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Acta Diabetologica Mar 2023The overall effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate... (Meta-Analysis)
Meta-Analysis Review
Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.
AIMS
The overall effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR), 15-30 ml/min per 1.73 m) remain unclear, and we thus conducted a systematic review and meta-analysis to evaluate the effects of SGLT2 inhibitors on kidney, cardiovascular (CV), and safety outcomes in patients with advanced CKD.
METHODS
The Medline, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) published up to March 3, 2022, and reporting effects of SGLT2 inhibitors on kidney, CV, or safety outcomes in patients with advanced CKD.
RESULTS
From 2675 records, six RCTs with 2167 participants were included in the quantitative analyses. In patients with advanced CKD, SGLT2 inhibitors reduced the risk of the primary kidney outcome (a composite of worsening kidney function, end-stage kidney disease (ESKD), or kidney death) by 23% (RR 0.77, 95% CI 0.61-0.98, p = 0.04, I = 0 for the heterogeneity) and slowed the annual decline in eGFR slope, with the difference between SGLT2 inhibitor group and placebo group being 1.24 mL/min/1.73m per year (95% CI 0.06-2.42, p = 0.04). SGLT2 inhibitors were also associated with a decreased risk of primary CV outcome (a composite of CV death or hospitalization for heart failure) (HR 0.71, 95% CI 0.53-0.96, p = 0.03, I = 0 for the heterogeneity) and with similar risks of adverse events (such as acute kidney injury, fracture, amputation, and urinary tract infection).
CONCLUSIONS
Among patients with advanced CKD, SGLT2 inhibitors reduced the risks of primary kidney and CV outcomes and attenuated the progressive decrease in eGFR compared with placebo, with no evidence of additional safety concerns. These observed benefits may support continuing the use of SGLT2 inhibitors in patients with advanced CKD before initiating maintenance dialysis or kidney transplantation. Future large-scale RCTs are needed to confirm the robustness of these results.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Kidney; Symporters; Glucose; Sodium; Diabetes Mellitus, Type 2
PubMed: 36316605
DOI: 10.1007/s00592-022-01989-7 -
Tremor and Other Hyperkinetic Movements... 2023The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs... (Review)
Review
OBJECTIVES
The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.
MATERIALS AND METHODS
We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.
RESULTS
Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion.
CONCLUSION
This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.
Topics: Humans; Child; Gabapentin; Restless Legs Syndrome; Pregabalin; Quality of Life; Dopamine Agents; Renal Insufficiency, Chronic; Iron
PubMed: 37008995
DOI: 10.5334/tohm.752 -
American Journal of Kidney Diseases :... Nov 2021To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the relative efficacy and safety of different oral anticoagulant agents (OACs) for patients with atrial fibrillation (AF) and chronic kidney disease (CKD).
STUDY DESIGN
Systematic review and pairwise and Bayesian network meta-analysis.
SETTING & STUDY POPULATIONS
Adult patients with AF and CKD stages 3-5D who received OACs.
SELECTION CRITERIA FOR STUDIES
Randomized controlled trials (RCTs) and observational studies that reported the efficacy and safety outcomes of subgroups with a glomerular filtration rate (GFR)<60mL/min.
DATA EXTRACTION
Two reviewers independently abstracted data, assessed study quality, and rated the strength of evidence (SOE).
ANALYTICAL APPROACH
Random-effects models using restricted maximum-likelihood methods were fit for the pairwise meta-analyses as well as a network meta-analysis within a Bayesian framework.
RESULTS
Pairwise meta-analysis including 8 RCTs and 46 observational studies showed that direct OACs (DOACs) were superior to warfarin in preventing thromboembolic events (hazard ratio [HR], 0.86 [95% CI, 0.78-0.95]), without heterogeneity (I=10.5%), and in reducing the risk of bleeding events (HR, 0.81 [95% CI, 0.66-0.99]), with substantial heterogeneity (I=69.8%), in patients with AF and a GFR of 15-60mL/min. Bayesian network meta-analysis including 8 RCTs showed that dose-adjusted apixaban and a 15-mg dose of edoxaban were superior to the other OAC regimens in reducing bleeding events. Dose-adjusted apixaban was more effective than edoxaban in preventing thromboembolic events for patients with AF and GFR in the range of 25-50 or 30-50mL/min. In dialysis recipients with AF, the use of OACs increased the risk of bleeding events by 28% (HR, 1.28 [95% CI, 1.03-1.60]) without significant beneficial effects versus not using anticoagulants.
LIMITATIONS
Low SOE and heterogeneity in most comparisons.
CONCLUSIONS
This study suggests that DOACs are superior to warfarin for the prevention of thromboembolic events and reduction in bleeding risk in patients with AF and mild to moderate kidney disease. However, the low SOE limits the conclusions that can be drawn about the preferred DOAC. Notably, the use of OACs may increase bleeding risk without significant benefits in dialysis recipients with AF.
REGISTRATION
Registered at PROSPERO with identification number CRD42018090896.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Network Meta-Analysis; Renal Insufficiency, Chronic; Stroke
PubMed: 33872690
DOI: 10.1053/j.ajkd.2021.02.328 -
The Cochrane Database of Systematic... Feb 2023Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014.
OBJECTIVES
To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD.
SEARCH METHODS
In this update, we searched the Cochrane Kidney and Transplant Register of Studies up to 29 April 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, a biosimilar epoetin or a biosimilar darbepoetin alfa) with another ESA, placebo or no treatment in adults with CKD were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two independent authors screened the search results and extracted data. Data synthesis was performed using random-effects pairwise meta-analysis (expressed as odds ratios (OR) and their 95% confidence intervals (CI)) and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore sources of heterogeneity or inconsistency. We assessed certainty in treatment estimates for the primary outcomes (preventing blood transfusions and death (any cause)) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Sixty-two new studies (9237 participants) were included in this update, so the review now includes 117 studies with 25,237 participants. Most studies were at high or unclear risk of bias in most methodological domains. Overall, results remain similar in this update compared to our previous review in 2014. For preventing blood transfusion, epoetin alfa (OR 0.28, 95% CI 0.13 to 0.61; low certainty evidence) and epoetin beta (OR 0.19, 95% CI 0.08 to 0.47; low certainty evidence) may be superior to placebo, and darbepoetin alfa was probably superior to placebo (OR 0.27, 95% CI 0.11 to 0.67; moderate certainty evidence). Methoxy polyethylene glycol-epoetin beta (OR 0.33, 95% CI 0.11 to 1.02; very low certainty evidence), a biosimilar epoetin (OR 0.34, 95% CI 0.11 to 1.03; very low certainty evidence) and a biosimilar darbepoetin alfa (OR 0.37, 95% CI 0.07 to 1.91; very low certainty evidence) had uncertain effects on preventing blood transfusion compared to placebo. The comparative effects of ESAs compared with another ESA on preventing blood transfusions were uncertain, in low to very low certainty evidence. Effects on death (any cause) were uncertain for epoetin alfa (OR 0.79, 95% CI 0.51 to 1.22; low certainty evidence), epoetin beta (OR 0.69, 95% CI 0.40 to 1.20; low certainty evidence), methoxy polyethylene glycol-epoetin beta (OR 1.07, 95% CI 0.67 to 1.71; very low certainty evidence), a biosimilar epoetin (OR 0.80, 95% CI 0.47 to 1.36; low certainty evidence) and a biosimilar darbepoetin alfa (OR 1.63, 95% CI 0.51 to 5.23; very low certainty evidence) compared to placebo. There was probably no difference between darbepoetin alfa and placebo on the odds of death (any cause) (OR 0.99, 95% CI 0.81 to 1.21; moderate certainty evidence). The comparative effects of ESAs compared with another ESA on death (any cause) were uncertain in low to very low certainty evidence. Epoetin beta probably increased the odds of hypertension when compared to placebo (OR 2.17, 95% CI 1.17 to 4.00; moderate certainty evidence). Compared to placebo, epoetin alfa (OR 2.10, 95% CI 1.22 to 3.59; very low certainty evidence), darbepoetin alfa (OR 1.88, 95% CI 1.12 to 3.14; low certainty evidence) and methoxy polyethylene glycol-epoetin beta (OR 1.98, 95% CI 1.05 to 3.74; low certainty evidence) may increase the odds of hypertension, but a biosimilar epoetin (OR 1.88, 95% CI 0.96 to 3.67; low certainty evidence) and biosimilar darbepoetin alfa (OR 1.98, 95% CI 0.84 to 4.66; low certainty evidence) had uncertain effects on hypertension. The comparative effects of all ESAs compared with another ESA, placebo or no treatment on cardiovascular death, myocardial infarction, stroke, vascular access thrombosis, kidney failure, and breathlessness were uncertain. Network analysis for fatigue was not possible due to sparse data. AUTHORS' CONCLUSIONS: The comparative effects of different ESAs on blood transfusions, death (any cause and cardiovascular), major cardiovascular events, myocardial infarction, stroke, vascular access thrombosis, kidney failure, fatigue and breathlessness were uncertain.
Topics: Adult; Humans; Hematinics; Epoetin Alfa; Darbepoetin alfa; Biosimilar Pharmaceuticals; Network Meta-Analysis; Erythropoiesis; Anemia; Renal Insufficiency, Chronic; Hypertension; Thrombosis; Dyspnea; Myocardial Infarction
PubMed: 36791280
DOI: 10.1002/14651858.CD010590.pub3 -
Cardiovascular Diabetology May 2021Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD.
METHODS
MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model.
RESULTS
Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70-0.96), embolic stroke (RR 0.32, 95% CI 0.12-0.85), AF/AFL (RR 0.82, 95% CI 0.71-0.95), and VT (RR 0.73, 95% CI 0.53-0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58-1.17) and cardiac arrest (RR 0.83, 95% CI 0.61-1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used.
CONCLUSIONS
SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.
Topics: Aged; Arrhythmias, Cardiac; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 33962654
DOI: 10.1186/s12933-021-01293-8 -
European Journal of Pharmacology Oct 2020Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients... (Meta-Analysis)
Meta-Analysis
Sacubitril/valsartan (LCZ696) is recommended for ejection fraction reduction in heart failure. However, studies comparing the effects of sacubitril/valsartan in patients with heart failure and chronic kidney disease (CKD) with the inhibitor of renal angiotensin system (RAS) are limited. To further demonstrate the benefits of sacubitril/valsartan in patients with both heart failure and CKD, a meta-analysis of randomized controlled trials (RCTs) was conducted. The Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov were searched for RCTs. A total of 3460 individuals with heart failure and CKD were included in this meta-analysis. Sacubitril/valsartan was compared with irbesartan, valsartan and enalapril. It was found that sacubitril/valsartan significantly increased estimated glomerular filtration rate [eGFR, MD = 1.90, 95% CI (0.30, 3.50), P = 0.02]. However, sacubitril/valsartan had no difference in urinary albumin/creatinine ratio [UACR, MD = -0.30, 95% CI (-1.38, 0.78), P = 0.59] compared to the control group. Sacubitril/valsartan showed dramatically decrease in systolic blood pressure [SBP, MD = -4.39, 95% CI (-6.11, -2.68), P < 0.001], diastolic blood pressure [DBP, MD = -2.69, 95% CI (-4.04, -1.35), P < 0.001], and N-terminal prohormone brain natriuretic peptide [NT-proBNP, MD = -45.34, 95% CI (-46.63, -44.06), P < 0.001]. There was no significant difference in the incidence of adverse reactions between sacubitril/valsartan and the control group. Compared with the RAS inhibitor, sacubitril/valsartan significantly increased eGFR and decreased BP and NT-proBNP, which indicates that it might have cardiovascular and renal benefits in patients with heart failure and CKD.
Topics: Aged; Aged, 80 and over; Aminobutyrates; Angiotensin II Type 1 Receptor Blockers; Biphenyl Compounds; Drug Combinations; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Neprilysin; Protease Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Stroke Volume; Treatment Outcome; Valsartan
PubMed: 32739172
DOI: 10.1016/j.ejphar.2020.173444 -
European Journal of Pharmacology Sep 2022Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and sodium zirconium cyclosilicate (SZC), are emerging medications for the treatment of hyperkalemia with chronic kidney disease (CKD). However, which might be the best alternative for patients with chronic kidney disease and hyperkalemia remains disputed.
METHODS
We performed this systematic review and network meta-analysis with the Bayesian approach to conduct direct and indirect comparisons among potassium binders regarding their efficacy and safety. The surface under the cumulative ranking curve analysis (SUCRA) was used to calculate the best intervention for each outcome.
RESULTS
All four potassium binders had a promising effect regarding potassium reduction. SPS had favorable efficacy and safety for short-term use (MD: -0.94; 95% CIs: -1.4 to -0.48; SUCRA = 94.69%), but long-term treatment required strict dose control and assessment of gastrointestinal conditions. CPS had a positive effect on reducing potassium, and could especially maintain the serum potassium concentration in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Patiromer might reduce all-cause mortality in CKD patients with hyperkalemia and have a positive effect on potassium-lowering, though it had significant gastrointestinal adverse effects. SZC had a potassium-lowering effect in both the short-term and long-term, and can be a promising long-term treatment for the hyperkalemia in CKD patients, especially in combination with RAASi.
CONCLUSION
These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.
Topics: Bayes Theorem; Humans; Hyperkalemia; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 35964658
DOI: 10.1016/j.ejphar.2022.175174 -
Clinical Nutrition (Edinburgh, Scotland) May 2022Sarcopenia is a risk factor for adverse outcomes in older adults, but this has yet to be confirmed in chronic kidney disease (CKD). We conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Sarcopenia is a risk factor for adverse outcomes in older adults, but this has yet to be confirmed in chronic kidney disease (CKD). We conducted a systematic review to investigate the association between sarcopenia and its traits with mortality, hospitalization, and end-stage kidney disease (ESKD) progression in CKD patients.
METHODS
Five electronic databases were searched, including MEDLINE and Embase. Observational cohort studies with CKD patients were included. The sarcopenia traits assessed were low muscle strength, low muscle mass, and low physical performance, as well as diagnosed sarcopenia (combined low muscle mass and low strength/performance). Hazard ratios (HR), risk ratios (RR), odds ratios (OR), and 95% confidence intervals (CI) were pooled using random-effect meta-analyses.
RESULTS
From a total of 4922 screened studies, 50 (72,347 patients) were included in the review and 38 (59,070 patients) in the meta-analyses. Most of the included studies were in dialysis patients (n = 36, 72%). Pooled analyses showed that low muscle strength (15 studies; HR:1.99; 95%CI:1.65 to 2.41; I:45%), low muscle mass (20 studies; HR:1.51; 95%CI:1.36 to 1.68; I:26%) and low physical performance (five studies; HR:2.09; 95%CI:1.68 to 2.59; I:0%) were associated with increased mortality risk in CKD patients. Diagnosed sarcopenia was also associated with the mortality risk in dialysis patients (eight studies; HR:1.87; 95%CI:1.35 to 2.59; I:40%). On the other hand, it was uncertain whether low muscle mass was associated with hospitalization (two studies in dialysis patients; RR:1.81; 95% CI:0.78 to 4.22; I:59%). Further, limited ESKD progression measures prevented meta-analysis for this outcome.
CONCLUSIONS
Low muscle strength, low muscle mass, and low physical performance were associated with higher mortality in CKD patients. In dialysis patients, diagnosed sarcopenia also represented higher mortality risk. Evidence to conclude associations with hospitalization and ESKD progression is currently lacking.
PROSPERO REGISTRATION
CRD42020192198.
Topics: Aged; Female; Humans; Kidney Failure, Chronic; Male; Muscle Strength; Renal Dialysis; Renal Insufficiency, Chronic; Sarcopenia
PubMed: 35430544
DOI: 10.1016/j.clnu.2022.03.025 -
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