Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) Among Patients with Type 2 Diabetes Mellitus (T2DM) and Advanced CKD and ESKD: A Systematic Review and Meta-Analysis
ABSTRACT Background Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. Methods A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Results Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12 months (interquartile range 6–23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD −0.07 ml/min/1.73 m2 (95% CI −0.64–0.50)] or creatinine [SMD −0.08 mg/dl (95% CI −0.44–0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD −0.47 (95% CI −0.77 to −0.18)] and haemoglobin A1c levels [MD −0.85% (95% CI −1.41 to −0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD −0.43 ng/ml (95% CI −0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). Conclusions GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.
Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis
Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies—of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of −1.2%; 95% CI −2.0, −0.4) and pro-BNP (SMD −335.9 pmol/L; 95% CI −438.9, −232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD −1.1 mg/dL; 95% CI −1.8, −0.3) and increased weight loss (SMD −2.2 kg; 95% CI −2.9, −1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.
Distinct clinical profiles and post-transplant outcomes among kidney transplant recipients with lower education levels: uncovering patterns through machine learning clustering
AbstractBackgroundWe aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach.MethodsWe performed consensus cluster analysis on 11 615 deceased donor kidney transplant patients with CIT exceeding 24 h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post‐transplant outcomes were compared.ResultsConsensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non‐diabetic patients who received kidney transplants from young, non‐hypertensive, non‐ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42% vs. 29%), and lower 1‐year patient (95% vs. 98%) and death‐censored (95% vs. 97%) graft survival compared to Cluster 1.ConclusionsUnsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.
AI-Powered Renal Diet Support: Performance of ChatGPT, Bard AI, and Bing Chat
Patients with chronic kidney disease (CKD) necessitate specialized renal diets to prevent complications such as hyperkalemia and hyperphosphatemia. A comprehensive assessment of food components is pivotal, yet burdensome for healthcare providers. With evolving artificial intelligence (AI) technology, models such as ChatGPT, Bard AI, and Bing Chat can be instrumental in educating patients and assisting professionals. To gauge the efficacy of different AI models in discerning potassium and phosphorus content in foods, four AI models—ChatGPT 3.5, ChatGPT 4, Bard AI, and Bing Chat—were evaluated. A total of 240 food items, curated from the Mayo Clinic Renal Diet Handbook for CKD patients, were input into each model. These items were characterized by their potassium (149 items) and phosphorus (91 items) content. Each model was tasked to categorize the items into high or low potassium and high phosphorus content. The results were juxtaposed with the Mayo Clinic Renal Diet Handbook’s recommendations. The concordance between repeated sessions was also evaluated to assess model consistency. Among the models tested, ChatGPT 4 displayed superior performance in identifying potassium content, correctly classifying 81% of the foods. It accurately discerned 60% of low potassium and 99% of high potassium foods. In comparison, ChatGPT 3.5 exhibited a 66% accuracy rate. Bard AI and Bing Chat models had an accuracy rate of 79% and 81%, respectively. Regarding phosphorus content, Bard AI stood out with a flawless 100% accuracy rate. ChatGPT 3.5 and Bing Chat recognized 85% and 89% of the high phosphorus foods correctly, while ChatGPT 4 registered a 77% accuracy rate. Emerging AI models manifest a diverse range of accuracy in discerning potassium and phosphorus content in foods suitable for CKD patients. ChatGPT 4, in particular, showed a marked improvement over its predecessor, especially in detecting potassium content. The Bard AI model exhibited exceptional precision for phosphorus identification. This study underscores the potential of AI models as efficient tools in renal dietary planning, though refinements are warranted for optimal utility.