Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants.

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85-0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

Cardiovascular and renal outcomes of initial combination therapy with glucose-lowering agents versus a stepwise approach in newly diagnosed or treatment-naïve type 2 diabetes: A systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of the initial combination therapy versus a stepwise approach in newly diagnosed type 2 diabetes (T2D) by conducting a systematic review and meta-analysis of observational cohort studies and randomized controlled trials (RCTs). METHODS: Studies were identified from MEDLINE, Embase, the Cochrane Library, and through search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Eight articles including four unique RCTs (n = 5527 participants) and one observational cohort study (n = 200) that compared initial combination therapy versus stepwise therapy were included. The RR for myocardial infarction comparing initial combination therapy versus stepwise therapy was 1.21 (95% CI 0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and glycated haemoglobin: mean differences -0.97 mmol/L (95% CI -1.41, -0.53) and -24.92 mmol/mol (95% CI -25.67, -24.27), respectively. Initial combination therapy versus stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition variables, neuropathy, retinopathy or adverse events. Single-study results showed that initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low. CONCLUSIONS: Except for improving cardiometabolic and glycaemic variables, a limited number of studies characterized by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D with the aim of preventing cardio-renal outcomes. Definitive RCTs are warranted.

Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis.

BACKGROUND AND AIMS: There is limited data on clinical outcomes in high risk groups such as patients with diabetes mellitus (DM) with atrial fibrillation (AF) on direct-acting oral anticoagulants (DOACs). Using a systematic review and meta-analysis of published studies, we aimed to determine the risk of stroke and other clinical outcomes in patients with AF on DOACs, with or without DM. METHODS: Observational cohort studies reporting clinical outcomes in patients with AF on DOACs, with or without DM were identified from MEDLINE, Embase, Web of Science, the Cochrane Library, and search of bibliographies to April 2020. Summary measures of effect were relative risks with 95% confidence intervals (CIs). RESULTS: Eight studies comprising of 4 observational cohorts (n = 76,260 participants) and 4 randomised controlled trials (RCTs) (n = 71,683 participants) were included. In RCTs, DOACs compared with warfarin reduced the risk of the composite outcome of stroke and systemic embolism, CVD death and intracranial bleeding in patients with DM: RRs (95% CIs) of 0.75 (0.62-0.90), 0.84 (0.72-0.97), and 0.57 (0.40-0.81) respectively. The corresponding estimates for patients without DM were 0.81 (0.68-0.96), 0.93 (0.80-1.08), and 0.47 (0.31-0.70) respectively. There was no evidence of interactions between DM status and effects of DOACs. The absolute reduction in clinical outcomes with DOACs compared to warfarin was greater in DM than without DM. Regardless of treatment strategy, interventional and observational evidence indicate that patients with DM had higher rates of stroke or systemic embolism, mortality and major bleeding compared to patients without DM. CONCLUSIONS: Patients with AF and DM have increased risk of vascular events, which is reduced with the use of DOACs. The use of DOACs should be considered as an option in reducing the risk of stroke in these populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020: CRD42020157196.