mortality.</p><p>ADPN, adiponectin; PD, peritoneal dialysis; HD, hemodialysis.</p

Kaplan-Meier analyses comparing the lowest sex-specific tertile of adiponecting (<14 for men and <18 µg/ml for women) to the higher (middle and highest) tertiles.

<p>The number of patients at risk are given below the plot.</p

Multiple regression analysis for assessing the predictors of serum adiponectin levels.

<p>Std beta, standardized regression coefficients; r, correlation coefficient;</p><p>BMI, body mass index;</p