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Frontiers in Pharmacology 2020Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies...
Astragaloside IV (AS-IV) has a variety of biological activities and is widely used to treat kidney diseases. We conducted a systematic review of 24 animal studies including 424 animals to evaluate the efficacy of AS-IV for diabetic nephropathy (DN); all current possible mechanisms were summarized. A search strategy was applied to eight databases from inception to June 2020. The CAMARADES 10-item quality checklist and Rev-Man 5.3 software were used to analyze the risks of bias of each study and data regarding outcome measures, respectively. The mean study quality score was 5.4 points (range 3-8 points). Meta-analyses data and comparisons between groups showed that AS-IV significantly slowed the progression of pathological signs in the kidney including glomeruli and tubules, increasing creatinine clearance rate, decreasing blood urea nitrogen, serum creatinine, 24-h urinary neutrophil gelatinase-associated lipocalin and N-acetyl--D-glucosaminidase, 24-h urinary albumin, 24-h urinary microalbumin and HbA1c. There were no significant differences between experimental and control groups with respect to mortality or levels of alanine aminotransferase and aspartate aminotransferase. In terms of the possible mechanisms of treatment of DN, AS-IV acts through antifibrotic, antioxidant, and antiapoptotic mechanisms, thereby alleviating endoplasmic reticulum stress, inhibiting mitochondrial fission, and increasing autophagic activity. Taken together, our findings suggest that AS-IV is a multifaceted renoprotective candidate drug for DN.
PubMed: 32695006
DOI: 10.3389/fphar.2020.00988 -
Nutricion Hospitalaria Mar 2013Obesity, as a central piece inside metabolic syndrome, is associated with early chronic kidney disease (CKD). In addition, several observational, cross sectional, and... (Review)
Review
INTRODUCTION
Obesity, as a central piece inside metabolic syndrome, is associated with early chronic kidney disease (CKD). In addition, several observational, cross sectional, and longitudinal studies have demonstrated that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of CKD including diabetic nephropathy. This implies that when obesity is reversed, many CKD risk factors and CKD itself could be favorably influenced. So all measures aimed at weight loss are recommended to minimize risks from obesity-related conditions and generate improvements in the metabolic profile. Recent evidence shows that bariatric surgery (BS) can revert or improve proteinuria and CKD in morbidly obese patients.
OBJECTIVES AND METHODS
The present review is aimed to provide the evidence regarding the beneficial effects of weight loss after BS in different stages of CKD including kidney transplant recipients, with an special focus on the beneficial effect in reducing or improving proteinuria and renal failure. Furthermore, this updated systematic review of the literature analyzes potential adverse effects that BS could induce not only on renal function but also on morbidity and mortality risk in perioperative and postoperative period.
CONCLUSIONS
Results from the different case reports, meta analysis as well as systematic review of clinical trials show that obesity treatment by way of lifestyle changes, pharmacotherapies and BS can reduce proteinuria and help to prevent loss of renal function. Also BS may reduce complications, and allow obese patients with end-stage renal disease to undergo kidney transplantation with good results.
Topics: Bariatric Surgery; Diabetic Nephropathies; Humans; Obesity; Renal Insufficiency, Chronic; Risk Factors
PubMed: 23834048
DOI: 10.3305/nh.2013.28.sup2.6715 -
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 -
Medicine Sep 2017Orthostatic hypotension (OH) is a major clinical sign of cardiovascular autonomic dysfunction in diabetic patients. Our aim was to quantitatively evaluate the prevalence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Orthostatic hypotension (OH) is a major clinical sign of cardiovascular autonomic dysfunction in diabetic patients. Our aim was to quantitatively evaluate the prevalence and risk factors of OH in patients with diabetes mellitus (DM) and assess its prognosis.
METHODS
A comprehensive search of the PubMed, Embase, China National Knowledge Infrastructure, VIP Chinese Journal, Wanfang, and SINOMED databases was conducted for related published work up to September 25, 2016, and manually searched eligible studies from the references in accordance with the inclusion criteria.
RESULTS
We included 21 studies in the analysis, with a total sample size of 13,772. The pooled prevalence of OH in DM was 24% (95% confidence interval [CI]: 19-28%). Potential risk factors, that is, glycosylated hemoglobin A (HbA1c) (odds ratio [OR], 1.13, 95% CI, 1.07-1.20), hypertension (OR, 1.02, 95% CI, 1.01-1.02), and diabetic nephropathy (OR, 2.37, 95% CI, 1.76-3.19), were significantly associated with OH in DM. In addition, the prognosis of OH in DM was associated with higher risk of total mortality and cardiovascular events.
CONCLUSION
The pooled prevalence of OH in DM appears high. HbA1c, hypertension, and diabetic nephropathy are risk factors for OH in DM. OH indicates poor prognosis in diabetic patients. Attention should be focused on diabetic patients with the stated risk factors to prevent OH.
Topics: Diabetes Mellitus; Humans; Hypotension, Orthostatic; Prevalence; Prognosis; Risk Factors
PubMed: 28885363
DOI: 10.1097/MD.0000000000008004 -
Frontiers in Endocrinology 2024Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN.
METHODS
We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated.
RESULTS
Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test.
CONCLUSION
Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.
Topics: Humans; Diabetic Nephropathies; Retinol-Binding Proteins, Plasma; Diabetes Mellitus, Type 2; Biomarkers; Sensitivity and Specificity
PubMed: 38711978
DOI: 10.3389/fendo.2024.1356131 -
Annals of Palliative Medicine Nov 2021Diabetic nephropathy (DN) is a secondary disease of diabetes and could cause serious renal damage. This article aimed to investigate the effect of statins on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic nephropathy (DN) is a secondary disease of diabetes and could cause serious renal damage. This article aimed to investigate the effect of statins on the treatment of early DN.
METHODS
The databases were searched: Embase (January 2000-August 2021), PubMed (January 2000-August 2021), Cochrane [randomized controlled trial (RCT) database], Ovid (January 2000-August 2021), and clinicaltrials.gov (January 2000-August 2021) to obtain RCT literature related to statin intervention and DN. After screening, the risk of bias assessment was performed using the RevMan 5.4 software bias assessment tool, which was then used to perform the meta-analysis and obtain the therapeutic effects of statins by estimating indicators such as estimated glomerular filtration rate (eGFR), serum creatinine (SCR), total cholesterol (TC) level, total triglyceride (TG), and high-sensitivity C-reactive protein (hs-CRP).
RESULTS
A total of 9 articles, 3,426 patients, and 5 types of statins were included. Meta-analysis showed that after treatment, eGFR in the experimental group was higher than in the control group [mean difference (MD) =5.80; 95% confidence interval (CI): (2.21, 9.40); P=0.002], SCR was lower than in the control group [MD =-0.46; 95% CI: (-0.69, -0.24); P<0.0001], hs-CRP level was lower than in the control group [MD =-1.20; 95% CI: (-2.05, -0.36); P=0.005], TC level was lower than in the control group [MD =-54.09; 95% CI: (-68.02, -40.16); P<0.00001], and TG level was lower than that in the control group [MD =-42.19; 95% CI: (-55.54, -28.84); P<0.00001].
DISCUSSION
Statins can significantly increase eGFR, reduce SCR, decrease CRP level, and decrease blood lipid level in the treatment of DN, thus reducing the inflammatory response and protecting the kidney.
Topics: C-Reactive Protein; Diabetes Mellitus; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 34872280
DOI: 10.21037/apm-21-2673 -
PloS One 2017Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.
STUDY DESIGN
Systematic review and meta-analysis.
POPULATION
Adults with DKD (either secondary to type 1 or 2 diabetes mellitus).
SEARCH STRATEGY AND SOURCES
Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction.
INTERVENTION
Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination.
OUTCOMES
Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.
RESULTS
From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking.
LIMITATIONS
Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.
CONCLUSIONS
In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.
Topics: Antioxidants; Diabetic Nephropathies; Dietary Supplements; Disease Progression; Humans
PubMed: 28570649
DOI: 10.1371/journal.pone.0178699 -
EClinicalMedicine Mar 2024Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on...
BACKGROUND
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain.
METHODS
In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148).
FINDINGS
This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years.
INTERPRETATION
BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD.
FUNDING
Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.
PubMed: 38374967
DOI: 10.1016/j.eclinm.2024.102482 -
Clinical Therapeutics Nov 2020Irbesartan is widely used clinically in the treatment of diabetic nephropathy (DN). It is believed that piperazine ferulate (PF) combined with irbesartan could result in... (Meta-Analysis)
Meta-Analysis
PURPOSE
Irbesartan is widely used clinically in the treatment of diabetic nephropathy (DN). It is believed that piperazine ferulate (PF) combined with irbesartan could result in an improved efficacy in the treatment of DN. We present the latest meta-analysis that details the combination of PF and irbesartan therapy.
METHODS
Before January 31, 2020, we searched various electronic databases for appropriate articles. Our search was not restricted by keyword or language. We then filtered all articles using certain criteria and assessed the quality of the qualified studies.
FINDINGS
The meta-analysis included 12 trials that involved 1300 patients (650 in the experimental group and 650 in the control group). The ages of the patients ranged from 30 to 79 years. Compared with irbesartan alone, the total effective rate of PF combined with irbesartan was significantly higher (odds ratio [OR] = 4.95; 95% CI, 3.11-7.58; P < 0.0001). The blood glucose level was controlled by significantly decreasing the fasting plasma glucose level (mean difference [MD] = -1.40; 95% CI, -2.70 to -0.11; P = 0.03) and 2-h plasma glucose level (MD = -1.65; 95% CI, -2.49 to -0.82; P < 0.0001). The combination therapy significantly decreased the levels of serum creatinine (MD = -10.24; 95% CI, -15.25 to -5.23; P < 0.0001), 24-h urinary protein (MD = -0.07; 95% CI, -0.09 to -0.05; P < 0.0001), urinary albumin excretion rate (MD = -22.52; 95% CI, -30.20 to -14.84; P < 0.0001), urinary β-microglobulin (MD = -0.15; 95% CI, -0.17 to -0.13; P < 0.0001), and blood urea nitrogen (MD = -1.54; 95% CI, -2.36 to -0.72; P = 0.0002), which was beneficial for improving and protecting renal function. The renal microcirculation was improved by significantly decreasing the whole blood viscosity low shear (MD = -1.41; 95% CI, -1.84 to -0.99; P < 0.0001), whole blood viscosity high shear (MD = -0.54; 95% CI, -0.63 to -0.45; P < 0.0001), whole blood viscosity (MD = -1.31; 95% CI, -1.79 to -0.83; P < 0.0001), whole blood reduction viscosity (MD = -1.42; 95% CI, -1.79 to -1.06; P < 0.0001), platelet aggregation rate (MD = -0.42; 95% CI, -0.50 to -0.35; P < 0.0001), plasma viscosity (MD = -13.02; 95% CI, -15.47 to -10.56; P < 0.0001), and fibrinogen content (MD = -0.25; 95% CI, -0.42 to -0.09; P = 0.003).
IMPLICATIONS
PF combined with irbesartan could improve the efficiency in the treatment of DN. However, these results should be handled carefully. These findings should be verified by several rigorous randomized controlled trials.
Topics: Adult; Aged; Blood Urea Nitrogen; Creatinine; Diabetic Nephropathies; Humans; Irbesartan; Middle Aged; Piperazine
PubMed: 33158581
DOI: 10.1016/j.clinthera.2020.09.013 -
Journal of Nephrology May 2023Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and... (Review)
Review
BACKGROUND
Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria.
OBJECTIVE
We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients.
RESULTS
A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting.
CONCLUSIONS
Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Cardiovascular Diseases; Mineralocorticoids; Renal Insufficiency, Chronic; Heart Failure; Diabetic Nephropathies
PubMed: 36422853
DOI: 10.1007/s40620-022-01492-w