-
Frontiers in Endocrinology 2022Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease... (Meta-Analysis)
Meta-Analysis
Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease with an increasing prevalence. Presently there is no non-invasive method for differential diagnosis, and an efficient target therapy is lacking. Extracellular vesicles (EV), including exosomes, microvesicles, and apoptotic bodies, are present in various body fluids such as blood, cerebrospinal fluid, and urine. Proteins in EV are speculated to be involved in various processes of disease and reflect the original cells' physiological states and pathological conditions. This systematic review is based on urinary extracellular vesicles studies, which enrolled patients with DN and investigated the proteins in urinary EV. We systematically reviewed articles from the PubMed, Embase, Web of Science databases, and China National Knowledge Infrastructure (CNKI) database until January 4, 2022. The article quality was appraised according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The methodology of samples, isolation and purification techniques of urinary EV, and characterization methods are summarized. Molecular functions, biological processes, and pathways were enriched in all retrievable urinary EV proteins. Protein-protein interaction analysis (PPI) revealed pathways of potential biomarkers. A total of 539 articles were retrieved, and 13 eligible records were enrolled in this systematic review and meta-analysis. And two studies performed mass spectrometry to obtain the proteome profile. Two of them enrolled only T1DM patients, two studies enrolled both patients with T1DM and T2DM, and other the nine studies focused on T2DM patients. In total 988 participants were enrolled, and DN was diagnosed according to UACR, UAER, or decreased GFR. Totally 579 urinary EV proteins were detected and 28 of them showed a potential value to be biomarkers. The results of bioinformatics analysis revealed that urinary EV may participate in DN through various pathways such as angiogenesis, biogenesis of EV, renin-angiotensin system, fluid shear stress and atherosclerosis, collagen degradation, and immune system. Besides that, it is necessary to report results compliant with the guideline of ISEV, in orderto assure repeatability and help for further studies. This systematic review concordance with previous studies and the results of meta-analysis may help to value the methodology details when urinary EV proteins were reported, and also help to deepen the understanding of urinary EV proteins in DN.
Topics: Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular Vesicles; Humans; Proteome
PubMed: 36034457
DOI: 10.3389/fendo.2022.866252 -
BMC Research Notes Aug 2018This meta-analysis was undertaken to estimate the prevalence of diabetic nephropathy and its association with hypertension in diabetics of sub-Saharan African countries. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This meta-analysis was undertaken to estimate the prevalence of diabetic nephropathy and its association with hypertension in diabetics of sub-Saharan African countries.
RESULTS
A total of 27 studies were included for the meta-analysis. The pooled overall prevalence of diabetic nephropathy was 35.3 (95% CI 27.46-43.14). In sub-group analyses by types of diabetes and regions, for instance, the prevalence was 41.4% (95% CI 32.2-50.58%) in type-2 diabetes mellitus and 29.7% (95% CI 14.3-45.1%) in Eastern Africa. Pooled point estimates from included studies revealed an increased risk of diabetic nephropathy with hypertension compared to without hypertension (OR = 1.67, 95% CI 1.31, 2.14). Diabetic nephropathy is a common complication in diabetic patients. Diabetic nephropathy complication is significantly higher in hypertensive patients. A preventive strategy should be adopted or planned to reduce diabetes mellitus and its complication of neuropathy, particularly in hypertensive.
Topics: Africa South of the Sahara; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypertension
PubMed: 30081966
DOI: 10.1186/s13104-018-3670-5 -
Cureus Dec 2022Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against... (Review)
Review
Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against using these drugs in severe diabetic kidney disease. Consequently, the choice of anti-diabetic medicine in various stages of diabetic nephropathy should balance the benefits and risks to the patient. We aim to synthesize available evidence on the effectiveness and safety of metformin concerning sulfonylureas in patients with diabetic renal disease. The COSMOS-E (Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology) and MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology) guidelines were followed when designing the systematic review. The present study assessed the effectiveness of metformin and sulphonylurea monotherapy regarding renal function. Studies published from 2001 to 2022 were included. We have identified 570 records from PubMed, BioMed Central, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ScienceDirect, and PLoS (The Public Library of Science) Medicine databases. Eight cohort studies met the inclusion criteria. All studies reported adjusted hazard ratios with confidence limits. Metformin was found to be more effective in the following events: all-cause mortality, GFR (glomerular filtration rate), ESRD (end-stage renal disease) or death events, one-year risk of death or end-stage renal disease, cardiovascular events, heart failure hospitalization, and hypoglycemic episodes. However, metformin was less effective in acute renal replacement therapy, end-stage renal disease, and/or death, with a one-year risk of acute dialysis. Lactic acidosis was not significant with metformin. The present study recommends that metformin therapy is safe compared to sulfonylurea therapy in diabetic nephropathy patients, provided that the contraindications given in the guidelines are strictly adhered to.
PubMed: 36628027
DOI: 10.7759/cureus.32286 -
International Journal of Molecular... Dec 2022Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present... (Meta-Analysis)
Meta-Analysis Review
Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. , , , , , , , , , , , , , and were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small.
Topics: Humans; Diabetic Nephropathies; Fibrosis; Genetic Association Studies; Renal Insufficiency, Chronic; Signal Transduction; Diabetes Mellitus
PubMed: 36499658
DOI: 10.3390/ijms232315331 -
Food & Function May 2022Quercetin, a flavonoid possessing numerous biological activities, is reported to improve renal injury in diabetic animals. Here, the aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Quercetin, a flavonoid possessing numerous biological activities, is reported to improve renal injury in diabetic animals. Here, the aim of this systematic review and meta-analysis is to assess the effect of quercetin on diabetic nephropathy and summarize its possible mechanisms. We searched in four databases PubMed, Web of Sciences (WOS), Cochrane and Embase from inception to May 2021 and ultimately included 20 animal studies in this review. A total of 12 outcome measurements including renal function indexes, oxidative stress biomarkers and inflammatory cytokines were extracted for meta-analysis using RevMan 5.4 software. Apart from creatinine clearance and uric acid with no significant difference, quercetin significantly decreased the levels of renal index, serum/plasma creatinine (SCr), blood urea nitrogen (BUN), urine protein, urine albumin, malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and increased superoxide dismutase (SOD) and catalase (CAT) activity. In short, quercetin improves renal function and attenuates the renal oxidative stress level and inflammatory response in DN animal models. Its possible action mechanisms include anti-oxidation, anti-inflammation, anti-fibrosis, and regulation of renal lipid accumulation.
Topics: Animals; Antioxidants; Creatinine; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Kidney; Male; Oxidative Stress; Quercetin
PubMed: 35416188
DOI: 10.1039/d1fo03958j -
Journal of Taibah University Medical... Jun 2023Diabetic nephropathy causes cardiovascular complications among individuals with diabetes which results in decreased kidney function and overall physical decline. The... (Review)
Review
Diabetic nephropathy causes cardiovascular complications among individuals with diabetes which results in decreased kidney function and overall physical decline. The objective of this systematic review was to determine effects of exercise on various renal function parameters amond individuals with type 2 diabetes and nephropathy. It was registered with PROSPERO (CRD42020198754). Total 6 databases (PubMed/Medline, Scopus, Web of Science, CINAHL, ProQuest, and Cochrane) were searched. Among 1734 records, only four randomized controlled trials were included. The review included a total of 203 participants (103 in the intervention group and 100 in the control/standard group) with type 2 diabetic nephropathy or stage 2,3, or 4 of chronic kidney disease. The meta-analysis showed no effects of exercise on serum creatinine, serum cystatin c and varied eGFR equations. However, exercise decreased urinary albumin to creatinine ratio, urinary protein to creatinine ratio, serum urea nitrogen, creatinine clearance, and urinary protein excretion while increasing urea clearance. Limited evidence on the reno-protective role of exercise demands future research in this direction.
PubMed: 36818178
DOI: 10.1016/j.jtumed.2022.11.002 -
Evidence-based Complementary and... 2019Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Many trials have shown that could further improve proteinuria and protect kidney...
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Many trials have shown that could further improve proteinuria and protect kidney function in patients with DN when added to a renin-angiotensin system (RAS) blocker. A systematic assessment of the efficacy and safety of in DN is essential. Eight electronic databases were searched to identify eligible trials published from inception to December 2017. The Cochrane Risk of Bias Tool was used to evaluate the methodological quality of eligible studies. Seventy-two studies with 5,895 participants were identified. The methodological quality of included studies was generally low. The results indicated that, compared to a RAS blocker, combined treatment of with a RAS blocker was more effective for 24h urinary protein (24h UP) (mean difference [MD], -0.39 [95% confidence interval [CI], -0.46 to -0.33] g/d; P<0.00001), urinary albumin excretion rate (UAER)(MD, -19.90 [95% CI, -22.62 to -17.18] g/min; P<0.00001), 24h UP reduction rate (risk ratio [RR], 1.43; 95% CI, 1.26-1.63; P<0.00001), normalization of UAER (RR, 1.48; 95% CI, 1.29-1.70; P<0.00001), and serum creatinine (SCr) (MD, -7.35 [95% CI, -9.95 to -4.76] umol/L; P<0.00001). None of these trials reported the ESRD rate. No statistically significant difference occurred between combined with a RAS blocker and a RAS blocker alone in estimated glomerular filtration rate (eGFR) (MD, 4.43 [95% CI, -1.68 to 10.54] mL/min; P=0.16). did not increase the rates of adverse drug events. in addition to a RAS blocker was effective and safe to further improve proteinuria and protect kidney function in patients with DN. However, due to the generally low methodological quality, significant heterogeneity, and publication bias, high-quality randomized controlled trials are required to confirm these findings before the routine use of can be recommended.
PubMed: 31118973
DOI: 10.1155/2019/9679234 -
Frontiers in Pharmacology 2023is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years.... (Review)
Review
is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) ( = 0.0009) and blood urea nitrogen (BUN) ( < 0.00001) levels, reducing proteinuria ( < 0.00001) and fasting blood glucose (FBG) ( < 0.0001), improving kidney indices ( < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
PubMed: 37621314
DOI: 10.3389/fphar.2023.1192694 -
Endocrinology, Diabetes & Metabolism Jan 2021With increasing numbers of patients with type 2 diabetes mellitus (T2DM) worldwide, the number of associated diabetic foot complications might also increase. This...
AIMS
With increasing numbers of patients with type 2 diabetes mellitus (T2DM) worldwide, the number of associated diabetic foot complications might also increase. This systematic review was performed to summarize published data about risk factors for the diabetic foot (DF) syndrome in order to improve the identification of high-risk patients.
MATERIALS AND METHODS
Six electronic databases were searched for publications up to August 2019 using predefined stringent inclusion and exclusion criteria.
RESULTS
Of 9,476 identified articles, 31 articles from 28 different study populations fulfilled the criteria for our evaluation. The overall quality of the studies was good, and the risk of bias was low. There was large heterogeneity among the studies concerning study protocols and patient populations analysed. A total of 79 risk factors were analysed within this review. The majority of studies described a consistently positive association with different outcomes of interest related to DF for gender, peripheral neuropathy, retinopathy, nephropathy, poor glycaemic control, insulin use, duration of diabetes, smoking and height. For age, hypertension, dyslipidaemia and body mass index, the results remain inconsistent.
CONCLUSION
A most up-to-date literature review resulted in glycaemic control and smoking as the only amenable risk factors with a consistently positive association for DF. Due to the high personal and financial burden associated with DF and the large heterogeneity among included studies, additional longitudinal studies in large patient populations are necessary to identify more modifiable risk factors that can be used in the prediction and prevention of DF complications.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Foot; Female; Glycemic Control; Humans; Male; Middle Aged; Risk Factors; Sex Factors; Smoking; Young Adult
PubMed: 33532615
DOI: 10.1002/edm2.175 -
Phytomedicine : International Journal... Oct 2022Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data.
PURPOSE
We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis.
METHODS
Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN.
RESULTS
This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-β1, TGF-β1 mRNA, CTGF and IL-1β, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1β, TGF-β1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks.
CONCLUSIONS
Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Flavonoids; Kidney; Quercetin; Rodentia; Transforming Growth Factor beta1
PubMed: 35908521
DOI: 10.1016/j.phymed.2022.154348