-
Frontiers in Pharmacology 2021Rhubarb, also known as Da Huang, is a traditional Chinese medicine, and it was often used as a laxative in the past. Recently, multiple studies have applied rhubarb to...
Rhubarb, also known as Da Huang, is a traditional Chinese medicine, and it was often used as a laxative in the past. Recently, multiple studies have applied rhubarb to treat diabetic nephropathy (DN). Anthraquinones, including emodin and rhein, have been extracted from rhubarb and used to explore the effective components and possible mechanisms of rhubarb for DN. Evaluating the efficacy of rhubarb may provide a scientific reference for the clinical application of rhubarb for the treatment of DN. 1) To evaluate the efficacy of rhubarb in the treatment of DN; 2) To identify the most effective ingredient of rhubarb for DN; 3) To explore the specific mechanism of rhubarb in treating DN. Data sources: related studies were identified by searching Cochrane Library, Ovid-EMBASE, PubMed, SinoMed, WanFang, VIP, CNKI, and other Chinese magazines. Assessment and analysis: SYRCLE's risk of bias tool for animal studies was used to assess the quality of articles. The meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Data analysis adopted RevMan 5.3 and STATA 12.0 software. This study was published in the register with PROSPERO, number CRD42020204701. Aggregated data were collected from 27 eligible studies. The results illustrated an intense improvement in the following outcomes in rhubarb-treated animals with DN ( < 0.05): blood glucose, serum creatinine (Scr), blood urea nitrogen (BUN), albumin creatinine ratio (ACR), urine protein (UP), urinary albumin excretion (UAE), renal index (two kidneys weight/body weight, KW/BW), tubulointerstitial injury index (TII), transforming growth factor-beta1 (TGF-β1) mRNA and protein, alpha-smooth muscle actin (α-SMA) protein, and E-cadherin (E-cad) protein. Of these, DN animals with rhubarb exhibited a significantly higher level of E-cad protein. In addition, the level of the other outcomes mentioned above decreased significantly, while there was no significant association between the intervention and nephrin protein ( > 0.05). This systematic review and meta-analysis demonstrated that rhubarb has a positive therapeutic effect on animals with DN, which may provide confidence and some theoretical reference for clinical application to a certain extent.
PubMed: 34177560
DOI: 10.3389/fphar.2021.602816 -
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 -
Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
Frontiers in Endocrinology 2021The aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic... (Meta-Analysis)
Meta-Analysis
AIM
The aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic nephropathy (DN) and to resolve the conflict between medicine guidance and clinical practice for TG application.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials involving TG application in treating DN. We extensively searched PubMed, Cochrane Library, CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Trial Registry, and WHO International Clinical Trial Registration Platform till November 2020, along with grey literature for diabetes and all other relevant publications to gather eligible studies. Based on the preset inclusion and exclusion criteria, document screening, quality assessment of methodology, and data extraction was conducted by two researchers independently. The methodological quality was assessed by the Cochrane risk test from the Cochrane Handbook 5.2, and then analyses were performed by Review Manager 5.3 (Rev Man 5.3). The quality of output evidence was classified by GRADE.
RESULTS
Thirty-one eligible studies (2764 patients) were included for this meta-analysis. Our study results showed a comparable significant decrease in the 24 h-UTP and blood creatinine levels in DN patients from both 3-month and 6-month TG treatment groups, compared with the routine symptomatic treatment alone. To the contrary of the findings from the included studies, our results showed that the occurrence of serious adverse reaction events was significantly higher in the TG treated group with 6 months of treatment duration compared to that of 3 months of the treatment course. However, the total AR ratio was slightly varied while increasing the percent of severe adverse events. GRADE assessment indicated that the quality of evidence investigating TG-induced adverse reactions was moderate and that for 24 h-UTP and blood creatinine indicators were considerably low.
CONCLUSION
Combinatorial treatment regimen including TG can significantly decrease the pathological indicators for DN progression, while it can also simultaneously predispose the patient to a higher risk for developing severe adverse events, as the medicine guidance indicates. Notably, even in 3-month of course duration smaller percent of severe adverse events can get to a fatal high percent and is likely to increase proportionally as the TG treatment continues. This suggests that TG-mediated DN treatment duration should be optimized to even less than 3 continuous months to avoid adverse event onset-associated further medical complications in DN patients. In clinical practice, serious attention should be paid to these severe side-effects even in a course normally considered safe, and importantly more high-quality studies are urgently warranted to obtain detailed insights into the balance between the efficacy and safety profiles of TG application in treating DN.
Topics: Diabetic Nephropathies; Glycosides; Humans; Time Factors; Tripterygium
PubMed: 33959100
DOI: 10.3389/fendo.2021.656621 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
International Urology and Nephrology Dec 2023In recent years, increasing evidence has shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) drugs have potential renoprotective effects in patients with... (Meta-Analysis)
Meta-Analysis
PURPOSE
In recent years, increasing evidence has shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) drugs have potential renoprotective effects in patients with diabetes mellitus (DM). However, the renal protective effect of SGLT2i in non-diabetic nephropathy patients has not been extensively demonstrated. In this systematic review and meta-analysis, we aimed to evaluate the renal protective effect and safety of SGLT2i in non-diabetic nephropathy patients.
METHODS
we searched for relevant clinically randomised controlled trials and analyzed the effects of SGLT2i on estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (UACR), and systolic blood pressure (SBP) and the incidence of adverse events in patients with non-diabetic nephropathy.
RESULTS
We collated and analysed clinical data from six groups of patients with nondiabetic nephropathy. It was found that the SGLT2i significantly delayed the decline in eGFR [MD = 1.35 ml/min/1.73 m, 95% CI 0.84, 1.86), P < 0.0001]. Furthermore, the SGLT2i significantly reduced UACR [MD = - 24.47% l, 95% CI (- 38.9, -10.04), P = 0.0009], and showed a greater decrease in SBP [MD = - 4.13 mmHg, 95% CI (- 7.49, - 0.77), P = 0.02]. There was no significant difference in the incidence of adverse reactions between dapagliflozin/empagliflozin and the control group [OR = 1.14, 95% CI (0.88, 1.47), P = 0.33].
CONCLUSION
This study shows that SGLT2i help to delay the progression of non-diabetic kidney disease. Therefore, SGLT2i may contribute to the general treatment of nondiabetic nephropathy.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Renal Insufficiency, Chronic; Kidney
PubMed: 37046125
DOI: 10.1007/s11255-023-03586-1 -
Journal of Ethnopharmacology Feb 2023Ginseng is one of the most widely used herbs in the world for the treatment of various diseases, and ginsenoside is the representative bioactive component in ginseng.... (Meta-Analysis)
Meta-Analysis
ETHNOPHARMACOLOGICAL RELEVANCE
Ginseng is one of the most widely used herbs in the world for the treatment of various diseases, and ginsenoside is the representative bioactive component in ginseng. There have been many in vivo studies on ginsenoside for the treatment of diabetic nephropathy (DN), the most common diabetic microvascular complication and the main cause of diabetic morbidity and mortality.
AIM OF THE STUDY
The purpose of this study is to evaluate the efficacy of ginsenosides on DN by preclinical evidence and meta-analysis. Meanwhile, the main possible action mechanisms of ginsenosides against DN were also summarized.
MATERIALS AND METHODS
We systematically searched PubMed, WOS, Embase, Cochrane, WanFang, Cqvip, CNKI and CBM databases from January 1, 2000, to November 15, 2021, to evaluate the animal experiments of ginsenosides for the treatment of DN. Finally, 30 animal experiments were included. Twelve outcome measures, including renal function indicators (24-h urine protein, serum creatinine, urea nitrogen, creatinine clearance, uric acid, urinary albumin to creatinine ratio), oxidative stress biomarkers (GPX, MDA, SOD), inflammatory factors (IL-1, IL-6, TNF-α) were obtained by using RevMan 5.4 software for meta-analysis.
RESULTS
The results showed that except for no significant difference in CCr, other indicators such as 24h UP, SCr, blood urea nitrogen, uric acid and UACR were significantly decreased. It showed that ginsenoside could improve renal function in diabetes. Meanwhile ginsenoside significantly up-regulated antioxidant enzymes SOD and GPX, down-regulated MDA and inflammatory factors IL-1, IL-6 and TNF-α, indicating that ginsenoside may have antioxidant and anti-inflammatory effects.
CONCLUSION
Ginsenoside can protect against the renal failure in diabetes through anti-inflammation, anti-oxidation, anti-renal fibrosis, anti-apoptosis/pyroptosis, regulation of blood glucose/lipid metabolism, etc. Which provides preclinical evidence for the application of ginsenoside in the treatment of DN.
Topics: Animals; Antioxidants; Creatinine; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Ginsenosides; Interleukin-1; Interleukin-6; Panax; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Uric Acid
PubMed: 36341813
DOI: 10.1016/j.jep.2022.115860 -
Current Diabetes Reviews 2022Diabetic nephropathy (DN) is kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies on animals...
BACKGROUND
Diabetic nephropathy (DN) is kidney dysfunction, which occurs due to elevated urine albumin excretion rate and reduced glomerular filtration rate. Studies on animals have shown that alpha-lipoic acid (ALA) supplementation can reduce the development of DN.
OBJECTIVES
We performed a systematic review and meta-analysis to examine the effects of ALA supplementation on biological indices (albumin, creatinine, etc.) indicative of human DN.
METHODS
The search procedure included PubMed Central, Embase, Cochrane Library (trials), and Web of Science (protocol registration: INPLASY202060095).
RESULTS
We found that ALA supplementation decreased 24h urine albumin excretion rate in patients with diabetes (standardized mean difference=-2.27; confidence interval (CI)=(-4.09)-(-0.45); I=98%; Z=2.44; p=0.01). A subgroup analysis revealed that the results of studies examining only ALA did not differ from those examined ALA in combination with additional medicines (Chisquared= 0.19; p=0.66; I=0%), while neither ALA nor ALA plus medication had an effect on 24h urine albumin excretion rate (p>0.05). Also, ALA supplementation decreased urine albumin mg/l (mean difference (MD)=-12.95; CI=(-23.88)-(-2.02); I=44%; Z=2.32; p=0.02) and urine albumin to creatinine ratio (MD=-26.96; CI=(-35.25)-(-18.67); I=0%; Z=6.37; p<0.01) in patients with diabetes. When the studies examining ALA plus medication were excluded, it was found that ALA supplementation had no effect on urine albumin mg/l (p>0.05) but did significantly decrease urine albumin to creatinine ratio (MD=-25.88, CI=(34.40-(-17.36), I=0%, Z=5.95, p<0.00001).
CONCLUSION
The available evidence suggests that ALA supplementation does not improve biological indices that reflect DN in humans. Overall, we identified limited evidence, and therefore, the outcomes should be considered with caution.
Topics: Albumins; Animals; Creatinine; Diabetes Mellitus; Diabetic Nephropathies; Dietary Supplements; Female; Humans; Male; Thioctic Acid
PubMed: 34521329
DOI: 10.2174/1573399817666210914103329 -
Advances in Therapy Mar 2021Micro- and macrovascular complications of diabetes are leading morbidities in the world population. They are responsible not only for increased mortality but also severe... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Micro- and macrovascular complications of diabetes are leading morbidities in the world population. They are responsible not only for increased mortality but also severe disabilities, which jeopardize quality of life (e.g., blindness, walking limitations, and renal failure requiring dialysis). The new antidiabetic agents (e.g., glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter inhibitors) are increasingly recognized as breakthrough agents in the treatment of diabetes and prevention of diabetic complications. However, drugs effective in preventing and treating diabetic disabilities are still needed and sulodexide could be one of those able to address the unmet clinical needs of the new antidiabetic agents.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings, and journal supplements. Any study monitoring any effect of sulodexide in subjects with diabetes, in relation to renal, vascular, and ocular complication, was considered. Treatment effects were estimated using standardized mean differences (SMDs), mean differences (MDs), and risk ratios (RRs), as appropriate. We calculated 95% confidence interval (CIs) and heterogeneity (Q, tau, and I).
RESULTS
The search found 45 studies with 2817 participants (mean age 57 years; 63% male). The 26 randomized controlled studies included 2074 participants (mean age 58.8 years; 66% male). Sulodexide reduced the impact of diabetic retinopathy; increased the pain-free and maximal walking distance in peripheral arterial disease; accelerated the healing of diabetes-associated trophic ulcers; and decreased the rate of albumin excretion in subjects with nephropathy. The risk of adverse events (AEs) was not different between sulodexide and controls.
CONCLUSION
Sulodexide has a beneficial effect on the ocular, peripheral arterial disease, trophic ulcers, and renal complications of diabetes without increasing the risk of AEs.
Topics: Diabetes Mellitus; Female; Glycosaminoglycans; Humans; Hypoglycemic Agents; Male; Middle Aged; Quality of Life
PubMed: 33502688
DOI: 10.1007/s12325-021-01620-1 -
Diabetes Research and Clinical Practice Sep 2022To assess the efficacy of low-protein diets (LPD) on cardiovascular risk factors and kidney function in diabetic nephropathy (DN) based on randomized controlled trials... (Meta-Analysis)
Meta-Analysis Review
Impact of low-protein diet on cardiovascular risk factors and kidney function in diabetic nephropathy: A systematic review and meta-analysis of randomized-controlled trials.
AIM
To assess the efficacy of low-protein diets (LPD) on cardiovascular risk factors and kidney function in diabetic nephropathy (DN) based on randomized controlled trials (RCTs).
METHODS
A comprehensive systematic search was undertaken in PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases from inception until January 2022 without using time or language restrictions. RCTs which reported the effects of LPD on cardiovascular risk factors and kidney function in DN were considered.
RESULTS
The results of the present study showed that a LPD significantly reduces urinary urea (WMD: -244.49 g/day, 95 % CI: -418.83, -70.16, P = 0.006) and HbA1c (WMD: -0.20, 95 % CI: -0.39, -0.01, P = 0.036) levels. However, the results did not show neither significant nor beneficial effect on other renal function and cardiovascular risk factors. Furthermore, the results of subgroup analysis showed LPD caused a further decrease in HbA1c during the follow-up period of ≤ 24 weeks, protein intake less than 0.8 g/kg/d and in individuals younger than 50 years. Albuminuria also showed a greater reduction in people under the age of 50 with type 1 diabetes (DMT1) following a LPD.
CONCLUSION
The results of the present study showed that LPD significantly reduces urinary urea and HbA1c.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Diet, Protein-Restricted; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Kidney; Randomized Controlled Trials as Topic; Urea
PubMed: 36084854
DOI: 10.1016/j.diabres.2022.110068