Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5/6 Nephrectomy.
To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC.
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.
Patients with diabetes with end-stage renal failure have elevated serum angiotensin-converting enzyme (ACE) activity compared with their nonuremic counterparts.
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).
Compared with controls, phosphorylation of the adiponectin downstream effector adenosine monophosphate-activated protein kinase (AMPK) was higher in ESRD while acetyl-CoA carboxylase phosphorylation (ACC-P) and carnitine palmitoyl transferase-1 (CPT-1) levels were lower.
In both type 1 and type 2 diabetes (T2D) patients with DKD, elevated adiponectin serum levels have been observed, and adiponectin serum level is a prognostic factor of end-stage renal disease.
In conclusion, higher adiponectin levels are associated with a higher risk of ESRD independent of conventional risk factors, BMI, and metabolic syndrome components.
MCP-1 expression in endothelial cells treated with uremic serum from ESRD patients with hypertension only was significantly increased compared with its expression in other cohorts.
Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001).
Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group.
Osthole treatment significantly attenuated the protein expression of transforming growth factor‑β1 (TGF‑β1), reduced monocyte chemoattractant protein‑1 activity and increased the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) ratio in CRF rats.
The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.
Decreased expression of transforming growth factor-β1 and α-smooth muscle actin contributes to the protection of lotensin against chronic renal failure in rats.
Although plasma levels of adiponectin, a recently discovered anti-inflammatory and antiatherogenic adipocytokine, are markedly elevated in ESRD, gene expression of adiponectin (ApM1) has not been analyzed in ESRD patients.