Faculty Bibliography

Introduction/UNASSIGNED:Establishing the frequency and nature of arrhythmias in hemodialysis (HD) is an important step in improving outcomes of these patients. We undertook this systematic review and meta-analysis to characterize arrhythmia frequency in maintenance HD patients. Methods/UNASSIGNED:statistic was used to quantify heterogeneity. Results/UNASSIGNED: < 0.001) than the rate of bradycardia/asystole reported in the same patients. Incidence of atrial fibrillation (AF) varied significantly across the studies (from 0.07 to 0.83 patients per year) reflecting variable definitions (new-onset vs. total number of episodes). Conclusion/UNASSIGNED:The incidence of arrhythmias among chronic HD patients is high, with bradycardia/asystole occurring more frequently than ventricular arrhythmias. Additional studies to refine estimates particularly of AF are needed.

Background: Heart failure (HF) is an important contributor to the increased cardiovascular (CV) mortality incidence in ESKD. Therapies targeting HF's unique pathophysiology in ESKD are lacking. Hydralazine-isosorbide dinitrate (H-ISDN) targets reduced nitric oxide bioavailability and could improve CV mortality in ESKD Methods: Adult patients with HF on maintenance dialysis between January 2011 and December 31, 2016 were identified using the United States Renal Data System. There were 6306 patients with at least one prescription for H-ISDN and 75,851 non-users. The primary outcome was death from any cause. Secondary outcomes included cardiovascular death and sudden death. Treatment effects were estimated using stabilized inverse probability weights in Cox proportional hazards regression. Because H-ISDN has been shown to improve outcomes in Black HF patients, we investigated effect modification by race Results: Age was similar in H-ISDN users (66 +/- 13 years) and non-users (69 +/- 13 years) with 50% and 51% men, respectively. H-ISDN (51%) users were more likely to be of Black race than non-users (27%). Dialysis vintage was longer in H-ISDN (25 months) users compared with non-users (15 months). All characteristics were well balanced in weighted models. Risks of all-cause mortality, cardiovascular death, and sudden death were significantly reduced in H-ISDN users compared to non-users (Table). We did not identify significant effect modification by race (Figure)
Conclusion(s): To our knowledge, this is the first analysis of the impact of H-ISDN on mortality in ESKD. Our results suggest that combination H-ISDN improves survival in dialysis patients with HF

BACKGROUND & AIMS/OBJECTIVE:Hyponatremia is an important predictor of early death among cirrhotic patients in the orthotopic liver transplantation (OLT) waiting list. Evidence exists that prioritizing OLT waiting list according to the MELD score combined with plasma sodium concentration might prevent pre transplantation death. However, the evolution of plasma sodium concentrations during the perioperative period of OLT is not well known. We aimed to describe the evolution of perioperative sodium concentration during OLT and its relation to perioperative neurohormonal responses. METHODS:Twenty-seven consecutive cirrhotic patients who underwent OLT were prospectively included in the study over a period of 27 months. We studied the evolution of plasma sodium levels, the hemodynamics, the neurohormonal response and other biological markers during the perioperative period of OLT. RESULTS:Among study's population, four patients had hyponatremia before OLT, all with Child cirrhosis. In patients with hyponatremia, plasmatic sodium reached normal levels during surgery, and sodium levels remained within normal ranges 1 day, 7 days, as well as 6 months after surgery for all patients. Creatinine clearance was decreased significantly during the perioperative period, while creatinine and cystatin C levels increased significantly. Neutrophil gelatinase-associated lipocalin (NGAL) and vasopressin levels did not change significantly in this period. Plasma renin activity, concentrations of norepinephrine and brain natriuretic peptide varied significantly during the perioperative period. CONCLUSION/CONCLUSIONS:In our study, plasmatic sodium concentrations among hyponatremic cirrhotic patients undergoing OLT seem to reach normal levels after OLT and remain stable six months after surgery providing more evidence for the importance of sodium levels in prioritization of liver transplant candidates. Further investigation of rapid correction and stabilization of sodium levels after OLT, as observed in our study, would be of interest in order to fully understand the mechanisms involved in cirrhosis-related hyponatremia, its prognostic value and clinical implications.

PURPOSE OF REVIEW/OBJECTIVE:Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment. RECENT FINDINGS/RESULTS:Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily). SUMMARY/CONCLUSIONS:DOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.

RATIONALE & OBJECTIVE:Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). STUDY DESIGN:Population-based retrospective cohort study. SETTINGS & PARTICIPANTS:All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. EXPOSURE:). OUTCOMES:The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. ANALYTICAL APPROACH:High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. RESULTS:. No interaction was detected for the outcome of hemorrhage. LIMITATIONS:Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. CONCLUSIONS:DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The relative efficacy and safety of apixaban compared with no anticoagulation have not been studied in patients on maintenance dialysis with atrial fibrillation. We aimed to determine whether apixaban is associated with better clinical outcomes compared with no anticoagulation in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:This retrospective cohort study used 2012-2015 US Renal Data System data. Patients on maintenance dialysis with incident, nonvalvular atrial fibrillation treated with apixaban (521 patients) were matched for relevant baseline characteristics with patients not treated with any anticoagulant agent (1561 patients) using a propensity score. The primary outcome was hospital admission for a new stroke (ischemic or hemorrhagic), transient ischemic attack, or systemic thromboembolism. The secondary outcome was fatal or intracranial bleeding. Competing risk survival models were used. RESULTS:=0.004. A trend toward fewer ischemic but more hemorrhagic strokes was seen with apixaban compared with no treatment. No significant difference in the composite outcome of myocardial infarction or ischemic stroke was seen with apixaban compared with no treatment. Compared with no anticoagulation, a significantly higher rate of the primary outcome and a significantly higher incidence of fatal or intracranial bleeding and of hemorrhagic stroke were seen in the subgroup of patients treated with the standard apixaban dose (5 mg twice daily) but not in patients who received the reduced apixaban dose (2.5 mg twice daily). CONCLUSIONS:In patients with kidney failure and nonvalvular atrial fibrillation, treatment with apixaban was not associated with a lower incidence of new stroke, transient ischemic attack, or systemic thromboembolism but was associated with a higher incidence of fatal or intracranial bleeding.

INTRODUCTION:The effect of mineralocorticoid receptor antagonists (MRAs) on chronic kidney disease (CKD) progression in patients with heart failure (HF) and with or without preexisting CKD has not been adequately studied. METHODS:We conducted a retrospective cohort study including consecutive adult patients followed at the HF clinic of a tertiary care center who had already been on an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). Exposure to MRAs was assessed at 6 months from registration. Patients who were never exposed to an MRA were the control group. RESULTS:A total of 314 patients who were prescribed an MRA were compared to 1,116 patients who never received an MRA. Among them, 121 and 408 patients, respectively, had CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). MRAs had to be discontinued in 36/121 patients with CKD (29.8%) and 57/165 patients without CKD (34.5%) (p = 0.39). MRA treatment was associated with a higher risk for persistent creatinine doubling among patients without CKD (hazard ratio 4.07, 95% confidence interval 1.41-11.73). A numerically lower risk was identified among CKD patients (hazard ratio 0.33, 95% confidence interval 0.04-2.78) (p for interaction = 0.009). The primary safety outcome, a composite of any doubling of serum creatinine or any episode of serious hyperkalemia (K+ >6 mmol/L), occurred more commonly in MRA users compared with nonusers in the subgroup of patients without CKD, but not in CKD patients (p for interaction = 0.02). CONCLUSION:MRA treatment in addition to an ACEI or an ARB could be safely prescribed in HF patients with CKD as it is not associated with persistent renal function decline, acute kidney injury, or serious hyperkalemia, compared with ACEI/ARB monotherapy.