Dataset Information

Treatment of diabetic kidney disease. A network meta-analysis.

ABSTRACT:

Background

Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.

Methods

We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Results

Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.

Conclusions

As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.

SUBMITTER: Buttner F

PROVIDER: S-EPMC10621862 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Treatment of diabetic kidney disease. A network meta-analysis.

Büttner Fabian F Barbosa Clara Vollmer CV Lang Hannah H Tian Zhejia Z Melk Anette A Schmidt Bernhard M W BMW

PloS one 20231102 11

<h4>Background</h4>Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.<h4>Methods</h4>We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-e ...[more]

PMID: 37917640

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Project description:BackgroundAntihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease.MethodsMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed.ResultsA total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria.ConclusionsTrandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria for normotensive patients, while fosinopril+amlodipine appears to be the most efficacious intervention for reducing albuminuria for hypertensive patients. For practitioners opting for monotherapy, our SUCRA analysis supports the use of trandolapril and fosinopril in normotensive and hypertensive adult diabetic patients with microalbuminuria, respectively.

Project description:Objectives: To evaluate and compare the efficacy, safety, and cost of nine Chinese patent medicines (CPMs) combined with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in treating early diabetic kidney disease (DKD). Design: Systematic review and network meta-analysis. Data sources: PubMed, Embase, Cochrane Library, Web of Science, clinicaltrials.gov, SinoMed, Chinese Biomedicine, China National Knowledge Infrastructure, WanFang, and Chongqing VIP Information databases were comprehensively searched from the beginning to February 2022. Review Methods: Randomized controlled trials (RCTs) including Bailing capsule (BLC); Jinshuibao capsule (JSB); Huangkui capsule (HKC); Compound Xueshuantong capsule (CXC); uremic clearance granule (UCG); Shenyan Kangfu tablet (SYKFT); tripterygium glycosides (TG); Keluoxin capsule (KLX), and Shenshuaining tablet (SSNT) combined with ACEI/ARB for patients with early DKD were reviewed. Data Synthesis: Two reviewers independently screened articles, extracted data, and assessed the risk of bias. Risk ratios (RRs) and mean difference (MD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Using the surface under the cumulative ranking curve (SUCRA), we then ranked each therapeutic regime. Results: Ultimately, 160 RCTs involving 13,365 patients and nine CPMs were included. UCG showed significantly higher probabilities on urinary albumin excretion rate (UAER) when compared with ACEI/ARB group, with MD of -47 (95%CI) (-57, -37) and SUCRA 98.0%. The CXC group achieved a remarkable improvement in overall response rate (ORR) compared with ACEI/ARB (RR, 1.3, 95%CI (1.2, 1.5)) with SUCRA 91.9%. SSNT could be significantly superior to ACEI/ARB group in terms of serum creatinine (Scr) (-19 (-26, -12), SUCRA 99.3%) and adverse effects (AEs) (0.46 (0.17, 1.1), SUCRA 82.9%). BLC showed the greatest effectiveness on 24 h urinary total protein (24 h UTP) (-170 (-260, -83), SUCRA 78.5%) and triglyceride (Trig) (-0.89 (-1.2, -0.53), SUCRA 97.0%). From the cost-effectiveness analysis of CPMs in China, the cost of TG, SYKFT and CXC was 108, 600, and 648 RMB, respectively, per 3 months and were ranked in the top three. Conclusion: UCG and CXC might be the optimum selection for improving UAER and ORR, and SSNT could be significantly superior to ACEI/ARB group in terms of Scr and AEs. BLC shows the best curative effect on 24 h UTP and Trig. TG shows the highest cost-effectiveness among the nine CPMs.

Project description:Background Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined. Methods Studies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis. Results A total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD. Conclusions Gut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.

Project description:BackgroundDiabetic kidney disease (DKD) is the primary contributor to renal failure and poses a severe threat to human health. Accumulating studies demonstrated that competing endogenous RNA (ceRNA) network is involved in cuproptosis and DKD progression. However, the role of cuproptosis-associated ceRNA network and immune infiltration in DKD remains largely unclear. This study aimed to investigate the cuproptosis-related ceRNA regulation network and immune infiltration in DKD.MethodsThe rat model of DKD was induced by combining the nephrectomy of the left kidney, high-fat diet, and streptozotocin. Differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and DKD rats were obtained. DEGs were intersected with cuproptosis-related genes (CRGs) to obtain DE-CRGs. LncRNAs and miRNAs were predicted based on the DE-CRGs, and they were intersected with DEMs and DELs, respectively. Subsequently, a cuproptosis-associated lncRNA-miRNA-mRNA network was established in DKD. In addition, the relative proportion of 22 infiltrating immune cell types in each sample was calculated, and the relationship between hub DE-CRGs and immune cells was explored.ResultsIn total, there were 429 DEGs, 22 DEMs, and 48 DELs between CON and MOD groups. Then, 73 DE-CRGs were obtained, which were significantly enriched in 22 pathways, such as MAPK signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a core cuproptosis-related ceRNA network that included one lncRNA (USR0000B2476D), one miRNA (miR-34a-3p), and eight mRNAs (Mmp9, Pik3c3, Prom1, Snta1, Slc51b, Ntrk3, Snca, Egf) was established. In addition, 18 hub DE-CRGs were obtained. CIBERSORT algorithms showed that resting dendritic cells and resting NK cells were more infiltrated whereas regulatory T cells were less infiltrated in DKD rats than in normal rats. Spearman's correlation analysis revealed that hub DE-CRGs showed significant positive or negative correlations with naive B cells, regulatory T cells, resting NK cells, M0 macrophages, resting dendritic cells, and resting mast cells.ConclusionA ceRNA network was comprehensively constructed, and 18 hub DE-CRGs were obtained, which will provide novel insights into the pathologic mechanism elucidation and targeted therapy development of DKD.

Dataset Information

Treatment of diabetic kidney disease. A network meta-analysis.

Background

Methods

Results

Conclusions

Publications

Treatment of diabetic kidney disease. A network meta-analysis.

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