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Frontiers in Pharmacology 2022Diabetic nephropathy (DN) is one of the most serious chronic micro-vascular complications of diabetes and the leading cause of end-stage kidney disease (ESRD)...
Diabetic nephropathy (DN) is one of the most serious chronic micro-vascular complications of diabetes and the leading cause of end-stage kidney disease (ESRD) worldwide, with reduced expectancy and quality of life and colossal financial and social burden worldwide. In spite of emerging treatments on DN, effective therapy on delaying the progression of DN is still lacking. In clinical practice, there are many studies focusing on (AM) capsules together with glycoside (TG) tablets in the treatment of DN, and excellent results have been obtained. The study aimed to evaluate the efficacy and safety of AM combined with TG in the treatment of DN. Databases including PubMed, Web of Science, Cochrane Library, Embase, CNKI, WF, and VIP were searched from their inception to 1 March 2022. The "risk of bias" evaluation tool produced by the Cochrane Collaboration Handbook was used for evaluating the quality of the included studies. Revman 5.3 software was used for meta-analysis. Here, 11 studies with a total of 1,072 participants were included for this meta-analysis. Our results showed that AM combined with TG plus basic treatment could lower levels of 24 h-UP [MD = -0.18; 95% CI: (-0.21, -0.14); < 0.00001], Scr [MD = -15.29; 95% CI: (-28.69, -1.88); = 0.03], and BUN [MD = -1.18; 95% CI: (-1.69, -0.68); < 0.00001]. Meanwhile, the adverse reaction rate increased in the combination group [RR = 1.88; 95% CI (1.26, 2.82); = 0.002]. Current evidence suggests that AM combined with TG may be more effective in the treatment of DN, which will be highly beneficial to further theoretical discussion and practical clinical applications. However, the safety cannot be ignored because of nearly increasing 2-fold adverse events, although they can be mitigated through systematic treatment. Meanwhile, due to low quality of the included studies, great possibility of publication bias, and large heterogeneity among different studies, the results of our review should be evaluated with more prudence and high-quality RCTs are warranted to confirm this in the future. www.crd.york.ac.uk, identifier CRD42022344359.
PubMed: 36172199
DOI: 10.3389/fphar.2022.936678 -
Annals of Palliative Medicine Mar 2022Diabetic nephropathy (DN) is one of the most typical microangiopathies caused by diabetes. It often leads enormous physiological and psychological burdens for patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic nephropathy (DN) is one of the most typical microangiopathies caused by diabetes. It often leads enormous physiological and psychological burdens for patients and seriously affects their quality of life. Therefore, effective combination therapy is necessary for these patients. In this study, we performed a meta-analysis to systematically evaluate and discuss the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of DN.
METHODS
The PubMed, Embase, Web of Science, and Medline databases were selected as the sources of the literature search, and the search was limited to studies published in English. Studies related to ACEIs and ARBs in the treatment of DN published from January 2001 to January 2021 were included in this analysis. Meta-analysis was performed to calculate the reinforcement mean difference.
RESULTS
In total, eight articles involving 1,893 cases with DN were included in this study. The results of this systematic review and meta-analysis showed that for patients with diabetic nephropathy,there were significant differences in 24-hour proteinuria [mean difference (MD) =-78.46, 95% confidence interval (95% CI): -80.25 to -76.66, P<0.00001], systolic blood pressure (MD =-9.11, 95% CI: -13.44 to -4.78, P<0.0001), and diastolic blood pressure (MD =-3.39, 95% CI: -5.68 to -1.11, P=0.004) between the combined ACEI and ARB group and the single ACEI or ARB group (P<0.05). In terms of safety, in addition to the significant difference in serum potassium (MD =0.1, 95% CI: 0.05 to 0.15, P=0.0001) between the combined ACEI and ARB group and the single drug group (P<0.1), there were no notable differences in serum creatinine (MD =0.66, 95% CI: -8.0 to 2.12, P=0.37), creatinine clearance (MD =-0.25, 95% CI: -0.62, 0.11, P=0.17), or the incidence of adverse reactions [odds ratio (OR) =1.19, 95% CI: 0.81 to 1.75, P=0.37].
DISCUSSION
A total of eight studies were included in this meta-analysis. The results showed that for patients with diabetic nephropathy, the combination of ACEI and ARB was more effective than ACEI or ARB alone, and also had higher safety.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Diabetes Mellitus; Diabetic Nephropathies; Humans; Quality of Life
PubMed: 35365039
DOI: 10.21037/apm-22-212 -
PloS One 2023Paeoniflorin (PF), the main active glucoside of Paeonia Lactiflora, has many pharmacological activities, such as inhibition of vasodilation, hypoglycemia, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paeoniflorin (PF), the main active glucoside of Paeonia Lactiflora, has many pharmacological activities, such as inhibition of vasodilation, hypoglycemia, and immunomodulation. Although the current evidence has suggested the therapeutic effects of PF on diabetic nephropathy (DN), its potential mechanism of action is still unclear.
PURPOSE
A systematic review and meta-analysis of the existing literature on paeoniflorin treatment in DN animal models was performed to evaluate the efficacy and mechanism of PF in DN animal models.
METHODS
The risk of bias in each study was judged using the CAMARADES 10-item quality checklist with the number of criteria met varying from 4 / 10 to 7 / 10, with an average of 5.44. From inception to July 2022, We searched eight databases. We used the Cochrane Collaboration's 10-item checklist and RevMan 5.3 software to assess the risk of bias and analyze the data. Three-dimensional dose/time-effect analyses were conducted to examine the dosage/time-response relations between PF and DN.
RESULTS
Nine animal studies were systematically reviewed to evaluate the effectiveness of PF in improving animal models of DN. Meta-analysis data and intergroup comparisons indicated that PF slowed the index of mesangial expansion and tubulointerstitial injury, 24-h urinary protein excretion rate, expression of anti-inflammatory mediators (mRNA of MCP-1, TNF-α, iNOS, and IL-1 β), and expression of immune downstream factors (P-IRAK1, TIRF, P-IRF3, MyD88, and NF-κBp-p65). Furthermore, modeling methods, animal species, treatment duration, thickness of tissue sections during the experiment, and experimental procedures were subjected to subgroup analyses.
CONCLUSION
The present study demonstrated that the reno-protective effects of PF were associated with its inhibition on macrophage infiltration, reduction of inflammatory mediators, and immunomodulatory effects. In conclusion, PF can effectively slow down the progression of DN and hold promise as a protective drug for the treatment of DN. Due to the low bioavailability of PF, further studies on renal histology in animals are urgently needed. We therefore recommend an active exploration of the dose and therapeutic time frame of PF in the clinic and in animals. Moreover, it is suggested to actively explore methods to improve the bioavailability of PF to expand the application of PF in the clinic.
Topics: Animals; Diabetic Nephropathies; Kidney; Adaptor Proteins, Signal Transducing; Ambulatory Care Facilities; Diabetes Mellitus
PubMed: 37733659
DOI: 10.1371/journal.pone.0282275 -
World Journal of Diabetes Nov 2020Diabetic nephropathy (DN) is the main cause of chronic kidney disease and end-stage renal disease worldwide. Although available clinical trials have shown that...
BACKGROUND
Diabetic nephropathy (DN) is the main cause of chronic kidney disease and end-stage renal disease worldwide. Although available clinical trials have shown that endothelin receptor (ER) antagonists may be a novel and beneficial drug for DN, no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.
AIM
To assess the effectiveness and safety of ER antagonists among patients with DN.
METHODS
The EMBASE, PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched without any language restrictions. Relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software. Publication bias was assessed using Egger's test with Stata/SE software.
RESULTS
We enrolled seven studies with six data sets and 5271 participants. The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40% reduction in urinary albumin-to-creatinine ratio than the control group ( < 0.0001 and = 0.02, respectively). Subgroup analysis for reductions in estimated glomerular filtration rate (eGFR) showed that for the middle-dosage subgroup, the ER antagonists group exhibited lower eGFR reduction than the control group ( < 0.00001; mean difference, 0.70 95%CI: 0.66, 0.74). Moreover, significant reductions in systolic and diastolic blood pressure were observed in the invention group.
CONCLUSION
ER blockades combined with angiotensin converting enzyme inhibitor /angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR. However, attention should be given to adverse events, including cardiac failure, anemia, and hypoglycemia, as well as serious adverse events.
PubMed: 33269066
DOI: 10.4239/wjd.v11.i11.553 -
BMC Medical Genetics Aug 2017A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus (DM) patients. Nevertheless, the results are inconclusive and inconsistent.
METHODS
We screened PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Wanfang databases for those relevant studies updated in May 2016.
RESULTS
7 studies involving 2564 subjects were recruited. We evaluated the genotypic and allelic differences between DN patients and DM controls. Overall analysis showed that no significant association was found among the ApaI, BsmI, FokI,TaqI gene polymorphisms and DN susceptibility in diabetic patients (all P values > 0.05). In the stratified analysis, TT genotype was related to DN susceptibility in Asians (TT vs Tt + tt: OR =2.21, 95% CI: 1.05-4.67, p = 0.04). The sensitivity analysis showed that the results in overall populations, Caucasians and Asians were dependable.
CONCLUSIONS
No significant association was found among the ApaI, BsmI, FokI, TaqI polymorphisms and DN risk in overall populations, the TaqI variants might related to DN susceptibility in Asians. Further researches are required to testify our meta-analysis.
Topics: Diabetic Nephropathies; Humans; Polymorphism, Genetic; Receptors, Calcitriol
PubMed: 28851298
DOI: 10.1186/s12881-017-0458-8 -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
BMC Medical Genetics Jan 2014Nitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and physiologically critical steps of nephron function. Endothelial NOS (eNOS) gene has been considered a potential candidate gene to diabetic nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3) polymorphisms have been associated with DN, however some studies do not confirm this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used in this report. Case-control studies that had diabetic patients with DN as cases and diabetic patients without nephropathy as controls, as well as that evaluated at least one of the three polymorphisms of interest were considered eligible. All studies published up until December 31st, 2012 were identified by searching electronic databases. Hardy-Weinberg equilibrium assessment was performed. Gene-disease association was measured using odds ratio estimation based on the following genetic contrast/models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model.
RESULTS
Twenty-two studies were eligible for meta-analysis (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a polymorphism, an association with DN was observed for all genetic models: allele contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28); recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with the exception for co-dominance model. As well, T-786C polymorphism showed association with all models, with exception for co-dominance model: allele contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97), recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23). For the G894T polymorphism, an association with DN was observed in allelic contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04-1.37).
CONCLUSIONS
In the present study, there was association of DN with eNOS 4b/a and T-786C polymorphism, which held in all genetic models tested, except for co-dominance model. G894T polymorphism was associated with DN only in allele contrast and in co-dominance model. This data suggested that the eNOS gene could play a role in the development of DN.
Topics: Animals; Diabetic Nephropathies; Genetic Predisposition to Disease; Humans; Nitric Oxide Synthase Type III; Polymorphism, Genetic
PubMed: 24433471
DOI: 10.1186/1471-2350-15-9 -
Journal of Biochemical and Molecular... Jun 2022Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes... (Meta-Analysis)
Meta-Analysis Review
Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes complications have provided conflicting results. This study aimed to elucidate the association between antioxidant and diabetic complications and to develop robust evidence for clinical decisions by systematic reviews and meta-analysis. PubMed, Embase, The Cochrane Library, Web of Science, Scopus databases were searched to collect clinical studies related to the efficacy of antioxidants in the treatment of diabetes complications from inception to May 5, 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The data of diabetic nephropathy (DN), diabetic nonalcoholic fatty liver disease (NAFLD), and diabetic periodontitis were collected to analyze the effect of antioxidant on diabetes and the above three complications. The meta-analysis results showed that antioxidant treatment was associated with significantly changes in the fasting plasma glucose (FPG) (standardized mean difference [SMD]: - 0.21 [95% confidence interval [CI]: - 0.33, -0.10], p < 0.001), hemoglobin A1c (HbA1c) (MD: - 0.41 [95% CI: - 0.63, -0.18], p < 0.001), total antioxidant capacity (TAC) (SMD: 0.44 [95% CI: 0.24, 0.63], p < 0.001) and malondialdehyde (MDA) (SMD: - 0.82 [95% CI: - 1.24, -0.41], p < 0.001) than the control group. Antioxidant supplements have the potential to treat three complications of diabetes. In conclusion, the meta-analysis results indicate that antioxidant treatment is effective clinically for diabetes mellitus and its complications.
Topics: Antioxidants; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dietary Supplements; Glycated Hemoglobin; Humans
PubMed: 35307907
DOI: 10.1002/jbt.23038 -
Journal of Diabetes and Metabolic... Dec 2020The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the... (Review)
Review
BACKGROUND
The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the findings are conflicting. Herein, we conducted a case-control and meta-analysis study to explore the association of PAI-1 4G5G polymorphism with risk of DNR.
METHODS
We retrieved PubMed, EMBASE, Web of Knowledge, and CNKI databases and screened eligible studies up to August 15, 2020. The strength of associations was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).
RESULTS
A total of 27 case-control studies including 16 studies with 1,825 cases case and 1,731 controls on DN and eleven studies with 1,397 cases and 1,545 controls on DR were selected. Pooled data showed that the PAI-1 4G5G polymorphism was significantly associated with DN (allele model: OR = 0.674, 95% CI 0.524-0.865, p = 0.002; homozygote model: OR = 0.536, 95% CI 0.351-0.817, p = 0.004; heterozygote model: OR = 0.621, 95% CI 0.427-0.903, p = 0.013; dominant model: OR = 0.575, 95% CI 0.399-0.831, p = 0.003; and recessive model: OR = 0.711, 95% CI 0.515-0.981, p = 0.038) and DR (homozygote model: OR = 0.770, 95% CI 0.621-0.955, p = 0.0.017) risk. Stratified analyses by ethnicity indicated that PAI-1 4G5G polymorphism was associated with DN and DR risk in Asians and Caucasians, respectively.
CONCLUSIONS
The present meta-analysis revealed that the PAI-1 4G5G polymorphism was associated with increased risk of DN and DR risk. However, well-designed large-scale clinical studies are required to further validate our results.
PubMed: 33520873
DOI: 10.1007/s40200-020-00675-1 -
PloS One 2024Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies.
METHODS
We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547.
RESULTS
A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN.
CONCLUSIONS
The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN.
Topics: Humans; Diabetic Nephropathies; Ethiopia; Risk Factors; Hyperglycemia; Hypertension; Prevalence; Diabetes Mellitus
PubMed: 38306369
DOI: 10.1371/journal.pone.0297082