Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin.
BACKGROUND
The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD.


METHODS
In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects.


RESULTS
Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype.


CONCLUSIONS
The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.
Stenvinkel
Peter
P
Division of Renal Medicine and Baxter Novum, Department of Clinical Science and Neurogenetics Unit, Karolinska Institutet, Stockholm, Sweden. peter.stenvinkel@klinvet.ki.se
Marchlewska
Alicia
A
Pecoits-Filho
Roberto
R
Heimbürger
Olof
O
Zhang
Zhengzhong
Z
Hoff
Catherine
C
Holmes
Cliff
C
Axelsson
Jonas
J
Arvidsson
Sivonne
S
Schalling
Martin
M
Barany
Peter
P
Lindholm
Bengt
B
Nordfors
Louise
L
D052242:Adiponectin; D000419:Albuminuria / Q000097:blood / Q000235:genetics; D015415:Biomarkers; D001823:Body Composition; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D014644:Genetic Variation; D005919:Glomerular Filtration Rate; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
D052242:Adiponectin; D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008055:Lipids; D011506:Proteins; D005340:Fibrinogen; D002097:C-Reactive Protein