nitrophenols and Kidney-Failure--Chronic

Components of the renin-angiotensin-aldosterone system such as angiotensin II and aldosterone are believed to contribute to the development and progression of cardiovascular tissue and organ injuries. We compared the effects of two calcium channel blockers, efonidipine and amlodipine, on the renin-angiotensin-aldosterone system in patients with end-stage renal diseases on maintenance hemodialysis. Twenty hypertensive patients on chronic hemodialysis were given efonidipine 20-60 mg twice daily and amlodipine 2.5-7.5 mg once daily for 12 weeks each in a random crossover manner. The average blood pressure was comparable between the efonidipine and amlodipine periods (151 + or - 15/77 + or - 8 versus 153 + or - 15/76 + or - 8 mmHg). The pulse rate did not change significantly during the administration periods. Although the plasma renin activity and plasma angiotensin II were not significantly different between the efonidipine and amlodipine periods, plasma aldosterone was significantly lower in the efonidipine period than in the amlodipine period (123 + or - 118 versus 146 + or - 150 pg/mL, P = 0.027). The findings suggest that efonidipine reduces plasma aldosterone levels in patients on maintenance hemodialysis, and this seems to be an additional benefit to the cardiovascular protection by antihypertensive therapy with efonidipine in patients with end-stage renal disease.

Topics: Aged; Aldosterone; Amlodipine; Blood Pressure; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Cross-Over Studies; Dihydropyridines; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nitrophenols; Organophosphorus Compounds; Renal Dialysis; Renin-Angiotensin System

Pharmacokinetics and pharmacodynamics of irinotecan have been reported to be altered in cancer patients with end-stage kidney disease (ESKD). Carboxylesterase (CES) has an important role in metabolism of irinotecan to its active metabolite, SN-38, in human liver. The purpose of the present study was to investigate whether CES activity was altered in ESKD patients.. The present study investigated the effects of uremic serum, uremic toxins, and fatty acids on the hydrolysis of irinotecan and a typical CES substrate, p-nitrophenyl acetate (PNPA), in human liver microsomes. Normal and uremic serum samples were deproteinized by treatment with methanol were used in the present study.. The present study showed that both normal and uremic serum significantly inhibited CES-mediated metabolism of both irinotecan and PNPA. The inhibition by uremic serum was weaker than that by normal serum, suggesting that CES activity may be higher in ESKD patients. Although four uremic toxins did not affect PNPA metabolism, arachidonic acid inhibited it. There was no difference in inhibitory effect of PNPA metabolism between both mixtures of seven fatty acids used at concentrations equivalent to those present in 10% normal or uremic serum. Interestingly, those mixtures had a more pronounced effect than either 10% normal or uremic serum.. The present study showed that the inhibition of CES activity by uremic serum was weaker than that by normal serum, suggesting that an increase in maximum plasma concentration of SN-38 in cancer patients with ESKD can be attributed to an accelerated CES-mediated irinotecan hydrolysis.

Topics: Carboxylesterase; Case-Control Studies; Fatty Acids; Humans; Irinotecan; Kidney Failure, Chronic; Microsomes, Liver; Nitrophenols; Topoisomerase I Inhibitors; Uremia

Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients.. This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis.. There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1 ± 31.6 vs. 164.3 ± 61.5 U/l, p = 0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2 ± 1.7 vs. 3.9 ± 1.1 mm, p = 0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT (r = -0.484, p = 0.0001) and a significant positive correlation between PON-1 activity and HDL-C (r = 0.417, p = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT.. Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.

Topics: Adipose Tissue; Adult; Aryldialkylphosphatase; Biomarkers; Body Mass Index; Cross-Sectional Studies; Echocardiography; Egypt; Female; Humans; Kidney Failure, Chronic; Lipoproteins, LDL; Male; Middle Aged; Nitrophenols; Pericardium; Renal Dialysis; Statistics as Topic

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Aryldialkylphosphatase; Esterases; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nitrophenols; Paraoxon; Peritoneal Dialysis; Phenylacetates; Reference Values; Renal Dialysis

Topics: False Positive Reactions; Hemoglobins, Abnormal; Humans; Kidney Failure, Chronic; Nitrophenols; Phosphoric Acids