Yeoungjee Cho

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.

Haemodialysis (HD) is the commonest form of kidney replacement therapy in the world, accounting for approximately 69% of all kidney replacement therapy and 89% of all dialysis. Over the last six decades since the inception of HD, dialysis technology and patient access to the therapy have advanced considerably, particularly in high-income countries. However, HD availability, accessibility, cost and outcomes vary widely across the world and, overall, the rates of impaired quality of life, morbidity and mortality are high. Cardiovascular disease affects more than two-thirds of people receiving HD, is the major cause of morbidity and accounts for almost 50% of mortality. In addition, patients on HD have high symptom loads and are often under considerable financial strain. Despite the many advances in HD technology and delivery systems that have been achieved since the treatment was first developed, poor outcomes among patients receiving HD remain a major public health concern. Understanding the epidemiology of HD outcomes, why they might vary across different populations and how they might be improved is therefore crucial, although this goal is hampered by the considerable heterogeneity in the monitoring and reporting of these outcomes across settings. This Review examines the epidemiology of haemodialysis outcomes — clinical, patient-reported and surrogate outcomes — across world regions and populations, including vulnerable individuals. The authors also discuss the current status of monitoring and reporting of haemodialysis outcomes and potential strategies for improvement.

BACKGROUND: Since 2015, the International Society of Nephrology (ISN) Global Kidney Health Atlas (ISN-GKHA) has spearheaded multinational efforts to understand the status and capacity of countries to provide optimal kidney care, particularly in low-resource settings. In this iteration of the ISN-GKHA, we sought to extend previous findings by assessing availability, accessibility, quality, and affordability of medicines, kidney replacement therapy (KRT), and conservative kidney management (CKM). METHODS: A consistent approach was used to obtain country-level data on kidney care capacity during three phases of data collection in 2016, 2018, and 2022. The current report includes a detailed literature review of published reports, databases, and registries to obtain information on the burden of chronic kidney disease and estimate the incidence and prevalence of treated kidney failure. Findings were triangulated with data from a multinational survey of opinion leaders based on the WHO's building blocks for health systems (ie, health financing, service delivery, access to essential medicines and health technology, health information systems, workforce, and governance). Country-level data were stratified by the ISN geographical regions and World Bank income groups and reported as counts and percentages, with global, regional, and income level estimates presented as medians with interquartile ranges. FINDINGS: The literature review used information on prevalence of chronic kidney disease from 161 countries. The global median prevalence of chronic kidney disease was 9·5% (IQR 5·9-11·7) with the highest prevalence in Eastern and Central Europe (12·8%, 11·9-14·1). For the survey analysis, responses received covered 167 (87%) of 191 countries, representing 97·4% (7·700 billion of 7·903 billion) of the world population. Chronic haemodialysis was available in 162 (98%) of 165 countries, chronic peritoneal dialysis in 130 (79%), and kidney transplantation in 116 (70%). However, 121 (74%) of 164 countries were able to provide KRT to more than 50% of people with kidney failure. Children did not have access to haemodialysis in 12 (19%) of 62 countries, peritoneal dialysis in three (6%) countries, or kidney transplantation in three (6%) countries. CKM (non-dialysis management of people with kidney failure chosen through shared decision making) was available in 87 (53%) of 165 countries. The annual median costs of KRT were: US$19 380 per person for haemodialysis, $18 959 for peritoneal dialysis, and $26 903 for the first year of kidney transplantation. Overall, 74 (45%) of 166 countries allocated public funding to provide free haemodialysis at the point of delivery; use of this funding scheme increased with country income level. The median global prevalence of nephrologists was 11·8 per million population (IQR 1·8-24·8) with an 80-fold difference between low-income and high-income countries. Differing degrees of health workforce shortages were reported across regions and country income levels. A quarter of countries had a national chronic kidney disease-specific strategy (41 [25%] of 162) and chronic kidney disease was recognised as a health priority in 78 (48%) of 162 countries. INTERPRETATION: This study provides new information about the global burden of kidney disease and its treatment. Countries in low-resource settings have substantially diminished capacity for kidney care delivery. These findings have major policy implications for achieving equitable access to kidney care. FUNDING: International Society of Nephrology.

IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. RESULTS: A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%]). CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.