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BackgroundHyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells.MethodsIn this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated.ResultsThe results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 μM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death.ConclusionsThese results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.

In chronic kidney disease (CKD), decreased erythropoietin production, low serum active vitamin D levels, and high renin-angiotensin-aldosterone activities had been regarded as major causes of renal anemia. At present, no clinical data are available to elucidate the association between renal anemia and fibroblast growth factor 23 (FGF23) levels in CKD. This study aimed to access whether FGF23 is involved in the pathogenesis of renal anemia.This cross-sectional observational study included 53 stable outpatients with CKD stages 3 and 4. Our primary predictor was serum FGF23 levels and outcome was hemoglobin levels. Measurements contained hemoglobin, FGF23, 25-hydroxyvitamin D, intact parathyroid hormone, plasma renin, serum aldosterone, HbA1C levels, lipid and iron profiles, and serum and urine electrolytes.Mean age of our patients was 66.4 ± 12.8 (SD) years, mean estimated glomerular filtration rate 33.5 ± 13.9 mL/min/1.73 m2, median FGF23 level 200 (25th–75th percentile, 124–303) pg/mL, vitamin D level 19.5 (25th–75th percentile, 14.0–25.9) ng/mL, and hemoglobin level 12.7 (25th–75th percentile, 10.7–13.75) g/dL. Even after adjusting multiple variables, lower hemoglobin levels correlated significantly with FGF23 levels that were higher than the median value (>200 pg/mL). Moreover, after adjusting for aldosterone, but not 25-hydroxyvitamin D, it decreased the association with FGF23 that higher than median level and hemoglobin levels. We also observed a significant decrease of hemoglobin level in the higher FGF23 group who had a diabetes history.High FGF23 levels were observed to be associated with low hemoglobin levels, which may be partially mediated through the effects of serum aldosterone levels in our patients with CKD stages 3 and 4. Furthermore, we also presumed that diabetes itself may have an impact on the loop among FGF23, hemoglobin, and aldosterone levels in these CKD patients.

The anti-oxidant effects of epigallocatechin gallate (EGCG) and alpha lipoic acid (ALA) have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG)-induced TNF-α and IL-6 production in human embryonic kidney (HEK) cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE) mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.

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