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PloS One 2023Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM).... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: A systematic review and meta-analysis.
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown a favorable effect on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM). However, their efficacy in patients with chronic kidney disease (CKD) with or without T2DM has not yet been analyzed.
OBJECTIVE
To assess the cardiovascular and renal effects of SGLT-2 inhibitors in patients with CKD with and without T2DM, including all CKD patients in the current literature.
METHODS
We searched MEDLINE, EMBASE, CENTRAL and Scopus for randomized controlled trials of SGLT-2 inhibitors that evaluated cardiovascular and kidney outcomes in patients with CKD, or trials in which these patients were a subgroup. We defined 2 primary outcomes: a composite of cardiovascular death or hospitalization for heart failure, and a composite renal outcome. For each outcome, we obtained overall hazard ratios with 95% confidence intervals by using a random effects model.
RESULTS
We included 14 randomized controlled trials. SGLT-2 inhibitors decreased the hazard for the primary cardiovascular outcome (HR 0.76; [95% CI 0.72-0.79]) and the primary renal outcome (HR 0.69; [95% CI 0.61-0.79]) in patients with CKD with or without T2DM. We did not find significant differences in the subgroup analyses according to diabetes status, baseline eGFR values or the type of SGLT-2 inhibitor used.
CONCLUSION
In patients with CKD, treatment with SGLT-2 inhibitors in addition to standard therapy conferred protection against cardiovascular and renal outcomes. Further research on patients with non-diabetic CKD should be done to confirm the utility of these medications in this population. (PROSPERO ID: CRD42021275012).
Topics: Humans; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Renal Insufficiency, Chronic; Heart Failure; Kidney; Glucose; Sodium; Cardiovascular Diseases; Randomized Controlled Trials as Topic
PubMed: 38019892
DOI: 10.1371/journal.pone.0295059 -
Diabetes Research and Clinical Practice Apr 2023To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials.
AIM
To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population.
METHODS
PubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601).
RESULTS
This network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61-0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06-1.62). Then MRAs (RR 0.77, 95%CI 0.68-0.88; MD 1.31, 95%CI 0.89-1.74), GLP-1RAs (RR 0.78, 95%CI 0.62-0.97; MD 0.75, 95%CI 0.46-1.05), and ERAs (RR 0.75, 95%CI 0.57-0.99; MD 0.7, 95%CI 0.3-1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57-0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55-0.97) and MRAs (RR 0.79, 95%CI 0.67-0.92). SGLT-2Is (RR 0.8, 95%CI 0.71-0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6-0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05-1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86-2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65-0.93) were in contrast.
CONCLUSIONS
SGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Network Meta-Analysis; Bayes Theorem; Hyperkalemia; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Kidney; Glucagon-Like Peptide-1 Receptor
PubMed: 36842477
DOI: 10.1016/j.diabres.2023.110592 -
BMJ (Clinical Research Ed.) Sep 2021To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes.
OBJECTIVES
To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes.
DESIGN
Systematic review and external validation.
DATA SOURCES
PubMed and Embase.
ELIGIBILITY CRITERIA
Studies describing the development of a model to predict the risk of nephropathy, applicable to people with type 2 diabetes.
METHODS
Screening, data extraction, and risk of bias assessment were done in duplicate. Eligible models were externally validated in the Hoorn Diabetes Care System (DCS) cohort (n=11 450) for the same outcomes for which they were developed. Risks of nephropathy were calculated and compared with observed risk over 2, 5, and 10 years of follow-up. Model performance was assessed based on intercept adjusted calibration and discrimination (Harrell's C statistic).
RESULTS
41 studies included in the systematic review reported 64 models, 46 of which were developed in a population with diabetes and 18 in the general population including diabetes as a predictor. The predicted outcomes included albuminuria, diabetic kidney disease, chronic kidney disease (general population), and end stage renal disease. The reported apparent discrimination of the 46 models varied considerably across the different predicted outcomes, from 0.60 (95% confidence interval 0.56 to 0.64) to 0.99 (not available) for the models developed in a diabetes population and from 0.59 (not available) to 0.96 (0.95 to 0.97) for the models developed in the general population. Calibration was reported in 31 of the 41 studies, and the models were generally well calibrated. 21 of the 64 retrieved models were externally validated in the Hoorn DCS cohort for predicting risk of albuminuria, diabetic kidney disease, and chronic kidney disease, with considerable variation in performance across prediction horizons and models. For all three outcomes, however, at least two models had C statistics >0.8, indicating excellent discrimination. In a secondary external validation in GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland), models developed for diabetic kidney disease outperformed those for chronic kidney disease. Models were generally well calibrated across all three prediction horizons.
CONCLUSIONS
This study identified multiple prediction models to predict albuminuria, diabetic kidney disease, chronic kidney disease, and end stage renal disease. In the external validation, discrimination and calibration for albuminuria, diabetic kidney disease, and chronic kidney disease varied considerably across prediction horizons and models. For each outcome, however, specific models showed good discrimination and calibration across the three prediction horizons, with clinically accessible predictors, making them applicable in a clinical setting.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020192831.
Topics: Aged; Albuminuria; Calibration; Clinical Decision Rules; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prognosis; Renal Insufficiency, Chronic; Reproducibility of Results; Risk Assessment; Risk Factors
PubMed: 34583929
DOI: 10.1136/bmj.n2134 -
Journal of the... 2019The effect of dual renin-angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of dual renin-angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis.
METHODS
A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events.
RESULTS
Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (=0.0006) in all individuals, and to 0.86 (=0.005) in patients with RD and to 0.91 (=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (=0.00001).
CONCLUSIONS
Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Hospitalization; Humans; Renal Insufficiency, Chronic
PubMed: 31814505
DOI: 10.1177/1470320319882656 -
Seminars in Dialysis Jan 2021Cardiac resynchronization therapy with or without a defibrillator (CRT(D)) and implantable cardioverter defibrillator (ICD) may reduce the risk of arrhythmia or heart... (Meta-Analysis)
Meta-Analysis Review
Cardiac resynchronization therapy with or without a defibrillator (CRT(D)) and implantable cardioverter defibrillator (ICD) may reduce the risk of arrhythmia or heart failure-specific mortality and improves the prognosis of patients with chronic kidney disease (CKD) or dialysis. The aim of this study was to perform a meta-analysis investigating the relationship between CRT(D)/ICD and renal insufficiency. Cochrane Library, Web of Science, Embase, and Pubmed were systematically searched from inception to 29 October 2019. We included studies that report all-cause mortality of patients with renal insufficiency who received CRT(D)/ICD therapy. Twenty-six studies (n = 119,263) were included, exploring the relationship between CRT(D)/ICD and renal insufficiency from two aspects: (1) Compared with ICD-only, CRT(D) was associated with lower risk of all-cause mortality in CKD patients (odds ratios (OR) = 0.67; 95% confidence interval (CI), 0.60 to 0.75). For non-primary prevention (secondary prevention or both), the analysis revealed a lower risk of all-cause mortality in the ICD group than in the no-ICD group (OR = 0.47; 95% CI, 0.40 to 0.55). (2) CKD increased all-cause mortality in comparison with control group (OR = 2.12; 95% CI, 1.85 to 2.44), and so did dialysis (OR = 2.53; 95% CI, 2.34 to 2.73). Furthermore, compared with CKD3 (eGFR: 30-59 ml/min/1.73 m ), CKD4/5 (eGFR <30 ml/min/1.73 m ) was observed to have a significantly higher risk of all-cause mortality (OR = 2.70; 95% CI, 1.93 to 3.80). This review shows a clear association between CRT(D)/ICD and renal insufficiency in the aspect of all-cause mortality, and may provide a reference for the clinical application of CRT(D)/ICD.
Topics: Cardiac Resynchronization Therapy; Defibrillators, Implantable; Heart Failure; Humans; Renal Dialysis; Renal Insufficiency; Risk Factors; Treatment Outcome
PubMed: 33296540
DOI: 10.1111/sdi.12937 -
Regenerative Medicine Dec 2022This study aims to compare the efficacy of tissue engineering for kidney reconstruction. We searched MEDLINE, EMBASE (May 2021), and reference lists of review... (Meta-Analysis)
Meta-Analysis
This study aims to compare the efficacy of tissue engineering for kidney reconstruction. We searched MEDLINE, EMBASE (May 2021), and reference lists of review articles. 19 articles matched our inclusion criteria. A range of natural, synthetic and hybrid scaffolds with or without incorporating cells/growth factors was investigated in 937 animals. More favorable results were observed with a combination of two or more biomaterials, addition of bioactive moieties, and cell seeding. Creatinine concentration, PAX2, collagen type-1, α-SMA, vimentin, IL-1, IL-6 and TNF-α gene expressions were significantly increased compared with native control. Tissue engineering can improve renal function and regeneration; however, further research could benefit from using hybrid scaffolds, stem cells and large animal models.
Topics: Animals; Tissue Engineering; Tissue Scaffolds; Vimentin; Creatinine; Interleukin-6; Tumor Necrosis Factor-alpha; Biocompatible Materials; Kidney; Collagen; Renal Insufficiency; Interleukin-1
PubMed: 36154467
DOI: 10.2217/rme-2022-0084 -
Ethiopian Journal of Health Sciences Sep 2020Anemia in patients with chronic kidney disease presents significant impacts on patients, the health-care system and financial resources. There is a significant variation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anemia in patients with chronic kidney disease presents significant impacts on patients, the health-care system and financial resources. There is a significant variation in the primary studies on risk factors of anemia in this patient population across the globe. Therefore, this study aimed to identify the risk factors of anemia among chronic kidney disease patients at the global level.
METHODS
PubMed, Scopus, African Journals Online, Web of Science and Google Scholar were searched and complemented by manual searches. A Funnel plot and Egger's regression test were used to determine publication bias. DerSimonian and Laird random-effects modes were applied to estimate pooled effect sizes, odds ratios, and 95% confidence interval across studies. Analysis was performed using STATA™ Version 14 software.
RESULT
A total of 28 studies with 24,008 study participants were included in this study. Female sex (AOR= 1.36; 95% CI 1.11, 1.67), stage 5 CKD (AOR = 13.66; 95% CI: 5.19, 35.92), body mass index ≥ 30 kg/m (AOR = 0.51; 95% CI: 0.29, 0.91), comorbidities (AOR = 2.90; 95% CI: 1.68, 5.0), proteinuria 3(AOR = 3.57; 95% CI: 1.03, 12.93), hypocalcemia (AOR=3.61, 95%CI: 1.56-8.36), and iron therapy (AOR: 0.59; 95% CI:0.31, 0.98) were significantly associated with anemia of chronic kidney disease.
CONCLUSION
Female sex, stage 5 CKD, body mass index ≥ 30 kg/m, comorbidity, and hypocalcemia were found to be significantly associated with anemia of chronic kidney disease. Therefore, situation-based interventions and country context-specific preventive strategies should be developed to reduce the risk factors of anemia in patients with chronic renal failure.
Topics: Anemia; Female; Humans; Kidney Failure, Chronic; Prevalence; Renal Insufficiency, Chronic; Risk Factors
PubMed: 33911845
DOI: 10.4314/ejhs.v30i5.23 -
Kidney International Feb 2015Deterioration in renal function has been described after endovascular repair of abdominal aortic aneurysms (EVRs). The etiology is multifactorial and represents an... (Meta-Analysis)
Meta-Analysis Review
Deterioration in renal function has been described after endovascular repair of abdominal aortic aneurysms (EVRs). The etiology is multifactorial and represents an important therapeutic target. A need exists to quantitatively summarize incidence and severity of renal dysfunction after EVR to allow better-informed attempts to preserve renal function and improve life expectancy. Here a systematic search was performed using Medline and Embase for renal function after EVR applying PRISMA statements. Univariate and multivariate random-effects meta-analyses were performed to estimate pooled postoperative changes in serum creatinine and creatinine clearance at four time points after EVR. Clinically relevant deterioration in renal function was also estimated at 1 year or more after EVR. Pooled probability of clinically relevant deterioration in renal function at 1 year or more was 18% (95% confidence interval of 14-23%, I2 of 82.5%). Serum creatinine increased after EVR by 0.05 mg/dl at 30 days/1 month, 0.09 mg/dl at 1 month to 1 year, and 0.11 mg/dl at 1 year or more (all significant). Creatinine clearance decreased after EVR by 5.65 ml/min at 1 month-1 year and by 6.58 ml/min at 1 year or more (both significant). Thus, renal dysfunction after EVR is common and merits attention.
Topics: Aortic Aneurysm, Abdominal; Creatinine; Endovascular Procedures; Humans; Kidney; Postoperative Complications; Renal Insufficiency; Time Factors
PubMed: 25140912
DOI: 10.1038/ki.2014.272 -
Journal of Nephrology Mar 2023Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast,... (Meta-Analysis)
Meta-Analysis Review
Revisiting maintenance immunosuppression in patients with renal transplant failure: early weaning of immunosuppression versus prolonged maintenance-systematic review and meta-analysis.
INTRODUCTION
Prolonged immunosuppression after dialysis start has been assumed to reduce sensitization, need for graft nephrectomy, and to favor re-transplantation. In contrast, immunosuppression is considered to increase the risk of mortality, infection, and malignancy. We aimed to assess the evidence regarding superiority of early or late withdrawal of maintenance immunosuppression post renal transplant failure.
METHODS
A literature search of the PubMed, WOS, Ovid, and Scopus databases was conducted. Combined relative risks, (RRs), mean differences, and 95% confidence intervals (CIs) were calculated by using a random-effect model.
RESULTS
Ten studies involving 1187 patients with kidney transplant failure were included. No difference could be detected between patients with early withdrawal of immunosuppressive drugs (≤ 3 months) or prolonged immunosuppressive treatment (> 3 months) regarding mortality (95% CI 0.91-2.28), panel reactive antibodies (PRAs) (95% CI - 0.75-30.10), re-transplantation rate (95% CI 0.55-1.35), infectious episodes (95% CI 0.67, 1.17), cancer (95% CI 0.26-1.54), and graft nephrectomy (95% CI 0.82-1.63). Similarly, no difference was found between immunosuppressive drug withdrawal over < 6 or ≥ 6 months regarding mortality (95% CI 0.16, 2.89), re-transplantation rate (95% CI 0.85-1.55), cancer (95% CI 0.37-1.63), and allograft nephrectomy (95% CI 0.87-4.33).
CONCLUSION
Prolonged maintenance immunosuppression post kidney transplant failure is not associated with increased risk of mortality, infection, or malignancy, or reduced risk of sensitization or allograft nephrectomy compared with early withdrawal.
Topics: Humans; Kidney Transplantation; Weaning; Immunosuppression Therapy; Immunosuppressive Agents; Immune Tolerance; Renal Insufficiency; Graft Rejection
PubMed: 36109426
DOI: 10.1007/s40620-022-01458-y -
BMJ Open Oct 2022To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. (Meta-Analysis)
Meta-Analysis
Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials.
OBJECTIVES
To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes.
METHODS
We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI.
RESULTS
We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion.
CONCLUSIONS
Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD.
PROSPERO REGISTRATION NUMBER
CRD42021239807.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36241355
DOI: 10.1136/bmjopen-2021-060655