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.

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Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5.
Propensity score-matched cohort study.
2 nationwide US claims databases, Medicare and Optum\'s deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n = 5,720).
Warfarin, rivaroxaban, or apixaban.
Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding.
Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders.
Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings.
Few ischemic stroke events, potential residual confounding.
In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population.
Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are hypoglycemic agents, have been shown to be cardioprotective through a variety of mechanisms, and the effect of lowering uric acid (UA) levels may be one of the mechanisms. In the present retrospective study, we investigated the changes in serum UA levels in patients with chronic kidney disease (CKD) treated with SGLT2 inhibitors. Methods We included 31 patients with CKD who were newly started on dapagliflozin for renal protection and evaluated trends in various parameters, including serum UA levels and UA excretion from urine. Results The patients\' median age was 71 years old, 20 patients were men, 7 patients had diabetes, and the median estimated glomerular filtration rate was 33.9 mL/min/1.73 m2 (CKD stage 3: 21 cases, stage 4: 10 cases). The differences in UA and fractional excretion of UA after three weeks and three months of prescription showed significantly decreased UA values and an increased fractional excretion of UA. Conclusion Our findings suggest that dapagliflozin can lower serum UA levels via increased UA excretion, even in patients with advanced CKD.

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Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD).
We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m2) were recorded per year. The proportion of trials with advanced CKD was logtransformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson\'s correlation and univariate linear regression.
A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year.
In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased.

Patients with advanced chronic kidney disease (CKD) have been reported to experience profound psychosocial distress. Other work has established that patients with CKD from marginalized populations (including individuals who on the basis of race often face racism and related discrimination, termed \"racialization\") experience health care inequities. Given limited information on the intersection of these 2 phenomena, we assessed the association of psychosocial distress with racialized status and immigrant status in Canadians with advanced CKD.
Secondary analysis of cross-sectional data.
536 patients with advanced CKD (estimated glomerular filtration rate<30mL/min/1.73m2, with or without kidney replacement therapy) from multiple clinical centers in Toronto.
Racialized status (individuals who identify as Asian or as African, Caribbean, or Black Canadian), immigrant status, and combined immigrant-racialized status.
Psychosocial distress, defined as the presence of depression, anxiety, or social difficulties (ie, a score of≥10 points on the Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, or Social Distress 16 scales, respectively).
The independent associations of racialized status and immigrant status with psychosocial distress, depression, anxiety, and social difficulties were examined using univariable- and multivariable-adjusted logistic regression.
Mean age of the 536 participants was 57±16 (SD) years, 62% were male, and 45% were immigrants. Of the sample, 58% were White, 22% were African, Caribbean, or Black Canadian, and 20% were Asian. Psychosocial distress was present in 36% of participants (depression in 19%, anxiety in 12%, and social difficulties in 31%). To assess the combined impact of racialized and immigrant status, we created a variable with mutually exclusive categories: White nonimmigrant, racialized nonimmigrant, White immigrant, and racialized immigrant participants. In our final multivariable-adjusted model, compared with White nonimmigrant participants, racialized immigrant participants were more likely to have psychosocial distress (OR, 2.96 [95% CI, 1.81-4.81]), depression (OR, 1.87 [95% CI, 1.05-3.34]), and social difficulties (OR, 3.36 [95% CI, 2.03-5.57]). Overall similar associations were seen for racialized nonimmigrants and for White immigrants.
Convenience sample; small subgroups; combined exposure variable grouping Asian and African, Caribbean, and Black participants together; lack of data about mechanisms.
Both racialized and immigrant status based on self-report of demographic characteristics were associated with psychosocial distress among patients with advanced CKD. These patients may benefit from culturally competent psychosocial support.
Psychosocial distress is frequent in patients with advanced chronic kidney disease and impacts quality of life and clinical outcomes. Psychosocial distress may be especially scarring in people who are racialized (marginalized on account of their membership in a particular racial group) and/or who are immigrants. We assessed the association of psychosocial distress with racialized and immigrant status in Canadians with advanced chronic kidney disease. Among 536 participants from multiple medical centers in Toronto, we found that racialized and immigrant participants were more likely to have psychosocial distress, depression, and social difficulties compared with White nonimmigrant participants. This is likely related to the multiple intersectional challenges, including experience with racism and discrimination that racialized immigrant patients may face. Further studies are needed to elucidate the specific factors that contribute to more distress. The potential impact of culturally competent and safe support for these patients will also need to be studied.

The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and comorbidity is uncertain.
Multicenter, parallel group, randomized controlled trial.
Adults 55 years and older with estimated glomerular filtration rate (eGFR) of 15 to <45 mL/min/1.73 m2 enrolled from centers in Baltimore and Boston.
Twelve months of in-center supervised exercise training incorporating majority aerobic but also muscle strengthening activities or a group health education control intervention, randomly assigned in 1:1 ratio.
Primary outcomes were cardiorespiratory fitness and submaximal gait at 6 and 12 months quantified by peak oxygen consumption (Vo2peak) on graded exercise treadmill test and distance walked on the 6-minute walk test, respectively. Secondary outcomes were changes in lower extremity function, eGFR, albuminuria, glycemia, blood pressure, and body mass index.
Among 99 participants, the mean age was 68 years, 62% were African American, and the mean eGFR was 33 mL/min/1.73 m2; 59% had diabetes, and 29% had coronary artery disease. Among those randomized to exercise, 59% of exercise sessions were attended in the initial 6 months. Exercise was well tolerated without excess occurrence of adverse events. At 6 months, aerobic capacity was higher among exercise participants (17.9 ± 5.5 vs 15.9 ± 7.0 mL/kg/min, P = 0.03), but the differences were not sustained at 12 months. The 6-minute walk distance improved more in the exercise group (adjusted difference: 98 feet [P = 0.02; P = 0.03 for treatment-by-time interaction]). The exercise group had greater improvements on the Timed Up and Go Test (P = 0.04) but not the Short Physical Performance Battery (P = 0.8).
Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated.
Among adults aged ≥55 years with CKD stages 3b-4 and a high level of medical comorbidity, a 12-month program of in-center aerobic and resistance exercise training was safe and associated with improvements in physical functioning.
Government grants (National Institutes of Health).
Registered at ClinicalTrials.gov with study number NCT01462097.

Little is known about psychological issues in patients with chronic kidney disease (CKD) facing transition to kidney failure and the involvement of their family in decision-making about kidney replacement therapy (KRT). This study investigated patients\' experience of their illness, their views on KRT choice and their perception of the influence of their relatives.
We conducted a qualitative study nested in the CKD-REIN prospective cohort study which included non-dialysis CKD patients from 40 nationally representative nephrology clinics. Among 1555 patients who returned a self-administered questionnaire, we used purposive sampling to select 50 participants who underwent semi-structured phone interviews with a psychologist.
The patients\' mean age was 62.2 ± 12 years, 42% were women, and 68% had CKD stage 4-5. The analysis yielded four lexical classes: \"illness rhythm\", \"considering dialysis\", \"family and transplantation\", and \"disease, treatment choice and introspection\". When experiencing few or mild symptoms, patients tended to avoid thinking about CKD, for the prospect of dialysis was the most stressful part of their experience. Surprisingly, the importance of family appeared when they talked about transplantation decision-making, but not about choice of dialysis modality.
Cognitive avoidance seems common in patients with advanced CKD. Transplantation and dialysis decision-making appear to be two distinct processes, with different levels of family involvement. More research is needed to better understand the frequency and impact of cognitive avoidance on patients\' well-being and decision-making.