Olmesartan,an angiotensin Ⅱ receptor blocker,is a commonly used antihypertensive drug.Several case reports and cohort studies in recent years have described a severe gastrointestinal adverse event with chronic diarrhea,intestinal malabsorption,and weight loss after the administration of olmesartan.In such cases,the patients recovered after discontinuing olmesartan.This adverse effect is called olmesartan-associated enteropathy(OAE).This article reviews the potential pathogenesis and clinical characteristics of OAE,which broadens the disease spectrum for the differential diagnosis of chronic diarrhea and intestinal malabsorption.
Angiotensin Receptor Antagonists ; Humans ; Imidazoles ; Intestinal Diseases/diagnosis* ; Tetrazoles/adverse effects*

Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.
Angiotensin Receptor Antagonists/adverse effects* ; Angiotensin-Converting Enzyme Inhibitors ; Capsules ; Diabetic Nephropathies/drug therapy* ; Humans ; Renal Insufficiency, Chronic/drug therapy*

The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, P<0.00001; ARBs vs. control: WMD=-0.24, 95% CI=-0.37-0.11, Z=3.58, P=0.0003). The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.
Aged ; Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Female ; Humans ; Hyperkalemia ; chemically induced ; Male ; Middle Aged ; Renal Dialysis

OBJECTIVE: To evaluate the efficacy and safety of combined treatment with angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on diabetic kidney disease. METHODS: Randomized controlled trials (RCTs) were identified from CoChrane library, PubMed, EMbase, CNKI and VIP. Eleven RCTs involving 602 patients were included and analyzed with Rev Man 5.1 software. RESULTS: Compared with ACEI alone, combined treatment with ARB and ACEI was more effective on decreasing 24 h albuminuria, systolic pressure, average 24 h systolic pressure, diastolic pressure, and average 24 h diastolic pressure but with a high level of serum potassium. Compared with ARB alone, combined treatment with ARB and ACEI was more effective on decreasing systolic pressure and diastolic pressure. Compared with ACEI or ARB alone, we didn't get a definite conclusion that whether combined treatment with ARB and ACEI was more effective on decreasing 24 h proteinuria. CONCLUSION Based on this Meta analysis, combined treatment with ARB and ACEI is safer and has positive effect on diabetic kidney disease. However, small sample size and low methodological quality appeared in most of the trials included in this systematic review. Therefore, available evidence is insufficient to recommend a routine clinical application of combined treatment with ARB and ACEI on diabetic kidney disease.
Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVETo investigate the impact of pre-operative uric acid on acute kidney injury (AKI) after cardiac surgery in elderly patients.

METHODSClinical data were collected from 936 elderly patients (age ≥ 60 years) undergoing cardiac surgery with cardiopulmonary bypass in Guangdong General Hospital between January 2005 and May 2011. The baseline serum creatinine was defined as the latest serum creatinine before surgery, and AKI was diagnosed according to RIFLE criteria. Patients were divided into three groups according to the sex-specific cutoff values of serum uric acid tertiles (group A: ≤ 384.65 µmol/L in men, and ≤ 354.00 µmol/L in women; group B:384.66-476.99 µmol/L in men and 354.01-437.96 µmol/L in women; group C: ≥ 477.00 µmol/L in men and ≥ 437.97 µmol/L in women). Multivariate logistic regression analysis was used to analyze the independent risk factors for AKI.

RESULTSAmong 936 elderly patients, 576 cases (61.5%) developed AKI. Mean uric acid concentration was higher in AKI patients than in Non-AKI patients ( (436.6 ± 119.1) µmol/L vs. (398.0 ± 107.2) µmol/L, P < 0.001). The incidence of AKI was 56.1% (175/312) in group A, 56.3% (175/311) in group B, 72.2% (226/313) in group C (P < 0.001). Multiple logistic regression analysis showed that, after adjusted for age, gender, co-morbidities(hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease), previous cardiac surgery, eGFR<60 ml×min(-1) ×1.73 m(-2), heart function ≥ 3 (NYHA), positive urine protein, combination of coronary artery bypass grafting and valvular surgery, cardiopulmonary bypass operation time, aortic cross-clamping time, pre-operative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers and lipid-lowering drugs use, early postoperative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers, diuretics and digoxin use, post-operation central venous pressure, risk of post operative AKI was significantly higher in group C than in group A (OR:1.897, 95%CI: 1.270-2.833, P = 0.002).

CONCLUSIONPre-operative elevated uric acid is an independent risk factor of AKI after cardiac surgery in elderly patients.

Acute Kidney Injury ; etiology ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Female ; Humans ; Incidence ; Kidney Function Tests ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; Uric Acid ; blood

AIMTo observe the effect of angiotensin-converting enzyme inhibitors (ACEI) and aldosterone receptor blockers on cardiac function to explore the mechanism of cardiac function descending and myocardial injury in calcium-overload rats.

METHODSCalcium-overload in rat was induced by administration of Vitamin D3 plus nicotine. To Estimate the extent of calcium-overload by calcium content. Angiotension II and aldosterone levels in the myocardia were measured by radioimmunoassay. Cardiac function (+/- LVdp/dt, LVESP and LVEDP) were measured by Powerlab. The malondialdehyde (MDA) content, activities of lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemistry.

RESULTSCalcium content increased by 3.2-, 5.8 -fold in myocardial and artery, compared with controls. VDN-treated survivors showed lower + LVdp/dt(max) and -LVdp/dt(max) values, by 27% and 34%, respectively (both P < 0.01). Higher LVESP, and LVEDP by 42 % and 32% (P < 0.01); heart rate and mean arterial pressure were not significantly altered (P > 0.05). The lipid peroxidation products MDA and conjugated diene in myocardia were increased 22% (P < 0.01), 68% (P < 0.05) (P < 0.05), respectively. The plasma activity of CPK and LDH was greatly increased by 4.5-and 3.1-fold (P < 0.01), respectively. ACEI and spironolactone obviously relieved degree of calcium-overload and improved cardiac function and myocardial injury(P < 0.01). Calcium content in myocardia and artery was lower 44%, 39% and 57%, 34%. Lower MDA by 20%, 30%, lower conjugated diene by 44%, 35% than calcium-overload group. The plasma activity of CPK and LDH were obviously decreased 28%, 34% and 20%, 27%, compared with calcium-overload group.

CONCLUSIONCalcium-overload could lead to cardiac function descending and myocardial injury in calcium-overload rats by VDN. ACEI and spironolactone could reduce calcium-overload in myocardial and ameliorate cardiac function and decrease myocardial injury.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Calcium ; adverse effects ; Creatine Kinase ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lipid Peroxidation ; Male ; Malondialdehyde ; analysis ; Mineralocorticoid Receptor Antagonists ; Myocardium ; metabolism ; Nicotine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spironolactone ; pharmacology ; Vitamin D ; pharmacology

BACKGROUND/AIMS: Olmesartan, a widely used angiotensin II receptor blocker (ARB), has been linked to sprue-like enteropathy. No cases of olmesartan-associated enteropathy have been reported in Northeast Asia. We investigated the associations between olmesartan and other ARBs and the incidence of enteropathy in Korea. METHODS: Our retrospective cohort study used data from the Korean National Health Insurance Service to identify 108,559 patients (58,186 females) who were initiated on angiotensin converting enzyme inhibitors (ACEis), olmesartan, or other ARBs between January 2005 and December 2012. The incidences of enteropathy were compared among drug groups. Changes in body weight were compared after propensity score matching of patients in the ACEis and olmesartan groups. RESULTS: Among 108,559 patients, 31 patients were diagnosed with enteropathy. The incidences were 0.73, 0.24, and 0.37 per 1,000 persons, in the ACEis, olmesartan, and other ARBs groups, respectively. Adjusted rate ratios for enteropathy were: olmesartan, 0.33 (95% confidential interval [CI], 0.10 to 1.09; p = 0.070) and other ARBs, 0.34 (95% CI, 0.14 to 0.83; p = 0.017) compared to the ACEis group after adjustment for age, sex, income level, and various comorbidities. The post hoc analysis with matched cohorts revealed that the proportion of patients with significant weight loss did not differ between the ACEis and olmesartan groups. CONCLUSIONS: Olmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population. Additional large-scale prospective studies of the relationship between olmesartan and the incidence of enteropathy in the Asian population are needed.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Asia ; Asian Continental Ancestry Group ; Body Weight ; Cohort Studies* ; Comorbidity ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Incidence ; Insurance Claim Review ; Intestinal Diseases ; Korea ; National Health Programs ; Propensity Score ; Prospective Studies ; Receptors, Angiotensin ; Retrospective Studies ; Weight Loss

OBJECTIVETo investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

METHODSForty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days.

RESULTSLVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05).

CONCLUSIONSThe use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; Benzimidazoles ; administration & dosage ; pharmacology ; Breast Neoplasms ; drug therapy ; surgery ; Carbazoles ; administration & dosage ; pharmacology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; adverse effects ; therapeutic use ; Electrocardiography ; drug effects ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Mastectomy, Radical ; Middle Aged ; Propanolamines ; administration & dosage ; pharmacology ; Stroke Volume ; drug effects ; Tetrazoles ; administration & dosage ; pharmacology ; Troponin ; metabolism

OBJECTIVETo explore the effect of peroxisome proliferator-activated receptor-alpha ( PPAR-alpha) agonist fenofibrate on adipokines expression in high-fat diet fed SD rats and its relationship to insulin resistance (IR).

METHODSRats were randomized into three groups (n = 10) : HD group, fed with high-fat diet; HDF group, fed with high fat diet and treated with fenofibrate; and control group, fed with normal diet. Animals were sacrificed after 4-week follow-up. Plasma lipids, fasting plasma insulin, free fatty acids (FFA), and insulin sensitivity were detected. Reverse transcription-polymerase chain reaction was used to semi-quantitatively determine the mRNA expression of adipokines including tumor necrosis factor-alpha (TNF-alpha) , interleukin-6 (IL-6), angiotensinogen (AGT), angiotensin 11 type 1 receptor (AT1R), and adiponectin in brown fat.

RESULTSThe plasma level of FFA, TG, and homeostatic model approach-IR index were (2. 37+/-0. 60) vs (1. 59+/-0. 30) vs (1. 33+/-0. 34 ) mmol/L, (0. 48+/-0. 11) vs (0. 30+/-0. 04) vs (0. 36+/-0. 07) mmol/L, and 12. 30+/-3. 97 vs 5. 03 +/-1. 88 vs 4. 17+/-1. 27 in the HD group, HDF group, and control group after 4 weeks of treatment with fenofibrate, respectively. The mRNA expressions of TNF-alpha and adiponectin were 1. 726+/-1. 408 vs 0. 713+/-0. 711 vs 0. 593+/-0. 382 and 0. 660+/-0. 192 vs 0. 949+/-0. 35 vs 0. 936+/-0. 130 in these three groups, which showed significant difference between HD group and HDF group (P < 0. 05 ) , while no significant difference between HDF group and control group (P > 0. 05). The mRNA expressions of AGT, AT1 R, and IL-6 had no significant difference among these three groups (P > 0. 05 ).

CONCLUSIONPPAR-alpha agonist fenofibrate may reverse high-fat diet induced lipid abnormalities, improve insulin sensitivity, and regulate the mRNA expressions of TNF-alpha and adiponectin in adipose tissues.

Adiponectin ; biosynthesis ; Adipose Tissue ; drug effects ; metabolism ; Angiotensins ; biosynthesis ; Animals ; Dietary Fats ; adverse effects ; Disease Models, Animal ; Fenofibrate ; pharmacology ; Insulin Resistance ; Interleukin-6 ; biosynthesis ; Lipofuscin ; biosynthesis ; Male ; PPAR alpha ; antagonists & inhibitors ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 2 ; biosynthesis ; Tumor Necrosis Factor-alpha ; biosynthesis