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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 -
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 -
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 Renal Nutrition : the... Sep 2023Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications... (Review)
Review
Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.
Topics: Humans; Diabetic Nephropathies; Creatinine; Vitamin D; Diabetes Mellitus, Type 2; Proteinuria; Dietary Supplements
PubMed: 37302723
DOI: 10.1053/j.jrn.2023.05.006 -
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 -
Current Clinical Pharmacology 2020Diabetic Nephropathy is a frequent complication of diabetes mellitus due to functional and structural modifications in multiple kidney compartments. Probiotics have...
BACKGROUND
Diabetic Nephropathy is a frequent complication of diabetes mellitus due to functional and structural modifications in multiple kidney compartments. Probiotics have risen lately as a forthcoming therapeutic intervention but they have not been systematically evaluated in diabetic nephropathy so far. The aim of this systematic review was to evaluate randomized controlled trials and experimental studies assessing the effect of probiotic supplements on diabetic nephropathy.
METHODS
An extensive literature search was conducted through electronic databases (PubMed, Scopus, Cinahl and Medline) with the Medical Subject Headings and entry terms of "diabetic nephropathy", "diabetic renal disease" and "probiotics". The search yielded 116 results, 9 of which met the inclusion criteria for this systematic review.
RESULTS
Most of the microorganisms used in the studies belonged to the Lactobacillus and Bifidobacterium genus. The dosage ranged from 2×107 to 6×1010 CFU/ g. The form of the probiotics varied across the studies (capsules, sachets, soy milk, kefir and honey). The majority of the studies demonstrated the benefits of probiotic supplementation on the reduction of inflammation, oxidative stress and on the amelioration of renal function biomarkers in subjects with diabetic nephropathy. No major gastrointestinal adverse events were observed during the intervention time with probiotics.
CONCLUSION
Findings of this systematic review demonstrate the positive impact of probiotics on Diabetic Nephropathy without any major adverse events. Moreover, future larger randomized controlled trials with bigger samples and longer follow-up time are deemed necessary for further valid results on the effectiveness of probiotic supplementation on Diabetic Nephropathy.
Topics: Animals; Bifidobacterium; Diabetic Nephropathies; Humans; Inflammation; Lactobacillus; Oxidative Stress; Probiotics; Randomized Controlled Trials as Topic
PubMed: 32124701
DOI: 10.2174/1574884715666200303112753 -
Frontiers in Endocrinology 2019This study investigated the relationship strength between hypothyroidism and cardiovascular and renal outcomes in diabetic patients. The electronic databases PubMed,...
This study investigated the relationship strength between hypothyroidism and cardiovascular and renal outcomes in diabetic patients. The electronic databases PubMed, EmBase, and Cochrane library were screened for relevant studies published before November 2018. The outcomes included major cardiovascular events (MACEs), all-cause mortality, cardiac death, stroke, diabetic nephropathy (DN), diabetic retinopathy (DR), and chronic kidney disease (CKD). The pooled results for all outcomes were calculated using random-effects models. A total of eight studies met the inclusion criteria. The summary results indicated that hypothyroidism was not associated with the risk of MACEs (OR:1.21; 95%CI:0.68-2.16; = 0.514), all-cause mortality (OR:1.27; 95%CI:0.93-1.74; = 0.136), cardiac death (OR:1.16; 95%CI:0.89-1.52; = 0.271), stroke (OR:0.96; 95%CI: 0.49-1.88; = 0.915), and DN (OR:1.71; 95%CI:0.37-7.90; = 0.490). There was a significant association between hypothyroidism and the risk of DR (OR:1.73; 95%CI:1.08-2.77; = 0.023) and CKD (OR:1.22; 95%CI:1.10-1.36; < 0.001). These findings indicate that diabetic patients with hypothyroidism have an increased risk of DR and CKD. Additional large-scale prospective studies should be carried out to verify the prognosis of patients with diabetes and hypothyroidism.
PubMed: 31998230
DOI: 10.3389/fendo.2019.00889 -
Frontiers in Pharmacology 2022Accumulated experimental evidence suggests that resveratrol may have an effect on diabetic nephropathy by inhibiting inflammation and decreasing oxidative stress.... (Review)
Review
Accumulated experimental evidence suggests that resveratrol may have an effect on diabetic nephropathy by inhibiting inflammation and decreasing oxidative stress. However, the credibility of the evidence for this practice is unclear. Thus, we aimed to perform a systematic review and meta-analysis of animal studies to evaluate the antioxidant and anti-inflammatory properties of resveratrol when used in the treatment of diabetic nephropathy. Electronic bibliographic databases including PubMed, EMBASE, and Web of Science were searched for relevant studies. The methodological quality of animal studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Risk of Bias (SYRCLE's RoB) tool. A meta-analysis was performed based on the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.4 software. This study was registered within International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42021293784. Thirty-six qualified studies involving 726 animals were included. There was a significant association of resveratrol with the levels of blood glucose (BG), serum creatinine (Scr), blood urea nitrogen (BUN), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and interleukin-1β (IL-1β). Nevertheless, resveratrol treatment did not effectively decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, more remarkable antioxidant and hypoglycemic effects were observed in type 2 diabetic nephropathy rather than in type 1 diabetic nephropathy based on subgroup analysis. In this meta-analysis, resveratrol can exert its antioxidant activities by reducing the levels of MDA and recovering the activities of SOD, CAT, GSH, and GPx. With regard to pro-inflammatory cytokines, resveratrol had a positive effect on the reduction of IL-1β. However, the analysis indicated that resveratrol had no effect on IL-6 and TNF-α levels, probably because of the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatory properties of resveratrol, but its relationship with the levels of some inflammatory cytokines such as IL-6 and TNF-α in animals with diabetic nephropathy needs further elucidation.
PubMed: 35355720
DOI: 10.3389/fphar.2022.841818 -
Computational Intelligence and... 2022Long noncoding RNA (lncRNA) is involved in the occurrence and development of diabetic kidney disease (DKD). It is necessary to identify the expression of lncRNA from DKD... (Review)
Review
BACKGROUND
Long noncoding RNA (lncRNA) is involved in the occurrence and development of diabetic kidney disease (DKD). It is necessary to identify the expression of lncRNA from DKD patients through systematic reviews, and then carry out silico analyses to recognize the dysregulated lncRNA and their associated pathways.
METHODS
The study searched Pubmed, Embase, Cochrane Library, WanFang, VIP, CNKI, and CBM to find lncRNA studies on DKD published before March 1, 2021. Systematic review of the literature on this topic was conducted to determine the expression of lncRNA in DKD and non-DKD controls. For the dysregulated lncRNA in DKD patients, silico analysis was performed, and lncRNA2Target v2.0 and starBase were used to search for potential target genes of lncRNA. The Encyclopedia of Genomics (KEGG) pathway enrichment analysis was performed to better identify dysregulated lncRNAs in DKD and determine the associated signal pathways.
RESULTS
According to the inclusion and exclusion criteria, 28 publications meeting the eligibility criteria were included in the systematic evaluation. A total of 3,394 patients were enrolled in this study, including 1,238 patients in DKD group, and 1,223 diabetic patients, and 933 healthy adults in control group. Compared with the control, there were eight lncRNA disorders in DKD patients (MALAT1, GAS5, MIAT, CASC2, NEAT1, NR_033515, ARAP1-AS2, and ARAP1-AS1). In addition, five lncRNAs (MALAT1, GAS5, MIAT, CASC2, and NEAT1) participated in disease-related signal pathways, indicating their role in DKD. . This study showed that there were eight lncRNAs in DKD that were persistently dysregulated, especially five lncRNAs which were closely related to the disease. Although systematic review included 28 studies that analyzed the expression of lncRNA in DKD-related tissues, the potential of these dysregulated lncRNAs as biomarkers or therapeutic targets for DKD remains to be further explored. Trial registration. PROSPERO (CRD42021248634).
Topics: Adult; Biomarkers; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Male; RNA, Long Noncoding; Signal Transduction
PubMed: 35528328
DOI: 10.1155/2022/8400106 -
Phytomedicine : International Journal... Jan 2023The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic benefits of Niaoduqing granules (NDQG) in kidney diseases has been comprehensively studied, but its adverse drug reactions remain unexplored.
OBJECTIVE
To evaluate the safety of NDQG in kidney disease treatment.
METHODS
The literature was searched in Embase, Medline via PubMed, Cochrane Library database, Wanfang database, Chinese National Knowledge Infrastructure, SinoMed, and Chinese VIP Database from inception to January 15, 2022, for randomized controlled trials (RCTs) and observational studies. The ClinicalTrials.gov website was searched for ongoing trials. The frequency and characteristics of adverse drug reactions (ADRs) were the primary and secondary outcomes, respectively. Subgroup analysis were conducted to explore the effects of clinical trial types, different kidney diseases, drug combinations and dosage on the safety of NDQG.
RESULTS
This review included 132 trials comprising 115 RCTs and 17 cohort studies. Additionally, 118 studies reported ADR rates with complete data, including 10381 participants. Regarding ADR frequency, no significant difference was observed between NDQG (7.26%) and control (8.39%) groups (RR = 0.890, 95% confidence interval (CI): 0.788-1.007); with no heterogeneity among the studies (I = 0.0%, P = 0.958). ADR frequency in patients with chronic kidney disease (65 trials, n = 5823) was significantly lower in the NDQG treatment group than in the control group (RR = 0.810, 95% CI: 0.67-0.969, I = 0.0%, P = 0.993); however, for patients with diabetic nephropathy there was no difference between both groups (26 trials, n = 2166, RR = 1.077, 95% CI: 0.802-1.446, I = 0.0%, P = 0.611). Similarly, the incidence of ADR in patients on dialysis and patients with pyelonephritis and nephrotic syndrome was the same for both groups, with 95% CI overlapping the line. For different interventions, including NDQG monotherapy or its combination with other commonly used drugs (including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin drugs, and compound α-keto acid) or dialysis, the incidence of ADR showed no significant difference between the experimental and control arms. The ADR in the NDQG group primarily affected the gastrointestinal system (64.74%), central and peripheral nervous system (9.07%), whole body (5.79%), and skin and appendages (4.53%). The most common clinical manifestations were diarrhea, nausea, and vomiting.
CONCLUSIONS
Our meta-analysis showed that compared with supportive therapy, the incidence of ADR was similar when NDQG was added. However, current evidence is not definitive and more well-designed and conducted RCTs are warranted to definitively establish the reliable evidence.
PROTOCOL REGISTRATION NUMBER
PROSPERO CRD 42018104227.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Renal Insufficiency, Chronic; Nephrotic Syndrome; Skin; Drug-Related Side Effects and Adverse Reactions
PubMed: 36610168
DOI: 10.1016/j.phymed.2022.154535