Abstract |
Introduction: Protein-energy wasting (PEW) is very frequent among patients with
end stage renal disease (ESRD), contributing to their high mortality rate. The levels of
adipokines, adiponectin (ADPN) and leptin are almost three times higher in ESRD
patients in comparison with the general population. Research has shown conflicting
results concerning the association of ADPN and leptin with PEW and mortality.
Aims: In this study, we investigated the prevalence of PEW in hemodialysis (HD) and
peritoneal dialysis (PD) patients and the relation between ADPN and leptin levels
with nutritional and inflammatory markers in ESRD patients and their possible role in
PEW and mortality.
Methods: 74 ESRD patients, forty-seven (26 men and 21 women) on hemodialysis
(HD), and 27 (15 men and 12 women) on peritoneal dialysis (PD), were assessed at
three sequential time points (baseline, 6 and 18 months) for their nutritional and
inflammatory status and were followed-up for the following 50 months for all-cause
mortality. Anthropometric measurements (weight, height, arm, waist and hip
circumferences), body composition (triceps skinfold and bio-impedance analysis) and
biochemical analysis (albumin, pre-albumin, IL-6, CRP, total cholesterol, phosphorus
etc) were assessed for all patients. Serum ADPN and leptin were also measured at
each time point. Patients were stratified in 3 groups according to PEW severity (0, 1-2
and≥3 criteria for PEW). Diagnosis of PEW included body mass index (BMI)<23,
reduction of arm muscle area (AMA) more than 10% below 50th percentile,
percentage of body fat (%BF) below 10% of body weight and serum albumin levels
<3.8gr/dl and pre-albumin <30mgr/dl.
Results: Adiponectin and leptin levels were higher in PD than in HD patients
(p=0.035). The prevalence of PEW (≥3 criteria) was also higher in PD vs. HD patients
(22.2% vs. 8.5% respectively), whereas a higher proportion of well-nourished patients
(none criterion of PEW) was noticed in HD than in PD (21.3% vs. 18.5%
respectively). However, both differences didn’t reach a statistical significance. ADPN
levels were consistently higher in all 5 PEW criteria examined and increased from
lower to higher PEW stratum (p=0.002). Leptin showed the opposite trend, with lower
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levels in malnourished patients (≥3 criteria of PEW) and higher levels in patients with
zero PEW criteria (p=0.042). Alterations of ADPN levels during the observation
period were dependent on PEW (p=0.021) and the mode of dialysis (p=0.002) (after
adjustment for age, dialysis vintage, gender and fat mass index -FMI-). In particular
HD patients with ≥3 criteria of PEW increased adiponectin levels over time, whereas
PD patients with ≥3 criteria decreased adiponectin levels throughout the study. Leptin
alterations over time were not affected by the mode of dialysis or the PEW. In cox
regression and multiple cox proportional hazard models, each 1μg/ml increment of
ADPN levels was associated with 4% (p=0.013) and 9% increase (p=0.003) in
mortality risk respectively. Furthermore, the lowest sex-specific tertile of leptin (<5.1
for men and <14.9ng/ml for women) was associated with higher risk of all-cause
mortality compared with middle and highest tertiles [crude hazard ratio: 2.95 (95%
CI, 1.17–7.50)]. This low leptin-mortality association persisted even after adjustment
for FMI, age, sex, dialysis mode, baseline CVD, serum albumin and CRP.
Conclusions: Our study provides strong evidence that increased ADPN and decreased
leptin are independently associated with poor prognosis and PEW. The way that these
two adipokines differentially impact on PEW and mortality warrants further
investigation.
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