Wolfgang C. Winkelmayer

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are first-line treatment for hypertension in chronic kidney disease (CKD). However, guidelines do not recommend subsequent medication classes if additional blood pressure-lowering effect is desired. Methods: This target trial emulation using national outpatient data from the Veterans Health Administration from January 1, 2010, to December 31, 2016, included adults with non-dialysis CKD stages G1-G5 on an ACEi/ARB who initiated treatment with a second antihypertensive medication, classified as a thiazide diuretic, loop diuretic, calcium channel blocker, or β-blocker. Outcomes included composite cardiovascular events (fatal or nonfatal myocardial infarction or stroke, hospitalization for heart failure, coronary revascularization), all-cause death, and composite kidney outcomes (dialysis initiation, kidney transplantation, sustained creatinine doubling). Clinically important characteristics were included as covariates in the analysis. Results: Of 150,369 individuals already on ACEi/ARB treatment, 45,836 (30%) were prescribed a thiazide diuretic, 17,589 (12%) a loop diuretic, 33,172 (22%) a calcium channel blocker, and 53,772 (36%) a β-blocker. Those receiving thiazide diuretics and calcium channel blockers had the highest baseline blood pressure. Those receiving loop diuretics were more likely to have more advanced CKD or heart failure. Over a median (IQR) follow-up of 1282 (621, 1979) days, compared to thiazide diuretics, cardiovascular event risk was higher for calcium channel blockers, aHR 1.18 (95% CI 1.15-1.22), β-blockers, aHR 1.63 (95% CI 1.58-1.67), and loop diuretics, aHR 1.97 (95% CI 1.90-2.04). Composite kidney outcomes were also higher with calcium channel blockers, aHR 1.42 (95% CI 1.33-1.52), β-blockers, aHR 1.13 (95% CI 1.06-1.21), and loop diuretics, aHR 1.98 (95% CI 1.83-2.15). Conclusions: Adding a thiazide diuretic rather than a calcium channel blocker, β-blocker, or loop diuretic on top of ACEi/ARB treatment was associated with favorable clinical outcomes among people with CKD.

The prevalence of atrial fibrillation (AF) is high among patients with chronic kidney disease (CKD). While patients with CKD Stages G1 – G3b may be treated similarly to patients without CKD, little evidence guides therapeutic strategies for CKD G4 - G5 patients. Dosing of most drugs used for rate and rhythm control requires adjustment to kidney function. Recurrence rates after cardioversion and ablation for rhythm control are higher in patients with advanced CKD than those without it. Regarding the prevention of stroke and systemic embolism, the benefit-to-risk ratio of oral anticoagulation (OAC) is disputed among patients with CKD stages G4 - G5 with AF, in particular among those receiving hemodialysis given their high risk for severe bleeding events. Novel strategies for stroke and systemic embolism prevention, particularly factor XI inhibitors and left atrial appendage occlusion (LAAO), have not yet fulfilled their initial promise as safe and effective alternatives.

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Background: In March 2020, responding to the COVID-19 pandemic, US public health emergency waivers enabled kidney care providers (nephrologists and advanced practice providers) to substitute face-to-face in-center hemodialysis visits with telemedicine encounters. Methods: We merged an electronic health records database from dialysis patients at clinics owned by DaVita Inc. with Medicare claims-based records. We identified dialysis patients in the first six months of the pandemic. Kidney care providers were divided into those who used telemedicine frequently (above median) versus less frequently (below median) during the first three months of the pandemic. In multivariable regression models controlling for patient, kidney care provider, dialysis facility, and geographic characteristics, and the value of each outcome prior to the pandemic, we examined associations among telemedicine use by kidney care providers and hemodialysis-related surrogate health outcomes. Results: We identified 782 kidney care providers who saw patients at DaVita facilities from 4/2020-9/2020. Higher intensity (vis-à-vis telemedicine) kidney care providers documented the use of telemedicine in 86% (Standard Deviation (SD) 16%) of patients in the first three months of the pandemic, while lower intensity providers documented its use in 15% (SD 13%) of patients. Higher telemedicine use was associated with a 0.7% (95% confidence interval (CI), 0.1%-1%) reduction in the absolute probability of having a serum albumin 5.5 mg/dl. Telemedicine use was not significantly associated with outcomes related to anemia management targets, blood pressure, dialysis efficiency, interdialytic weight gain, and dialysis prescription changes. Conclusions: Patients of providers who used telemedicine more frequently had slightly better surrogate outcomes in nutritional parameters, but not in other dialysis-related health outcomes. These findings suggest that telemedicine can be employed for in-center hemodialysis visits without compromising conventional metrics of the quality of hemodialysis care.

Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently coexist, share risk factors and pathophysiology, and confer a high burden of stroke, bleeding, heart failure, and premature death. Risk scores such as CHA₂DS₂-VASc, which estimates thromboembolic risk, and HAS-BLED, which estimates bleeding risk, were derived in populations including relatively few patients with advanced CKD. Consequently, they may not adequately account for CKD-specific modifiers of thromboembolic and hemorrhagic risk. Although these scores do not formally incorporate competing non-stroke mortality, higher CHA₂DS₂-VASc scores may indirectly identify patients with a greater competing risk of death. Meanwhile, widespread use of renin–angiotensin–aldosterone system blockade, mineralocorticoid receptor antagonists, sodium–glucose cotransporter 2 inhibitors, and glucagon-like peptide–1 receptor agonists has reshaped cardiorenal prognosis, further challenging historical calibrations of stroke and bleeding scores. In this perspective, we critically appraise conventional risk scores in AF with CKD, highlight their limitations in the context of modern preventive therapies and competing mortality, and outline priorities for more dynamic, kidney–focused risk stratification.

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Introduction Apixaban reduces thromboembolic events, bleeding, and mortality compared with warfarin in patients with nonvalvular atrial fibrillation (NVAF). However, evidence in patients with kidney failure (KF) receiving peritoneal dialysis (PD) is limited. We evaluated the safety and effectiveness of apixaban versus warfarin in this population. Methods Using the US Renal Data System, we identified Medicare beneficiaries on PD with newly diagnosed NVAF (2014–2019) who had no prior oral anticoagulation (OAC) use. We included patients initiating apixaban or warfarin within 30 days after NVAF diagnosis. After propensity matching we estimated the hazard ratios for thromboembolic events, bleeding events, and mortality using Cox models accounting for competing risks, where applicable, and using both intent-to-treat and as-treated approaches. Results Among 6,571 OAC-naive PD patients with newly-diagnosed NVAF, 334 initiated apixaban and 717 initiated warfarin within 30 days. After 1:1 propensity matching, all observed characteristics of 330 apixaban and 330 warfarin users were balanced. The median CHA₂DS₂-VASc score was 4 (IQR 3-5). In intent-to-treat analyses, hazards of ischemic stroke (HR=0.92; 95%CI, 0.42-2.01) and the composite of other thromboembolic outcomes with cardiovascular death (HR=0.90; 95%CI, 0.66-1.22) did not differ between groups. The hazards of clinically important bleeding (HR=0.81; 95%CI, 0.62-1.07), major bleeding, intracranial hemorrhage, and all-cause mortality also did not differ between groups. Findings were consistent in as-treated analyses. Discussion Among PD patients with newly-diagnosed NVAF, we observed no statistically significant differences between apixaban and warfarin for effectiveness or bleeding outcomes. Given the challenges of warfarin management in KF, apixaban may represent a more practical option when anticoagulation is pursued.

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a prevalence and incidence significantly higher in adults with CKD compared with the general population. This risk increases with reduced kidney function, affecting up to 25% of all patients with CKD and 30% of those on receiving chronic dialysis. AF is associated with increased morbidity and mortality, including higher risks of stroke, heart failure, myocardial dysfunction, and progression to kidney failure. The bidirectional relationship between AF and CKD is driven by a convergence of traditional risk factors—such as hypertension and diabetes—and CKD-specific abnormalities. Key pathophysiologic mechanisms include systemic inflammation, oxidative stress, autonomic dysfunction, and disordered mineral metabolism. These factors promote structural remodeling, atrial fibrosis, and electrical instability, creating a highly arrhythmogenic substrate. Treatment options for AF include anticoagulation, rate and rhythm control medications, other cardiovascular therapies ( e.g ., sodium glucose cotransporter 2 inhibitors), and procedures aimed at normalizing rhythm and reducing stroke risk. Patients with CKD are often undertreated with AF medications and procedures, in part because of lack of robust randomized clinical trial data on efficacy and safety, particularly with advanced CKD. This narrative review summarizes key literature on the epidemiology, risk factors, mechanisms and treatment of AF in adults with CKD, and highlights critical areas for future research.

Key Points: Many major adverse cardiovascular events happen within the first 6 months after hemodialysis initiation. Using nondialyzable β -blockers at hemodialysis initiation was associated with fewer cardiovascular events than dialyzable β -blockers. Background: How β -blocker dialyzability affects cardiovascular outcomes in patients receiving hemodialysis remains unclear. Previous observational studies show conflicting results, and conducting clinical trials in this population has proven challenging. This uncertainty has contributed to substantial variation in β -blocker prescribing patterns across regions and clinicians. Methods: Using data from the United States Renal Data System, we identified patients receiving β -blockers on the day of starting hemodialysis and classified them into nondialyzable and dialyzable exposure groups. Geographical variations in nondialyzable and dialyzable β -blocker prescription rates across neighboring regions in each state were leveraged as an instrumental variable. The treatment effect of nondialyzable versus dialyzable β -blockers on major adverse cardiovascular events (MACE) at 6 months, 1 year, and 3 years was evaluated using instrumental variable g -estimation methods for survival outcomes. MACE comprised myocardial infarction, stroke, and all-cause mortality. Results: The cohort of 40,313 participants from 41 US states experienced 25,720 MACE over the 3-year follow-up period (median years [interquartile range], 1.4 [0.4–3.0]), with more than 42% occurring during the first 6 months after hemodialysis initiation. The instrumental variable met all statistical assumptions. Nondialyzable β -blockers were associated with significantly lower risk of MACE at all three follow-up time points compared with dialyzable β -blockers (hazard ratios [95% confidence intervals], 0.82 [0.74 to 0.90], 0.85 [0.79 to 0.92], and 0.90 [0.85 to 0.96], respectively). Similar patterns were observed for each separate component of MACE. Conclusions: The use of nondialyzable β -blockers compared with dialyzable β -blockers was associated with a lower risk of MACE during all time points, including the early, high-risk period in the 6 months following hemodialysis initiation.