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*

Angiotensin II Type 1 Receptor Blockers/adverse effects* ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/adverse effects* ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/etiology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/etiology* ; SARS-CoV-2

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 associations between angiotensin converting enzyme inhibitors (ACEIs) related cough and ACE I/D and bradykinin beta(2) receptor (BDKRB2) C/T polymorphism.

METHODSA case-control study, nested in a 3-year community-based postmarketing surveillance of benazepril in 1 831 Chinese hypertensives was carried out. Three hundred and fifty-one cases having suffered benazepril related cough were identified and genotyped. Genotyped controls were selected through a stratified sampling design by age, sex and kidney function status.

RESULTSThe allele frequencies in cases were I 65.4%, D 34.6% and T 53.0%, C 47.0% and the genotype frequencies were II 42.2%, ID 46.4%, DD 11.4% (ACE) and CC 21.6%, CT 50.9%, TT 27.6% (BDKRB2), respectively. Genotype frequencies were both in Hardy-Weinberg equilibrium. According to stratified analyses by sex, kidney function status and age, no association was found between BDKRB2 C/T polymorphism and cough. For ACE I/D polymorphism, in men with decompensated kidney function, patients with ID or DD genotype having 4.805 times the risk of those with II genotype in developing cough. In women aged 35 to 49 years with normal or compensated kidney function, the OR of DD genotype was 5.128. No associations were detected in other subgroups.

CONCLUSIONIt was suggested that kidney function status and some specific characteristics surrogated by age and sex had modified the effect of ACE I/D variant on cough.

Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; Benzazepines ; adverse effects ; Cough ; chemically induced ; Female ; Humans ; Hypertension ; drug therapy ; genetics ; physiopathology ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics

INTRODUCTIONThe incidence of cough induced by angiotensin-converting enzyme (ACE) inhibitors has been reported to be 5%-20%, with less than half of affected patients requiring discontinuation due to persistent cough. However, the incidence in the local Asian population has not been studied. This study aimed to objectively evaluate the incidence of discontinuation of ACE inhibitors due to cough, in a primary healthcare centre in Singapore.

METHODSWe retrospectively reviewed the medical records, both electronic and written, of patients who attended Tampines Polyclinic to identify those who were newly prescribed ACE inhibitors. The written medical records were analysed to identify patients who discontinued the use of ACE inhibitors and to find out the reasons for discontinuation.

RESULTSA total of 424 patients were identified during the study period. Out of the 424 patients, 129 (30.4%) discontinued the use of ACE inhibitors due to cough. Overall, 90 (21.2%) patients who were initially started on ACE inhibitors were eventually switched to angiotensin receptor blockers (ARBs).

CONCLUSIONIn our cohort, the incidence of discontinuation of ACE inhibitors due to cough is higher than most other studies. The relationship between ethnicity and tolerance of medications should not be underestimated. As there is a high incidence of discontinuation of ACE inhibitors due to cough in the local population, ARBs may be a reasonable substitute as a first-line medication, if clinically indicated.

Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; Cough ; chemically induced ; Female ; Humans ; Incidence ; Male ; Physicians ; Primary Health Care ; organization & administration ; Retrospective Studies ; Singapore ; Time Factors ; Treatment Outcome

BACKGROUNDThere have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.

METHODSThis study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.

RESULTSMedian follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.

CONCLUSIONThe results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Heart Failure ; drug therapy ; Humans ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged

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

BACKGROUNDCoronary stents are widely used in percutaneous coronary intervention (PCI) procedures. We aimed to explore the incidence, predictors and characteristics of stent thrombosis (ST) after coronary stent implantation in routine clinical practice.

METHODSFrom data of 18 063 consecutive patients who underwent successful stent implantation in Shenyang Northern Hospital from 2004 to 2010, we identified patients with definite ST (n = 140) and control patients (n = 280) matched on age, diagnosis, sex, current antiplatelet medication and stent type. The incidence, predictors and characteristics of ST after coronary stent implantation were investigated.

RESULTSThe incidence of angiographically confirmed ST was 0.78% (140/18 063). The time distribution of ST was acute in 43 (30.7%), subacute in 50 (35.7%), and late in 47 (33.6%) patients. Binary Logistic regression analysis identied the angiotensin-converting enzyme inhibitor (ACEI) (odds ratio (OR) = 0.472, 95%CI: 0.276 - 0.807, P = 0.006) and heparin (OR = 0.477, 95%CI: 0.278 - 0.819, P = 0.007) were associated with an reduced risk of cumulative ST. Stent length (OR = 1.042, 95%CI: 1.026 - 1.058, P < 0.001), serum creatinine total (OR = 1.020, 95%CI: 1.004 - 1.035, P = 0.04), cholesterol (OR = 1.267, 95%CI: 1.021 - 1.573, P = 0.032), glucose (OR = 1.086, 95%CI: 1.002 - 1.176, P = 0.044), and platelet aggregation (OR = 1.113, 95%CI: 1.075 - 1.154, P < 0.001) were associated with an increased risk of cumulative ST.

CONCLUSIONST is associated with longer stent length and higher level of total cholesterol, glucose and platelet aggregation.

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Angiotensin-Converting Enzyme Inhibitors ; metabolism ; Coronary Angiography ; Coronary Thrombosis ; epidemiology ; etiology ; metabolism ; Drug-Eluting Stents ; adverse effects ; Female ; Heparin ; metabolism ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; therapy

BACKGROUNDThe role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.

METHODSOne hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.

RESULTSPatients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.

CONCLUSIONSBenazepril has a protective effect on mild to moderate impairment of renal function during coronary angioplasty. It is safe to use benazepril for treatment of patients with mild to moderate impairment of renal function before coronary intervention.

Acute Kidney Injury ; chemically induced ; prevention & control ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Angiotensin-Converting Enzyme Inhibitors ; Benzazepines ; therapeutic use ; Contrast Media ; adverse effects ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; complications