Long-term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study.

Background: The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk. Methods and Results: The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04-0.96; p = 0.045) and 0.16 (95%CI 0.04-0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16-0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23-1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38-0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34-0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3-3.0] vs 6.7 events per 100 person/years, p < 0.001). Conclusion: In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.

Acute kidney injury in patients with acute decompensated heart failure-cardiogenic shock: Prevalence, risk factors and outcome.

BACKGROUND: Acute Kidney Injury (AKI) represents a major complication of acute heart failure and cardiogenic shock (CS). There is a paucity of data on AKI complicating acutely decompensated heart failure patients presenting with CS (ADHF-CS). We aimed to investigate AKI prevalence, risk factors and outcomes in this subgroup of patients. METHODS: Retrospective observational study on patients admitted for ADHF-CS to our 12-bed Intensive Care Unit (ICU), between January 2010 and December 2019. Demographic, clinical, and biochemical variables were collected at baseline and during hospital stay. RESULTS: Eighty-eight patients were consecutively recruited. The predominant etiologies were idiopathic dilated cardiomyopathy (47%), followed by post-ischemic (24%). AKI was diagnosed in 70 (79.5%) of patients. Forty-three out of 70 patients met the criteria for AKI at ICU admission. On multivariate analysis, a central venous pressure (CVP) higher than 10 mmHg (OR 3.9; 95%CI 1.2-12.6; p = 0.025) and serum lactate higher than 3 mmol/L (OR 4.1; 95%CI 1.01-16.3; p = 0.048) were identified to be independently associated with AKI. Age and AKI stage were independent predictors of 90-day mortality. CONCLUSION: AKI is a common and early complication of ADHF-CS. Venous congestion and severe hypoperfusion are risk factors for AKI development. Early detection and prevention of AKI could lead to better outcome in this clinical subgroup.

Outcomes on safety and efficacy of left atrial appendage occlusion in end stage renal disease patients undergoing dialysis.

BACKGROUND: In patients with end stage renal disease and atrial fibrillation (AF), undergoing chronic dialysis, direct oral agents are contraindicated and warfarin does not fully prevent embolic events while increasing the bleeding risk. The high hemorrhagic risk represents the main problem in this population. Aim of the study was to estimate the safety and efficacy for thromboembolic prevention of left atrial appendage (LAA) occlusion in a cohort of dialysis patients with AF and high hemorrhagic risk. METHODS: Ninety-two dialysis patients with AF who underwent LAA occlusion were recruited. For comparative purposes, two cohorts of dialysis patients with AF, one taking warfarin (oral anticoagulant therapy, OAT cohort, n = 114) and the other not taking any OAT (no-therapy cohort, n = 148) were included in the study. Primary endpoints were (1) incidence of peri-procedural complications, (2) incidence of 2-year thromboembolic and hemorrhagic events, (3) mortality at 2 years. In order to evaluate the effect of the LAA occlusion on the endpoints with respect to the OAT and No-therapy cohorts, a multivariable Cox regression model was applied adjusted for possible confounding factors. RESULTS: The device was successfully implanted in 100% of cases. Two major peri-procedural complications were reported. No thromboembolic events occurred at 2-year follow-up. The adjusted multivariable Cox regression model showed no difference in bleeding risk in the OAT compared to the LAA occlusion cohort in the first 3 months of follow-up [HR 1.65 (95% CI 0.43-6.33)], when most of patients were taking two antiplatelet drugs. In the following 21 months the bleeding incidence became higher in OAT patients [HR 6.48 (95% CI 1.32-31.72)]. Overall mortality was greater in both the OAT [HR 2.76 (95% CI 1.31-5.86)] and No-Therapy [HR 3.09 (95% CI 1.59-5.98)] cohorts compared to LAA occlusion patients. CONCLUSIONS: The study could open the way to a non-pharmacological option for thromboembolic protection in dialysis patients with AF and high bleeding risk.

A simple method for the calculation of dialysis Kt factor as a quantitative measure of removal efficiency of uremic retention solutes: Applicability to high-dialysate vs low-dialysate volume technologies.

Dialysis urea removal metrics may not translate into proportional removal efficiency of non-urea solutes. We show that the Kt factor (plasma volume totally cleared of any solutes) differentiates removal efficiency of non-urea solutes in different technologies, and can easily be calculated by instant blood-dialysate collections. We performed mass balances of urea, creatinine, phosphorus and beta2-microglobulin by whole dialysate collection in 4 low-flux and 3 high-flux hemodialysis, 2 high-volume post-hemodiafiltration and 7 short-daily dialysis with the NxStage-One system. Instant dialysate/blood determinations were also performed at different times, and Kt was calculated as the product of the D/P ratio by volume of delivered dialysate plus UF. There were significant differences in single session and weekly Kt (whole dialysate and instant calculations) between methodologies, most notably for creatinine, phosphorus and beta2-microglobulin. Urea Kt messured in balance studies was almost equal to that derived from the usual plasma kinetic model-based Daugirdas' equation (eKt/V) and independent V calculation, indicating full correspondence. Non-urea solute Kt as a fraction of urea Kt (i.e. fractional removal relative to urea) showed significant differences between technologies, indicating non-proportional removal of non-urea solutes and urea. Instant Kt was higher than that in full balances, accounting for concentration disequilibrium between arterial and systemic blood, but measured and calculated quantitative solute removal were equal, as were qualitative Kt comparisons between technologies. Thus, we show that urea metrics may not reliably express removal efficiency of non-urea solutes, as indicated by Kt. Kt can easily be measured without whole dialysate collection, allowing to expand the metrics of dialytic efficiency to almost any non-urea solute removed by dialysis.

Implant success and safety of left atrial appendage occlusion in end stage renal disease patients: Peri-procedural outcomes from an Italian dialysis population.

AIMS: To estimate the safety and the efficacy of the off label left atrial appendage (LAA) occlusion in chronic dialysis patients with atrial fibrillation (AF). In this preliminary paper, we report the design of the study and the data on peri-procedural complications. METHODS: This is a prospective cohort study. Primary endpoints are i) incidence of peri-procedural complications, ii) cumulative incidence of two-year thromboembolic events iii) cumulative incidence of two-year bleedings iiii) mortality at two years. Adverse events and death within 30 days of the procedure were recorded. RESULTS: Fifty patients who underwent LAA occlusion between May 2014 and September 2017 were recruited. Both the mean age of the sample study and the dialysis duration were high [71.8 (9.6) years and 59.4 (78.2) months, respectively]. Most patients (84%) were hypertensive and 62% suffered a previous major bleeding. About half of them presented cardiovascular diseases. CHA2DS2VASCs and HASBLED scores were 4.0 (1.5) and 4.4 (0.9), respectively. Most patients (88%) showed atrial dilatation and 44% left ventricular hypertrophy; 32% had left ventricular ejection fraction <50%. Fifty five percent of patients had permanent AF and 32% paroxysmal AF. All devices were implanted successfully. No deaths or major adverse events were reported during a 30-day follow-up. Three episodes of peri-procedural access site bleeding were reported, requiring no transfusion. CONCLUSIONS: Our preliminary data suggest the feasibility and safety of LAA occlusion in patients undergoing dialysis. Only the follow-up of these patients over time can provide evidence that LAA occlusion is effective in preventing of thromboembolic events in this very high-risk population.

Phosphate and Calcium Control in Short Frequent Hemodialysis with the NxStage System One Cycler: Mass Balance Studies and Comparison with Standard Thrice-Weekly Bicarbonate Dialysis.

BACKGROUND: Short frequent dialysis with NxStage System One cycler (NSO) has become increasingly popular as home hemodialysis prescription. Short dialysis sessions with NSO might not allow adequate phosphate (P) removal. METHODS: Single-session and weekly balances of P and calcium (Ca) were compared in 14 patients treated with NSO (6 sessions/week) and in 14 patients on standard bicarbonate dialysis (BHD). RESULTS: NSO and BHD showed similar plasma P fall, with end-dialysis plasma P slightly lower in BHD (2.2 ± 0.5 vs. 2.7 ± 0.8 mg/dL, p < 0.02). Single-session P removal was lower in NSO, but weekly removal was higher (3,488 ± 1,181 mg vs. 2,634 ± 878, p < 0.003). Plasma Ca increase was lower in NSO, with similar PTH fall. Ca balance varied according to start plasma Ca, dialysate to blood Ca gradient and net ultrafiltration. CONCLUSIONS: short, frequent home hemodialysis with NSO, on a 6/week-based prescription, allows higher weekly P removal than BHD. With the dialysate Ca concentration in use (6 mg/dL), total plasma Ca and iCa concentration increase is lower in NSO.

[Dialysis and cookers: a project for the empowerment of patients in managing their own chronic renal failure].

The phosphate and potassium control is indispensable to dominate the secondary hyperparathyroidism and reduce cardiovascular mortality in dialysis patients. Most of them receive only theoretical nutritional information. We therefore organized a cooking workshop for dialysis patients, with a multidisciplinary team consisting of nurses, nephrologists, a dietitian and a professional chef, to directly teach the patients and their families how to realize a low phosphorus and potassium menu, assessing the proper use of phosphate binders, and blood tests at baseline and at three and six months. Twenty-four patients, out of 133, attended the workshop with a family member, filling out a questionnaire on eating habits, knowledge about phosphorus and potassium, and about binders. Theoretical and practical information about phosphorus and potassium metabolism, about binders, and cooking techniques were given during the evening, we then prepared a meal, eaten all together. The questionnaire was repeated at the end of the evening, and all the participants reported an improvement of the considered variables. Phosphorus and potassium plasma levels and the number of binders did not change after three and six months. Coping with the dietary changes related to the start of the dialytic therapy in an informal atmosphere, with a family member, is highly appreciated, clinically useful, logistically and economically sustainable. A customized and long-lasting counselling is probably required to modify plasma levels of phosphorus and potassium and binder's consumption. The poor dietary knowledge detected in our patients and the satisfaction about the course both confirm the training needs in this area.

Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1 beta gene: description of a new family with associated liver involvement.

BACKGROUND: Mutations in the hepatocyte nuclear factor (HNF)-1beta gene (TCF2) are responsible for a syndrome characterized by maturity-onset diabetes of the young, a nondiabetic renal disease, genital malformations, and liver dysfunction. METHODS: The HNF-1beta gene was screened for mutations in four members of an Italian family with early-onset, nonketotic diabetes or a familiar, nondiabetic renal disease and nonprogressive liver disorder. RESULTS: The genetic analysis revealed an already described nonsense mutation in codon 177 of HNF-1beta gene (R177X) in the four related subjects. Clinical features included diabetes in three of four patients, monolateral renal hypoplasia with cysts in the controlateral kidney in two patients, and bilaterally small hyperechoic kidneys without cysts in the other two patients. Renal function impairment was severe in one patient, requiring dialysis treatment, and mild in three. Three patients had nonprogressive liver dysfunction, with long-lasting enzyme alterations but no liver insufficiency or jaundice. CONCLUSION: HNF-1beta gene mutations are associated with a wide variability in severity and pattern of clinical symptoms within the same kindred regarding diabetes and renal impairment. Moderate liver dysfunction may be a so far overlooked component of the syndrome.