Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Propensity score-matched cohort study. SETTING & PARTICIPANTS: 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). EXPOSURES: Warfarin, rivaroxaban, or apixaban. OUTCOMES: Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. ANALYTICAL APPROACH: Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. RESULTS: 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. LIMITATIONS: Few ischemic stroke events, potential residual confounding. CONCLUSIONS: 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. PLAIN-LANGUAGE SUMMARY: 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.

Effect of Long-term Exercise Training on Physical Performance and Cardiorespiratory Function in Adults With CKD: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: The safety and efficacy of long-term exercise training in reducing physical functional loss in older adults with advanced CKD and comorbidity is uncertain. STUDY DESIGN: Multicenter, parallel group, randomized controlled trial. SETTINGS & PARTICIPANTS: 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. INTERVENTION: 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. OUTCOME: 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. RESULTS: 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). LIMITATIONS: Planned sample size was not reached. Loss to follow-up and dropout were greater than anticipated. CONCLUSIONS: 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. FUNDING: Government grants (National Institutes of Health). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01462097.

Psychosocial Distress in Patients With Advanced CKD by Racial Group and Immigrant Status: A Canadian Cross-sectional Study.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Secondary analysis of cross-sectional data. SETTING & PARTICIPANTS: 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. EXPOSURE: Racialized status (individuals who identify as Asian or as African, Caribbean, or Black Canadian), immigrant status, and combined immigrant-racialized status. OUTCOME: 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). ANALYTICAL APPROACH: 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. RESULTS: 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. LIMITATIONS: Convenience sample; small subgroups; combined exposure variable grouping Asian and African, Caribbean, and Black participants together; lack of data about mechanisms. CONCLUSIONS: 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. PLAIN-LANGUAGE SUMMARY: 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.

Challenges to Shared Decision Making About Treatment of Advanced CKD: A Qualitative Study of Patients and Clinicians.

RATIONALE & OBJECTIVE: Greater understanding of the challenges to shared decision making about treatment of advanced chronic kidney disease (CKD) is needed to support implementation of shared decision making in clinical practice. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: Patients aged≥65 years with advanced CKD and their clinicians recruited from 3 medical centers participated in semi-structured interviews. In-depth review of patients' electronic medical records was also performed. ANALYTICAL APPROACH: Interview transcripts and medical record notes were analyzed using inductive thematic analysis. RESULTS: Twenty-nine patients (age 73±6 years, 66% male, 59% White) and 10 of their clinicians (age 52±12 years, 30% male, 70% White) participated in interviews. Four themes emerged from qualitative analysis: (1) competing priorities-patients and their clinicians tended to differ on when to prioritize CKD and dialysis planning above other personal or medical problems; (2) focusing on present or future-patients were more focused on living well now while clinicians were more focused on preparing for dialysis and future adverse events; (3) standardized versus individualized approach to CKD-although clinicians tried to personalize care recommendations to their patients, the patients perceived their clinicians as taking a monolithic approach to CKD that was predicated on clinical practice guidelines and medical literature rather than the patients' lived experiences with CKD and personal values and goals; and (4) power dynamics-patients described cautiously navigating a power differential in their therapeutic relationship with their clinicians whereas clinicians seemed less attuned to these power dynamics. LIMITATIONS: Thematic saturation was based on patient interviews. Themes presented might incompletely reflect clinicians' perspectives. CONCLUSIONS: Efforts to improve shared decision making for treatment of advanced CKD will likely need to explicitly address differences between patients and their clinicians in approaches to decision making about treatment of advanced CKD and perceived power imbalances in the therapeutic relationship.

Advancing Palliative Care in Patients With CKD: From Ideas to Practice.

A palliative approach to care focuses on what matters most to patients with life-limiting illness, including chronic kidney disease (CKD). Despite recent publication of related clinical practice guidelines in nephrology, there is limited information about how to practically implement these recommendations. In this Perspective, we describe our experience integrating a palliative approach within routine care of patients with CKD glomerular filtration rate categories 4 and 5 (G4-G5) across a provincial kidney care network during the past 15 years. The effort was led by a multidisciplinary group, tasked with building capacity and developing tools and resources for practical integration within a provincial network structure. We used an evidence-based framework that includes recommendations for 4 pillars of palliative care to guide our work: (1) patient identification, (2) advance care planning, (3) symptom assessment and management, and (4) caring of the dying patient and bereavement. Activities within each pillar have been iteratively implemented across all kidney care programs using existing committees and organizational structures. Key quality indicators were used to guide strategic planning and improvement. We supported culture change through the use of multiple strategies simultaneously. Altogether, we established and integrated palliative care activities into routine CKD G4-G5 care across the continuum from nondialysis to dialysis populations.

Perspectives on Conservative Care in Advanced Kidney Disease: A Qualitative Study of US Patients and Family Members.

RATIONALE & OBJECTIVE: Little is known about perceptions of conservative care among patients with advanced kidney disease in the United States. STUDY DESIGN: Qualitative study using cognitive interviewing about attitudes regarding conservative care using decision aids on treatments for advanced kidney disease developed outside the United States. SETTING & PARTICIPANTS: 14 patients 75 years or older with advanced kidney disease, defined as estimated glomerular filtration rate≤20mL/min/1.73m2 and not receiving maintenance dialysis, and 6 of their family members. ANALYTICAL APPROACH: Thematic analysis of participants' reactions to descriptions of conservative care taken from various clinical care decision aids. RESULTS: Participants were mostly White (n=15) and had at least some college education (n=16). Four themes emerged from analysis of interviews: (1) core elements of conservative care: aspects of conservative care that were appealing to participants included a whole-person, team-based, and structured approach to care that focused on symptom management, maintaining current lifestyle, and managing health setbacks; (2) importance of how conservative care is framed: participants were more receptive to conservative care when this was framed as an active rather than passive treatment approach and were receptive to statements of uncertainty about future course of illness and prognosis; (3) an explicit approach to shared decision making: participants believed decisions about conservative care and dialysis should address considerations about risk and benefits of treatment options, family and clinician perspectives, and patients' goals, values, and preferences; and (4) relationship between conservative care and dialysis: although conservative care models outside the United States are generally intended to serve as an alternative to dialysis, participants' comments implied that they did not see conservative care and dialysis as mutually exclusive. LIMITATIONS: Themes identified may not generalize to the broader population of US patients with advanced kidney disease and their family members. CONCLUSIONS: Participants were favorably disposed to a whole-person multidisciplinary approach to conservative care, especially when framed as an active treatment approach. Models of conservative care excluding the possibility of dialysis were less embraced, suggesting that current models will require adaptation to meet the needs of US patients and their families.

Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study.

RATIONALE & OBJECTIVE: It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. STUDY DESIGN: Observational study in the Swedish Renal Registry, 2007 to 2017. SETTINGS & PARTICIPANTS: 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. EXPOSURES: RAS inhibitor versus CCB therapy initiation. OUTCOME: Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). ANALYTICAL APPROACH: HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. RESULTS: Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. LIMITATIONS: Potential confounding by indication. CONCLUSIONS: Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.

Outcomes Following Ischemic Stroke in Older Patients With CKD Stages 4 and 5: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The associations between ischemic stroke and time to dialysis initiation and/or death in adults with late-stage chronic kidney disease (CKD) have not been explored. We sought to measure the rate and factors associated with stroke in CKD stages 4 and 5 (CKD4-5) and assess the association of stroke with initiation of dialysis and death. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: Patients with CKD4-5 in Medicare 2007 to 2014. EXPOSURE OR PREDICTOR: Ischemic stroke in CKD4-5. OUTCOMES: Initiation of maintenance dialysis or death. ANALYTICAL APPROACH: Cox proportional hazard modeling assessed factors associated with ischemic stroke. A matched analysis (stroke/no stroke) estimated the cumulative incidence of incident kidney failure and death, treated as competing events. Simulations using a state transition model determined differences in expected time to kidney failure or death and death alone for patients with and without stroke with CKD5. RESULTS: 123,251 patients with CKD4 and 22,054 with CKD5 were identified. Mean ages were 81.0 and 79.2 years, respectively. Female sex (HRs of 1.21 [95% CI, 1.12-1.31] and 1.39 [95% CI, 1.04-1.86] for CKD4 and CKD5, respectively) and black race (HRs of 1.25 [95% CI, 1.12-1.39] and 1.12 [95% CI, 0.80-1.58] for CKD4 and CKD5, respectively) were factors associated with ischemic stroke. Rates for 30-day mortality were 13.3% and 18.8%, and for 1-year mortality, 40.0% and 38.2%. For patients with CKD5, kidney failure or death occurred an average of 3.6 months sooner for patients with an ischemic stroke, and death (irrespective of kidney failure), a mean of 24.3 months sooner. LIMITATIONS: Study design cannot determine causality; lack of data for stroke severity. CONCLUSIONS: Female sex and black race were associated with increased risk for stroke in CKD4 and CKD5. In CKD5, stroke was associated with a shorter time to kidney failure or death by nearly 4 months, and to death, by more than 2 years.

Experiences of US Nephrologists in the Delivery of Conservative Care to Patients With Advanced Kidney Disease: A National Qualitative Study.

RATIONALE & OBJECTIVE: It is relatively unusual for US patients with advanced chronic kidney disease (CKD) to forgo initiation of maintenance dialysis. Our objective was to describe practice approaches of US nephrologists who have provided conservative care for members of this population. STUDY DESIGN: Qualitative study using semi-structured interviews. SETTING & PARTICIPANTS: A national sample of 21 nephrologists experienced in caring for patients with advanced CKD who decided not to start dialysis. ANALYTICAL APPROACH: Grounded theory methods to identify dominant themes reflecting nephrologists' experiences with and approaches to conservative care for patients with advanced CKD. RESULTS: Nephrologists who participated in this study were primarily from academic practices (n=14) and urban areas (n=15). Two prominent themes emerged from qualitative analysis reflecting nephrologists' experiences with and approaches to conservative care: (1) person-centered practices, which described a holistic approach to care that included basing treatment decisions on what mattered most to individual patients, framing dialysis as an explicit choice, being mindful of sources of bias in medical decision making, and being flexible to the changing needs, values, and preferences of patients; and (2) improvising a care infrastructure, which described the challenges of managing patients conservatively within health systems that are not optimally configured to support their needs. Participating nephrologists described cobbling together resources, assuming a range of different health care roles, preparing patients to navigate health systems in which initiation of dialysis served as a powerful default, and championing the principles of conservative care among their colleagues. LIMITATIONS: The themes identified likely are not generalizable to most US nephrologists. CONCLUSIONS: Insights from a select group of US nephrologists who are early adopters of conservative care signal the need for a stronger cultural and health system commitment to building care models capable of supporting patients who choose to forgo dialysis.

Discussing Conservative Management With Older Patients With CKD: An Interview Study of Nephrologists.

BACKGROUND: Although dialysis may not provide a large survival benefit for older patients with kidney failure, few are informed about conservative management. Barriers and facilitators to discussions about conservative management and nephrologists' decisions to present the option of conservative management may vary within the nephrology provider community. STUDY DESIGN: Interview study of nephrologists. SETTING & PARTICIPANTS: National sample of US nephrologists sampled based on sex, years in practice, practice type, and region. METHODOLOGY: Qualitative semistructured interviews continued until thematic saturation. ANALYTICAL APPROACH: Thematic and narrative analysis of recorded and transcribed interviews. RESULTS: Among 35 semistructured interviews with nephrologists from 18 practices, 37% described routinely discussing conservative management ("early adopters"). 5 themes and related subthemes reflected issues that influence nephrologists' decisions to discuss conservative management and their approaches to these discussions: struggling to define nephrologists' roles (determining treatment, instilling hope, and improving patient symptoms), circumventing end-of-life conversations (contending with prognostic uncertainty, fearing emotional backlash, jeopardizing relationships, and tailoring information), confronting institutional barriers (time constraints, care coordination, incentives for dialysis, and discomfort with varied conservative management approaches), conservative management as "no care," and moral distress. Nephrologists' approaches to conservative management discussions were shaped by perceptions of their roles and by a common view of conservative management as no care. Their willingness to pursue conservative management was influenced by provider- and institutional-level barriers and experiences with older patients who regretted or had been harmed by dialysis (moral distress). Early adopters routinely discussed conservative management as a way of relieving moral distress, whereas others who were more selective in discussing conservative management experienced greater distress. LIMITATIONS: Participants' views are likely most transferable to large academic medical centers, due to oversampling of academic clinicians. CONCLUSIONS: Our findings clarify how moral distress serves as a catalyst for conservative management discussion and highlight points of intervention and mechanisms potentially underlying low conservative management use in the United States.

Use of Renin-Angiotensin System Blockade in Advanced CKD: An NKF-KDOQI Controversies Report.

Multiple clinical trials have demonstrated that renin-angiotensin system (RAS) blockade with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers effectively reduces chronic kidney disease (CKD) progression. However, most clinical trials excluded participants with advanced CKD (ie, estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged that initiation of RAS blockade is often associated with an acute reduction in eGFR, which is thought to be functional, but may result in long-term preservation of kidney function through the reductions in glomerular intracapillary pressure conferred by these agents. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies regarding use of RAS blockade in patients with advanced kidney disease. We review available published data on this topic and provide perspective on the impact of RAS blockade on changes in eGFRs and potassium levels. We conclude that more research is needed to evaluate the therapeutic index of RAS blockade in patients with advanced CKD.

Reliability and Utility of the Surprise Question in CKD Stages 4 to 5.

BACKGROUND: Prognostic uncertainty is one barrier to engaging in goals-of-care discussions in chronic kidney disease (CKD). The surprise question ("Would you be surprised if this patient died in the next 12 months?") is a tool to assist in prognostication. However, it has not been studied in non-dialysis-dependent CKD and its reliability is unknown. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 388 patients at least 60 years of age with non-dialysis-dependent CKD stages 4 to 5 who were seen at an outpatient nephrology clinic. PREDICTOR: Trinary (ie, Yes, Neutral, or No) and binary (Yes or No) surprise question response. OUTCOMES: Mortality, test-retest reliability, and blinded inter-rater reliability. MEASUREMENTS: Baseline comorbid conditions, Charlson Comorbidity Index, cause of CKD, and baseline laboratory values (ie, serum creatinine/estimated glomerular filtration rate, serum albumin, and hemoglobin). RESULTS: Median patient age was 71 years with median follow-up of 1.4 years, during which time 52 (13%) patients died. Using the trinary surprise question, providers responded Yes, Neutral, and No for 202 (52%), 80 (21%), and 106 (27%) patients, respectively. About 5%, 15%, and 27% of Yes, Neutral, and No patients died, respectively (P<0.001). Trinary surprise question inter-rater reliability was 0.58 (95% CI, 0.42-0.72), and test-retest reliability was 0.63 (95% CI, 0.54-0.72). The trinary surprise question No response had sensitivity and specificity of 55% and 76%, respectively (95% CIs, 38%-71% and 71%-80%, respectively). The binary surprise question had sensitivity of 66% (95% CI, 49%-80%; P=0.3 vs trinary), but lower specificity of 68% (95% CI, 63%-73%; P=0.02 vs trinary). LIMITATIONS: Single center, small number of deaths. CONCLUSIONS: The surprise question associates with mortality in CKD stages 4 to 5 and demonstrates moderate to good reliability. Future studies should examine how best to deploy the surprise question to facilitate advance care planning in advanced non-dialysis-dependent CKD.

Risks of Adverse Events in Advanced CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making. STUDY DESIGN: Prospective research cohort. SETTING & PARTICIPANTS: 1,798 participants with estimated glomerular filtration rates (eGFRs)<30mL/min/1.73m2 in the CRIC Study were followed up for a median of 5.5 years. PREDICTORS: Age, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history. OUTCOMES: ESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death. RESULTS: Baseline age of the cohort was 60 years, 46% were women, and 46% were African American. Although 52.3% of participants progressed to ESRD during follow-up, the path by which this occurred was variable. For example, predicted 1-year probabilities for a hypothetical 60-year-old white woman with eGFR of 30mL/min/1.73m2, urine protein excretion of 1.8g/d, and no diabetes or CVD (risk characteristics similar to the average participant) were 3.3%, 4.1%, and 0.3%, for first developing CVD, ESRD, and death, respectively. For a 40-year-old African American man with similar characteristics but higher systolic blood pressure, the corresponding 1-year probabilities were 2.4%, 13.2%, and 0.1%. For all participants, the development of ESRD or CVD increased the risk for subsequent mortality, with no differences by patient race or body mass index. LIMITATIONS: The CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist. CONCLUSIONS: The prognosis and timing of adverse outcomes in chronic kidney disease vary by patient characteristics. These results may help guide the development of personalized approaches for managing patients with advanced CKD.

Effect of Dapagliflozin on Serum Uric Acid Levels in Patients with Advanced Chronic Kidney Disease.

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.

The Etiology of Advanced Chronic Kidney Disease in Southeast Asia: A Meta-analysis.

INTRODUCTION: Chronic kidney disease (CKD) etiology varies greatly between developed and developing countries. In addition, differences in underlying pathogenesis and therapeutic options affect the progression towards advanced-CKD. This meta-analysis aims to identify the etiology of advanced-CKD in Southeast Asia. METHODS: A systematic search in four electronic-databases and complementary search on national kidney registries and repository libraries was conducted until July 20, 2023. The risk of bias was assessed using Newcastle-Ottawa Scale for observational studies and Version-2 of Cochrane for intervention studies. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews PROSPERO; Registration ID:CRD42022300786. RESULTS: We analyzed 81 studies involving 32,834 subjects. The pooled prevalence of advanced-CKD etiologies are diabetic kidney disease (DKD) 29.2% (95%CI 23.88-34.78), glomerulonephritis 20.0% (95%CI 16.84-23.38), hypertension 16.8% (95%CI 14.05-19.70), other 8.6% (95%CI 6.97-10.47), unknown 7.5% (95%CI 4.32-11.50), and polycystic kidney disease 0.7% (95%CI 0.40-1.16). We found a significant increase in DKD prevalence from 21% (9.2%, 95%CI 0.00-33.01) to 30% (95%CI 24.59-35.97) before and after the year 2000. Among upper-middle-income and high-income countries, DKD is the most prevalent (26.8%, 95%CI 21.42-32.60 and 38.9%, 95%CI 29.33-48.79, respectively), while glomerulonephritis is common in lower-middle-income countries (33.8%, 95%CI 15.62-54.81). CONCLUSION: The leading cause of advanced-CKD in Southeast Asia is DKD, with a substantial proportion of glomerulonephritis. An efficient screening program targeting high-risk populations (diabetes mellitus and glomerulonephritis) is needed, with the aim to delay CKD progression.

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.

"Renalism" with Renin Angiotensin Aldosterone System Inhibitor Use in Patients Enrolled in Trials for Heart Failure with Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Systematic Review.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Patient perspectives on chronic kidney disease and decision-making about treatment. Discourse of participants in the French CKD-REIN cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Four prescribed Chinese herbal medicines provide renoprotection and survival benefit without hyperkalemia risk in patients with advanced chronic kidney disease: A nationwide cohort study.

BACKGROUND: Chinese herbal medicine (CHM) has been used as adjuvant treatment of chronic kidney disease (CKD) for years. Astragalus membranaceus (A. membranaceus, Huangqi [A]), Angelica sinensis (Oliv.) Diels (Danggui [S]), Rheum palmatum L. (Dahuang [R]), and Salvia miltiorrhiza Bunge (Danshen [D]) are considered as potentially renoprotective CHMs. However, there is limited evidence on whether ASRD use affects outcomes and causes hyperkalemia in patients with stage 4 and stage 5 advanced CKD. PURPOSE: To investigate between ASRD use (vs. nonuse) and risks of end-stage renal disease (ESRD), death, and hyperkalemia in patients with advanced CKD. STUDY DESIGN: Retrospective nationwide cohort study using claims data from the Taiwan's 2005 Longitudinal Generation Tracking Database in 2000-2016. METHODS: A total of 24,572 patients with advanced CKD were identified and 15,729 eligible patients were enrolled in the propensity score matching, with 1,401 incident ASRD users (8.9%) and 14,328 nonusers (91.1%). Finally, 1,076 ASRD users and 4,304 matched nonusers were subjected to analysis. We used Cox proportional hazards regression model to estimate the hazard ratios for ESRD and death and Poisson regression to estimate incidence rate ratio of hyperkalemia. The additive effect of one to four ASRD and the pooling effect of individual ASRD on risks of ESRD and death were also addressed. RESULTS: In a total follow-up of 15,740 person-years, 2,703 patients (50.2%) developed ESRD and 499 (9.3%) died before progression to ESRD. As compared with nonusers, ASRD users were associated with adjusted hazard ratios of 0.83 (95% confidence interval, 0.76-0.91) for ESRD and 0.78 (0.30-0.93) for death, as well as adjusted incidence rate ratios of 0.54 (0.48-0.60) for inpatient hyperkalemia and 0.44 (0.42-0.46) for total hyperkalemia. The renal and survival benefits of ASRD use were consistent across almost patient subgroups on multivariate stratified analyses. Using all four ASRD provided the lowest risks of ESRD (0.30; 0.71-0.52) and death (0.32; 0.17-0.63). Individual use of ASRD also demonstrated comparable renal and survival benefits. CONCLUSION: ASRD use was associated with lower risks of ESRD and death among advanced CKD patients. This benefit did not increase hyperkalemia risk.