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Frontiers in Medicine 2022Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed...
BACKGROUND
Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed to be an important adjuvant therapy for hypertensive nephropathy.
OBJECTIVE
To evaluate the efficacy of HQI combined with antihypertensive drugs in the treatment of hypertensive nephropathy.
MATERIALS AND METHODS
We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Knowledge Service Platform (WanfangData), Chinese Biomedical Database (CBM), EMBASE, PubMed and Cochrane Library from their inception to April 23st, 2021. All studies were independently screened by two auditors according to the inclusion and exclusion criteria. Randomized controlled trials comparing HQI in combination with antihypertensive drugs vs. antihypertensive drugs alone were extracted.
RESULTS
The meta-analysis included 15 studies involving 1,483 participants.The effect of HQI combined with antihypertensive drugs is better than that of antihypertensive drugs alone in regulating hypertensive nephropathy for reducing 24-h urinary total protein (24 h UTP) [WMD=-0.29, 95% CI (-0.40, -0.18), = 0.000], microalbuminuria (mALB) [WMD = -17.04, 95% CI (-23.14, -10.94), = 0.000], serum creatinine (SCr) [WMD = -40.39, 95% CI (-70.39, -10.39), = 0.008], systolic blood pressure (SBP) [WMD = -9.50, 95% CI (-14.64, -4.37), = 0.000], diastolic blood pressure (DBP) [WMD = -4.588, 95% CI (-6.036, -3.140), = 0.000], cystatin-C (Cys-c) [WMD = -0.854, 95% CI (-0.99, -0.72), = 0.000], blood urea nitrogen (BUN) [WMD = -4.155, 95% CI (-6.152, -2.157), = 0.000].
CONCLUSION
The combination of HQI and antihypertensive drugs is more efficient in improving the related indexes of patients with hypertensive nephropathy than using antihypertensive drugs alone, and a moderate dose of HQI (no more than 30 mL) may benefit more. However, the quality of the methodology is low and the number of samples is small, the results need to be confirmed by more stringent randomized controlled trials.
PubMed: 35547210
DOI: 10.3389/fmed.2022.838256 -
Oxidative Medicine and Cellular... 2022Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic nephropathy (DN), one of the commonest diabetic microangiopathies, with artemisinins. Here, we aimed to evaluate preclinical evidence for the efficacy and possible mechanisms of artemisinins in reducing diabetic renal injury.
METHODS
We conducted an electronic literature search in fourteen databases from their inception to November 2021. All animal studies assessing the efficacy and safety of artemisinins in DN were included, regardless of publication or language. Overall, 178 articles were screened according to predefined inclusion and exclusion criteria. Finally, 18 eligible articles were included in this systematic review. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool was used to assess the risk of bias in the included studies. The primary outcomes were kidney function, proteinuria, and renal pathology. Secondary endpoints included changes in fasting plasma glucose (FPG) levels, body weight, and relevant mechanisms.
RESULTS
Of the 18 included articles involving 418 animal models of DN, 1, 2, 6, and 9 used dihydroartemisinin, artemether, artesunate, and artemisinin, respectively. Overall, artemisinins reduced indicators of renal function, including blood urea nitrogen ( < 0.00001), serum creatinine ( < 0.00001), and kidney index ( = 0.0001) compared with control group treatment. Measurements of proteinuria ( < 0.00001), microalbuminuria ( < 0.05), and protein excretion ( = 0.0002) suggested that treatment with artemisinins reduced protein loss in animals with DN. Artemisinins may lower blood glucose levels ( = 0.01), but there is a risk of weight gain ( < 0.00001). Possible mechanisms of action of artemisinins include delaying renal fibrosis, reducing oxidative stress, and exerting antiapoptotic and anti-inflammatory effects.
CONCLUSION
Available evidence suggests that artemisinins may be protective against renal injury secondary to diabetes in preclinical studies; however, high-quality and long-term trials are needed to reliably determine the balance of benefits and harms.
Topics: Animals; Artemisinins; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Male; Models, Animal; Proteinuria
PubMed: 35528521
DOI: 10.1155/2022/5401760 -
The Cochrane Database of Systematic... Dec 2021Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of... (Review)
Review
BACKGROUND
Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013 and 2015.
OBJECTIVES
To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS
The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 18 October 2021. We also searched clinical trial registries. Date of the most recent search: 22 August 2021.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS
Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS
Seven studies were identified through the searches. Six studies were excluded. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. Overall, the certainty of the evidence provided in this review was very low, since most risk of bias domains were judged to have either an unclear or a high risk of bias. Because of this, we are uncertain whether captopril makes any difference, in total urinary albumin excretion (at six months) as compared to the placebo group, although it yielded a mean difference of -49.00 (95% confidence interval (CI) -124.10 to 26.10) or in the absolute change score, although it yielded a mean difference of -63.00 (95% CI -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean (standard deviation) of 45 (23) mg/day and the placebo group was noted to increase by 18 (45) mg/day. Serum creatinine and potassium levels were reported constant throughout the study (very low-certainty evidence). The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, we judged the certainty of the evidence to be very low. The included study selectively reported its results, was not powered to detect a group difference, should it exist, and otherwise did not offer enough information to allow us to judge the bias inherent in the study. Indirectness (in relation to the limited age and type of population included) and imprecision (wide confidence intervals around the effect estimate) were observed. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study. Overall, we judged the certainty of this evidence to be very low.
Topics: Albuminuria; Anemia, Sickle Cell; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Humans; Proteinuria; Randomized Controlled Trials as Topic
PubMed: 34932828
DOI: 10.1002/14651858.CD009191.pub4 -
Frontiers in Pharmacology 2021We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on... (Review)
Review
We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, = 0.01; = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, = 0.03; = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, = 0.003; = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, = 0.01; = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, < 0.00001; = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, = 0.003; = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF ( = 0.80 for interaction). Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
PubMed: 34867310
DOI: 10.3389/fphar.2021.604017 -
Ultrasound (Leeds, England) Aug 2021The diagnosis of diabetic kidney disease can be delayed by limitations of primary biomarkers, which are microalbuminuria and estimated glomerular filtration rate. A... (Review)
Review
The diagnosis of diabetic kidney disease can be delayed by limitations of primary biomarkers, which are microalbuminuria and estimated glomerular filtration rate. A number of Doppler ultrasound studies have associated an increase in intrarenal vascular resistance with the disease, which makes ultrasound a potential adjunct tool for early diagnosis. However, there is inadequate evidence to establish the effectiveness of including Doppler ultrasound in the diagnostic process. This systematic review was therefore conducted to determine the value of using Doppler ultrasound in early detection of diabetic kidney disease. Electronic literature searches were carried out in PubMed, CINAHL, Web of Science and EMBASE. All published prospective studies with records of intrarenal Doppler ultrasound, microalbuminuria and estimated glomerular filtration rate were obtained, and their relationship as parameters for diabetic kidney disease assessed. The meta-analysis of Doppler ultrasound versus albuminuria shows insignificant statistical difference between high resistive index of ≥ 0.7 and albuminuria, with the resistive index being the favoured parameter on the forest plot, making Doppler ultrasound highly comparable with albuminuria for the detection of diabetic kidney disease. Again, there was a significant statistical difference between high intrarenal resistive index of ≥ 0.7 and low estimated glomerular filtration rate of 60 mL/min/1.73 m, with the resistive index being the favoured parameter on the forest plot, making Doppler ultrasound a superior parameter compared with estimated glomerular filtration rate for early detection of diabetic kidney disease.
PubMed: 34567226
DOI: 10.1177/1742271X20977051 -
Frontiers in Cardiovascular Medicine 2021Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse...
Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse outcomes. To date, no study has synthesized evidence on its role as a prognostic indicator. Thus, the current study aimed to quantitatively assess the prognostic utility of albuminuria as well as dipstick proteinuria in predicting mortality in heart failure patients. PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched up to October 10, 2020. All studies reporting multivariable-adjusted hazard ratios (HR) for albuminuria or dipstick proteinuria for mortality and/or hospitalization in heart failure patients were included. Eleven studies were included. Seven assessed albuminuria and five assessed dipstick proteinuria. Our analysis revealed a statistically significant increased risk of all-cause mortality with microalbuminuria (HR: 1.54; 95% CI, 1.23-1.93; = 79%; = 0.0002) and macroalbuminuria (HR: 1.76; 95% CI, 1.21-2.56; = 88%; = 0.003) in heart failure patients. The risk of all-cause mortality and hospitalization was also significantly increased with macroalbuminuria. Microalbuminuria was associated with significantly increased cardiovascular mortality and combined cardiovascular mortality and hospitalization. Positive dipstick test for proteinuria was significantly associated with mortality in heart failure (HR: 1.54; 95% CI, 1.28-1.84; = 67%; < 0.00001). Both microalbuminuria and macroalbuminuria are predictors of mortality in patients with heart failure. Dipstick proteinuria may be used as a rapid screening test to predict mortality in these patients.
PubMed: 34055938
DOI: 10.3389/fcvm.2021.665831 -
Endocrinology and Metabolism (Seoul,... Apr 2021To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with... (Meta-Analysis)
Meta-Analysis
Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.
BACKGROUND
To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes.
METHODS
We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes.
RESULTS
Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors.
CONCLUSION
SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.
Topics: Bayes Theorem; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Glucose; Humans; Hypoglycemic Agents; Kidney; Network Meta-Analysis; Sodium
PubMed: 33789035
DOI: 10.3803/EnM.2020.912 -
Diabetology & Metabolic Syndrome Jan 2021Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according...
BACKGROUND
Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.
METHODS
Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case-control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese. Finally, twenty-five studies were included in this meta-analysis.
RESULTS
Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD = 1.62, 95% CI 1.08 to 2.25, P = 0.000; GDM: SMD = 2.85, 95% CI 1.01 to 4.70, P = 0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD = 1.58, 95% CI 0.59 to 2.56, P = 0.002; microalbuminuria: SMD = 2.57, 95% CI 0.92 to 4.22, P = 0.002; macroalbuminuria: SMD = 2.69, 95% CI 1.40 to 3.98, P = 0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD = 1.49, 95% CI 0.28 to 2.71, P = 0.016; macroalbuminuria vs microalbuminuria: SMD = 0.93, 95% CI 0.34 to 1.52, P = 0.002).
CONCLUSIONS
Our current meta-analysis demonstrates that serum level of YKL-40 is increased in DM and positively associated with the severe degree of albuminuria. Therefore, we suggest that YKL-40 could be considered to be detected, along with other inflammatory markers, if DM, especially DN, is suspected.
PubMed: 33446257
DOI: 10.1186/s13098-021-00624-9 -
Diagnostics (Basel, Switzerland) Nov 2020There is a lack of prediction markers for early diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). The aim of this systematic review and...
There is a lack of prediction markers for early diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis was to evaluate the performance of two promising biomarkers, urinary kidney injury molecule 1 (uKIM-1) and Chitinase-3-like protein 1 (YKL-40) in the diagnosis of early diabetic nephropathy in type 2 diabetic patients. A comprehensive search was performed on PubMed by two reviewers until May 2020. For each study, a 2 × 2 contingency table was formulated. Sensitivity, specificity, and other estimates of accuracy were calculated using the bivariate random effects model. The hierarchical summary receiver operating characteristic curve hsROC) was used to pool data and evaluate the area under curve (AUC). The sources of heterogeneity were explored by sensitivity analysis. Publication bias was assessed using Deek's test. The meta-analysis enrolled 14 studies involving 598 healthy individuals, 765 T2DM patients with normoalbuminuria, 549 T2DM patients with microalbuminuria, and 551 T2DM patients with macroalbuminuria, in total for both biomarkers. The AUC of uKIM-1 and YKL-40 for T2DM patients with normoalbuminuria, was 0.85 (95%CI; 0.82-0.88) and 0.91 (95%CI; 0.88-0.93), respectively. The results of this meta-analysis suggest that both uKIM-1 and YKL-40 can be considered as valuable biomarkers for the early detection of DN in T2DM patients with the latter showing slightly better performance than the former.
PubMed: 33171707
DOI: 10.3390/diagnostics10110909