The effects of early glycosylation products (Amadori Products, AP) were investigated in male Munich-Wistar rats to establish whether AP play a role in the pathogenesis of glomerular hyperfiltration of early diabetic nephropathy. To mimic such a condition, normal rats were transfused with blood containing in vitro glycated serum (Group GLYC) to achieve plasma levels of Amadori products similar to those measured in rats with streptozotocin-induced diabetes. Rats transfused with normal blood were used as control (Group CON). Glomerular hemodynamics was evaluated in basal condition (B) and during acute hyperglycemia (HG). Blood transfusion did not alter basal hemodynamics. In Group CON, HG determined a rise of single nephron GFR (41.4 +/- 3.2 vs. 32.1 +/- 1.8 nl/min, P less than 0.005), secondary to the increase of afferent effective filtration pressure (EFPa, +19% vs. B, P less than 0.01). Rats of Group GLYC, in B, had values of SNGFR higher than those of Group CON B (46.8 +/- 3 nl/min, P less than 0.05, ANOVA). This increase was mediated by a significant reduction of glomerular afferent arteriole (Ra, -38% vs. Group CON B, P less than 0.05), a rise in hydrostatic gradient pressure in glomerular capillaries (delta P, +17%, P less than 0.05) and of EFPa (+31%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to gain further insight into the greater susceptibility to acute ischemic renal failure (ARF, 30 min of renal arteries clamping) of old rats (O, 18 months) as against young rats (Y, 3 months). All the rats ate a hypoproteic diet (14% of casein) to avoid age-related glomerulosclerosis in O. Basal renal dynamics was similar in O and Y (Groups CON). One day after ARF, the decrease in GFR was more severe in O than in Y (-82% and -57% vs. respective CON, P < 0.05), due to a greater rise of RVR in O (+258%) than in Y (+104%). The histological renal damage after ischemia was comparable in the two groups with ARF. Five days after ARF, the recovery of renal function was characterized by a slower rise of GFR in O than in Y. In two further groups, two different scavengers of oxygen-free radicals, dimethylthiourea (DMTU) and superoxide dismutase (SOD), were administered at the time of arterial occlusion. DMTU had protective effects in Y but not in O (delta GFR was -28% and -72%, respectively); in contrast, SOD was more effective in O (delta GFR = -58%) than in Y rats (delta GFR = -40%). To test the hypothesis that such a difference was related to the capacity of SOD to increase the levels of nitric oxide (NO), four more groups of Y and O rats were pretreated with L-arginine (ARG), precursor of NO, in tap water (1.5%). No difference in renal dynamics was detected in basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Anemia is one of the most frequent and earliest complications of chronic kidney disease (CKD), which impacts a patient’s quality of life and increases the risk of adverse clinical outcomes. Patients’ inflammatory status is strictly related to the occurrence of functional iron deficiency anemia (IDA) because this causes an increase in hepcidin levels with the consequent inhibition of iron absorption and release from cellular stores into blood circulation. The aim of this study was to evaluate the use of the new oral formulation based on ferric sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate, and selenomethionine (Ferachel Forte®) in patients with moderate CKD and functional IDA, analyzing the inflammatory status in addition to iron blood parameters, in comparison with oral ferrous sulfate and liposomal iron therapies. Sixty-two elderly patients were randomly allocated to one of the following oral treatments for 6 months: ferrous sulfate (Group 1; N = 20), ferric sodium EDTA in combination (Group 2; N = 22), and ferric liposomal formulation (Group 3; N = 20). The evaluated parameters included iron profile parameters of hemoglobin (Hb), sideremia, ferritin, transferrin saturation, C-reactive protein (CRP), and hepcidin. The results showed that in Group 1, there were no improvements. In Group 2, there were statistically significant (p < 0.001) improvements in all evaluated parameters. Finally, in Group 3, there were significant improvements in all evaluated parameters except for hepcidin, which was less than that of Group 2 patients. In conclusion, the findings showed the superior efficacy of the formulation based on ferric sodium EDTA over the other oral iron sources, and that this formulation can contribute to reducing the systemic inflammatory status in patients with CKD.
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