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PloS One 2018Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear.
METHOD
This observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0-4 months, 0-26 months, and 0-38 months. The renal outcome was defined as a decline in eGFR ≥ 40% during the entire study period.
RESULT
The albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR ≥ 40% was increased by 1.690-folds [95% CI 1.110-2.572, P = 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR ≥ 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients.
CONCLUSION
The time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR ≥ 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome.
Topics: Aged; Albuminuria; Angiotensin II Type 2 Receptor Blockers; Area Under Curve; Cohort Studies; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Olmesartan Medoxomil; ROC Curve; Renal Insufficiency, Chronic; Risk Factors
PubMed: 30148871
DOI: 10.1371/journal.pone.0202676 -
Value in Health : the Journal of the... Nov 2014
PubMed: 27201491
DOI: 10.1016/j.jval.2014.08.1479 -
Biomedicine & Pharmacotherapy =... Dec 2023Given the important role of polymyxin B (PB) in the treatment of drug-resistant Gram-negative bacterial infections, the emergence of PB resistance poses a serious threat...
Given the important role of polymyxin B (PB) in the treatment of drug-resistant Gram-negative bacterial infections, the emergence of PB resistance poses a serious threat to public health. Adjuvant development is a supplementary strategy that can compensate for the lack of novel antibiotics by protecting PB. In this study, we found a small molecule named Lyb24 that showed weak antibacterial activity (minimum inhibitory concentration ≥ 10 μg/ml) but potentiated and revitalized the efficacy of PB against Gram-negative pathogens, including mcr-1- and mgrB-deletion-mediated PB-resistant strains. Our results showed that Lyb24 inhibits the translational levels of genes associated with the modification of lipid A. In addition, Lyb24 increases the permeability, disrupts the integrity and induces the depolarization of the membrane. We further found that both Lyb24 and PB could directly bind to AzoR and inhibit its activity. Structural analysis showed that Lyb24 binds to the isoalloxazine ring of flavin mononucleotide (FMN) through pi-pi stacking and loop η4 of AzoR. A pneumonia model was used to confirm that the activity against clinical PB-resistant Klebsiella pneumoniae was enhanced due to Lyb24 on PB. In conclusion, we provide a potential therapeutic regimen by combining Lyb24 and PB to treat Gram-negative-resistant bacterial infections. Our findings not only explain the synergistic effect of Lyb24, but also expand our knowledge on the mechanism of action of PB.
Topics: Polymyxin B; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Anti-Bacterial Agents; Klebsiella pneumoniae; Microbial Sensitivity Tests
PubMed: 37949698
DOI: 10.1016/j.biopha.2023.115856 -
Advanced Pharmaceutical Bulletin Jul 2020The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of...
The present work endeavors to report a systematic approach of developing the lipidic self-nanoemulsifying formulation of olmesartan medoxomil (OMT) on the principles of Quality by Design (QbD). For preparing the self-nanoemulsifying formulation, a mixture of oil, surfactant and cosurfactant were used as vehicles. The excipients were selected after screening by solubility as well as pseudoternary phase titration studies. Mixture design was adopted for systematic optimization of the composition of nanolipidic formulations, which were evaluated for smaller globule size, stable zeta potential and lower values of polydispersity index. The optimized liquid self-nanoemulsifying formulation was identified using numerical and graphical optimization techniques, followed by validation of the experimental model. Solidification of self-nanoemulsifying formulation was carried out using porous carriers, and then optimized on the basis of oil adsorption potential, powder flow property and drug release performance. Pharmacokinetic study was performed in male Wistar rats for evaluating the drug absorption parameters. All the experimental data obtained were subjected to statistical analysis using oneway ANOVA followed by post hoc analysis using Student's t test. The optimized liquid self-nanoemulsifying formulation showed globule size <100 nm, emulsification efficiency <5 minutes and drug release >85% within in 30 minutes. Further, the solid SNEDDS formulation was effectively formulated using Neusilin US2 with maximum oil adsorption capacity and good micromeritic properties. Pharmacokinetic evaluation indicated 4 to 5-folds increase ( <0.05) in the values of C, AUC, and reduction in T from the nanoformulations vis-à-vis the marketed formulation. Overall, the developed nanolipidic formulation of olmesartan indicated superior efficacy in augmenting the drug dissolution and absorption performance.
PubMed: 32665896
DOI: 10.34172/apb.2020.046 -
Case Reports in Pediatrics 2018Fetal angiotensin II receptor antagonist exposure is associated with major complications and even death when administered during pregnancy. Neonates frequently require...
Fetal angiotensin II receptor antagonist exposure is associated with major complications and even death when administered during pregnancy. Neonates frequently require intensive care treatment, and mortality is high. Despite this well-known risk potential, a considerable number of women still receive angiotensin II receptor antagonists during pregnancy to treat arterial hypertension. Although clinical symptoms in the neonatal period are well described, few reports address long-term follow-up after fetal exposure to angiotensin II receptor antagonists. We here report on a patient who was unwittingly exposed to olmesartan medoxomil during pregnancy. After birth, the neonate presented with mild clinical symptoms, mainly affecting the kidneys. However, neurodevelopmental follow-up revealed a delay in motor development with muscular hypotonia and failure to thrive at age 2 years. This case highlights the fact that, despite not causing neurological symptoms in the neonatal period, fetal angiotensin II receptor antagonist exposure during pregnancy might lead to neurodevelopmental impairment in later life.
PubMed: 29527375
DOI: 10.1155/2018/5412138 -
BMC Pharmacology & Toxicology Jan 2020Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the...
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the urinary excretion of excess glucose. SGLT2 inhibitors have been reported to suppress the complications of diabetes and reduce overall mortality. However, little is known about the types of symptoms that may occur in response to an overdose of an SGLT2 inhibitor. Here, we describe a case of intoxication caused by an overdose of an SGLT2 inhibitor.
CASE PRESENTATION
An otherwise physically healthy adult woman ingested an overdose of ipragliflozin, an SGLT2 inhibitor, and a polypill of olmesartan medoxomil, and azelnidipine in a suicide attempt. Although her blood ipragliflozin concentration was very high (9516.3 ng/mL) upon hospital arrival, her initial blood glucose level was normal, and she did not exhibit symptoms such as hypoglycemia or polyuria. Moderate renal dysfunction associated with an estimated glomerular filtration rate of 42.3 mL/min/1.73 m was observed. Thirty-six hours after ingestion, her blood ipragliflozin concentration decreased to a level equivalent to that observed after a therapeutic dose and her renal function improved almost simultaneously. After improvement in her renal function, the osmotic diuretic effect of the drug progressed. Her blood glucose level declined slightly but was in the normal range due to glucose administration. During the clinical course, fatal hypoglycemia was not observed.
CONCLUSIONS
Our case showed that an overdose of an SGLT2 inhibitor caused toxic effects on renal function, but severe hypoglycemia was not observed. Additional cases of intoxication from SGLT2 inhibitors alone would be helpful to clarify the mechanism of intoxication.
Topics: Adult; Drug Overdose; Female; Glucosides; Humans; Hypotension; Kidney; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes
PubMed: 31918741
DOI: 10.1186/s40360-019-0381-z -
Journal of Clinical Hypertension... Mar 2017In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule... (Randomized Controlled Trial)
Randomized Controlled Trial
The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure.
In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d.
Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Diastole; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles; Treatment Outcome
PubMed: 27558280
DOI: 10.1111/jch.12895 -
Journal of Clinical Hypertension... Apr 2018
Topics: Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Olmesartan Medoxomil; Oxadiazoles; Renal Insufficiency, Chronic; Tetrazoles
PubMed: 29504233
DOI: 10.1111/jch.13233 -
Journal of Clinical Hypertension... Jan 2018
Topics: Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Humans; Hydrochlorothiazide; Hypertension; Olmesartan Medoxomil; Oxadiazoles
PubMed: 29067786
DOI: 10.1111/jch.13125 -
PloS One 2015Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and... (Randomized Controlled Trial)
Randomized Controlled Trial
The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial.
Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.
Topics: Albuminuria; Angiotensin Receptor Antagonists; Case-Control Studies; Erythropoietin; Female; Hemoglobins; Humans; Hypertension; Male; Middle Aged; Olmesartan Medoxomil; Receptors, Angiotensin; Renin-Angiotensin System; Treatment Outcome
PubMed: 26098847
DOI: 10.1371/journal.pone.0128632