Advanced oxidation protein products and advanced glycation end products in children and adolescents with chronic renal insufficiency.

OBJECTIVE: Advanced oxidation protein products (AOPPs) represent dityrosine-containing cross-linked protein modifications formed mainly via myeloperoxidase reaction, supposed to accelerate the uremia-associated atherogenesis and renal fibrosis. DESIGN, SUBJECTS, AND MAIN OUTCOME MEASURES: In a cross-sectional study, we investigated the accumulation of AOPPs and advanced glycation end product (AGE)-specific fluorescence corrected for albumin in children and adolescents with chronic renal failure (CRF, n = 42), end-stage renal disease (ESRD, n = 12), kidney transplanted patients (Tx, n = 16), and age-matched healthy controls (n = 38). RESULTS: AOPP levels were 2.4-fold higher in the CRF and ESRD patients, and 1.6-fold higher in the transplanted subjects when compared with the controls (P < .001). In comparison with healthy controls, AGE levels rose 2-fold in the CRF, 7-fold in the ESRD, and 5-fold in the kidney transplanted children and adolescents, (P < .001). Patients with cardiovascular affliction presented with higher AGE levels than those without diagnosed cardiovascular disease (P < .02). In patients with stabilized renal function, AOPP and AGE levels did not change significantly during 12 months. CONCLUSION: Pattern of accumulation of AOPP and AGE in children and adolescents with chronic renal disease differs. Accelerated rise in AOPP levels in some children and adolescents in predialysis stage of chronic renal insufficiency, inadequate to deterioration of renal function, might require further attention.

The peroxisome proliferator-activated receptor-α agonist, BAY PP1, attenuates renal fibrosis in rats.

Recent studies have shown renoprotective effects of the peroxisome proliferator-activated receptor-α (PPAR-α), but its role in kidney fibrosis is unknown. In order to gain insight into this, we examined the effect of a novel PPAR-α agonist, BAY PP1, in two rat models of renal fibrosis: unilateral ureteral obstruction and the 5/6 nephrectomy. In healthy animals, PPAR-α was expressed in tubular but not in interstitial cells. Upon induction of fibrosis, PPAR-α was significantly downregulated, and treatment with BAY PP1 significantly restored its expression. During ureteral obstruction, treatment with BAY PP1 significantly reduced tubulointerstitial fibrosis, proliferation of interstitial fibroblasts, and TGF-ß(1) expression. Treatment with a less potent PPAR-α agonist, fenofibrate, had no effects. Treatment with BAY PP1, initiated in established disease in the 5/6 nephrectomy, halted the decline of renal function and significantly ameliorated renal fibrosis. In vitro, BAY PP1 had no direct effect on renal fibroblasts but reduced collagen, fibronectin, and TGF-ß(1) expression in tubular cells. Conditioned media of BAY PP1-treated tubular cells reduced fibroblast proliferation. Thus, renal fibrosis is characterized by a reduction of PPAR-α expression, and treatment with BAY PP1 restores PPAR-α expression and ameliorates renal fibrosis by modulating the cross-talk between tubular cells and fibroblasts. Hence, potent PPAR-α agonists might be useful in the treatment of renal fibrosis.

Association of sVAP-1, sRAGE, and CML with lactation-induced insulin sensitivity in young non-diabetic healthy women.

BACKGROUND: In comparison with non-lactating women breast-feeding mothers display higher insulin sensitivity. Recent data suggest that advanced glycation end products, soluble receptor for advanced glycation end products (sRAGE) and soluble vascular adhesion protein-1 (sVAP-1) may play a role in insulin resistance even in healthy subjects. AIM: We studied whether breast-feeding induced insulin sensitivity associates with changes in concentrations of circulating sVAP-1, sRAGE and N(ε)-(carboxymethyl)lysine (CML) - chemically defined advanced glycation end product and RAGE ligand. METHODS: In 74 lactating non-diabetic mothers, 45 weaned non-diabetic mothers and 50 age-matched non-parous women insulin sensitivity was assessed using Quantitative insulin-sensitivity check index (QUICKI). sVAP-1, sRAGE and CML levels were determined. RESULTS: Lactating mothers were more insulin sensitive than their weaned and non-parous counterparts. Lactating mothers displayed the highest concentrations of sRAGE, and higher sVAP-1 levels if compared to weaned mothers. Both groups of mothers presented with lower CML levels than the non-parous women. CONCLUSION: Lactation-induced insulin sensitivity is associated with higher sVAP-1 and a tendency towards higher sRAGE levels. Lactation-associated rise in sVAP-1 may promote effective glucose utilization in the mother. Lactation-induced insulin sensitivity vanishes shortly after weaning. In young healthy women CML levels are of no clinical relevance to insulin sensitivity.

Plasma concentration and urinary excretion of N epsilon-(carboxymethyl)lysine in breast milk- and formula-fed infants.

Industrial processing of infant formulas (IFs) induces the formation of Maillard products, namely N epsilon-(carboxymethyl)lysine (CML). CML content is expected to be several times higher in IFs than in fresh human breast milk. To elucidate whether CML is absorbed from IFs into the bloodstream, CML concentration in the plasma and urine were analyzed in 6-month-old infants (34 breast fed and 25 fed exclusively with IFs) and in 56 samples of human breast milk and 16 commercial IFs. We found that IFs contain higher amounts of CML compared to mother's milk (median: 70-fold; range: 28- to 389-fold), and CML content was higher in hydrolyzed IFs than in nonhydrolyzed IFs (P < 0.03). Plasma CML levels were 46% higher (P < 0.01) and urinary excretion of CML was 60-fold higher (P < 0.001) in the formula-fed infants than in the breast-fed group. Infants fed with hydrolyzed IFs displayed significantly higher plasma CML levels than those on nonhydrolyzed formulations. We conclude that CML from IFs is absorbed into the circulatory system and is rapidly excreted in the urine.