Heart failure with preserved ejection fraction is the most frequent but commonly overlooked phenotype in patients on chronic hemodialysis.

Introduction: Heart failure (HF) is a serious complication of end-stage kidney disease (ESKD). However, most data come from retrospective studies that included patients on chronic hemodialysis at the time of its initiation. These patients are frequently overhydrated, which significantly influences the echocardiogram findings. The primary aim of this study was to analyze the prevalence of heart failure and its phenotypes. The secondary aims were (1) to describe the potential of N-terminal pro-brain natriuretic peptide (NTproBNP) for HF diagnosis in ESKD patients on hemodialysis, (2) to analyze the frequency of abnormal left ventricular geometry, and (3) to describe the differences between various HF phenotypes in this population. Methods: We included all patients on chronic hemodialysis for at least 3 months from five hemodialysis units who were willing to participate, had no living kidney transplant donor, and had a life expectancy longer than 6 months at the time of inclusion. Detailed echocardiography together with hemodynamic calculations, dialysis arteriovenous fistula flow volume calculation, and basic lab analysis were performed in conditions of clinical stability. Excess of severe overhydration was excluded by clinical examination and by employing bioimpedance. Results: A total of 214 patients aged 66.4 ± 14.6 years were included. HF was diagnosed in 57% of them. Among patients with HF, HF with preserved ejection fraction (HFpEF) was, by far, the most common phenotype and occurred in 35%, while HF with reduced ejection fraction (HFrEF) occurred only in 7%, HF with mildly reduced ejection fraction (HFmrEF) in 7%, and high-output HF in 9%. Patients with HFpEF differed from patients with no HF significantly in the following: they were older (62 ± 14 vs. 70 ± 14, p = 0.002) and had a higher left ventricular mass index [96(36) vs. 108(45), p = 0.015], higher left atrial index [33(12) vs. 44(16), p < 0.0001], and higher estimated central venous pressure [5(4) vs. 6(8), p = 0.004] and pulmonary artery systolic pressure [31(9) vs. 40(23), p = 0.006] but slightly lower tricuspid annular plane systolic excursion (TAPSE): 22 ± 5 vs. 24 ± 5, p = 0.04. NTproBNP had low sensitivity and specificity for diagnosing HF or HFpEF: with the use of the cutoff value of 8,296 ng/L, the sensitivity of HF diagnosis was only 52% while the specificity was 79%. However, NTproBNP levels were significantly related to echocardiographic variables, most significantly to the indexed left atrial volume (R = 0.56, p < 10-5) and to the estimated systolic pulmonary arterial pressure (R = 0.50, p < 10-5). Conclusions: HFpEF was by far the most common heart failure phenotype in patients on chronic hemodialysis and was followed by high-output HF. Patients suffering from HFpEF were older and had not only typical echocardiographic changes but also higher hydration that mirrored increased filling pressures of both ventricles than in those of patients without HF.

Significant differences between two commonly used bioimpedance methods in hemodialysis patients.

INTRODUCTION: Bioimpedance methods are currently used abundantly in patients on chronic hemodialysis. In this population, their most important role is to determine the level of fluid volume, respectively its intra- and extracellular components. There are several bioimpedance devices on the market. In this project, we compared two frequently used devices: Body Composition Monitor and InBody S10. MATERIALS AND METHODS: We invited patients on chronic hemodialysis who are being treated in our institution. Inclusion criteria were: clinically stable condition, lack of artificial joints, pacemakers, or other implanted metal objects. The examinations were performed just prior to hemodialysis by both methods 5 minutes apart. Patients were examined in the supine position after 15 minutes at rest to stabilize body fluids. Studied parameters were those that are obtainable by both methods: total body water (TBW) (L), extracellular water (ECW) (L) and intracellular water (ICW) (kg), lean tissue mass (LTM) (L), and fat tissue mass (kg). RESULTS: We included 14 participants (aged 64.4 ± 18.0 years). Statistically and clinically significant differences between data from compared devices were observed for all variables. Inbody S10 overestimated TBW by 2.58 ± 2.73 L and ICW by 4.56 ± 2.27 L in comparison to BCM. The highest difference (27%) was measured for LTM and ICW 22%. LTM, fat, and ECW were higher when measured by BCM (LTM by 8.54 ± 6.43 kg, p < 0.001; fat by 3.41 ± 4.22, p = 0.01; ECW by 2.01 ± 0.89 L, p < 0.001). CONCLUSION: The differences between tested devices were significant not only statistically, but also clinically. These two devices cannot be used interchangeably for dry weight setting of hemodialysis patients.

Population pharmacokinetics-pharmacodynamics of fondaparinux in dialysis-dependent chronic kidney disease patients undergoing chronic renal replacement therapy.

PURPOSE: Data on the anti-Xa efficacy of fondaparinux in dialysis-dependent chronic kidney disease (DD-CKD) patients are scarce. This study characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of fondaparinux in DD-CKD patients undergoing renal replacement therapy (RRT), to assess dosing strategies. METHODS: A retrospective, observational study was conducted using data on anti-Xa activity (112 samples) from 12 (3 male and 9 female) DD-CKD patients (median (IQR) age 71 years (63-88), weight 73 kg (59-98.5)). Eleven patients underwent high-flux or low-flux hemodialysis (HD) and one patient underwent peritoneal dialysis. Three patients were also treated with therapeutic plasma exchange (TPE). A non-linear mixed effects analysis was performed using NONMEM 7.3.0. RESULTS: The lab-specific slope of the relationship between fondaparinux concentration and anti-Xa levels was 1.18 IU/µg. In a one-compartment model, clearance (CL) and volume of distribution (Vd) were 0.05289 L/h and 5.55 L, respectively. High-flux HD was found to increase the CL of fondaparinux 2.26 times. TPE also considerably increased CL, but the fold-change could not be accurately estimated. Low-flux HD and peritoneal dialysis did not impact PK parameters. CONCLUSIONS: Model-based simulations showed that standard dosing (2.5 mg three times weekly before HD) results in a median anti-Xa activity of 0.55 IU/mL and 0.98 IU/mL, pre- and post-low-flux HD, respectively. In patients undergoing high-flux HD, these values are approximately 27% lower. Additional caution is warranted with TPE, as this treatment can reduce anti-Xa activity even further.

Vancomycin pharmacokinetics in patients treated with intermittent haemodialysis based on therapeutic drug monitoring.

Vancomycin is frequently used in haemodialysis (HD) patients but generally accepted target serum ranges and dosing strategy are still lacking in this group. Based on retrospective analysis of data from 118 HD patients treated with vancomycin the interdialytic elimination constant (Ke), apparent volume of distribution (Vd) and dialysis efficacy were calculated. The influence of possible clinical variables on the pharmacokinetic parameters of vancomycin have been tested. The median of Ke in interdialytic periods, corresponding half-life and Vd were 0.0073 h-1, 95.0 h and 0.87 L/kg, respectively. We found significant positive correlation between time in dialysis program and Ke. The Vd correlated best with lean body mass (LBM). For high- and low flux membrane HD of 4 hours duration the decline in vancomycin levels was 20.88% and 12.86%, respectively. Based on these data loading dose for vancomycin in HD patient should be calculated as 24.483 × LBM (kg) + 455 mg. The utility of this equation for entire HD population should be also verified prospectively.

Reduction of arteriovenous access blood flow leads to biventricular unloading in haemodialysis patients.

AIMS: Patients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes. METHODS AND RESULTS: Forty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter. CONCLUSION: The surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.

Decrease of muscle strength in vascular access hand due to silent ischaemia.

BACKGROUND:: Creation of vascular access leads to considerable local haemodynamic changes with decreased hand perfusion. Distal limb tissues then represent a model of hand ischaemia effect on muscles. The aim of our study was to investigate how the presence of vascular access influences the hand muscle strength in end-stage renal disease patients. METHODS:: We included 52 chronically haemodialysed patients with upper limb access without clinical signs of hand ischaemia. Muscle strength was evaluated by dynamometry. Finger pressure was measured on the second and fourth fingers and averaged for further analysis. Thenar tissue oxygenation (rSO2) was analysed using near-infrared spectroscopy. All examinations were performed in both the hands. Basic laboratory analysis was added. Data were processed with unpaired t-test and correlation analysis. RESULTS:: Hands with dialysis access had lower values of handgrip strength (54.2 ± 29.1 lbs vs 48.6 ± 23.4 lbs, p = 0.0006), systolic finger pressure (127.1 ± 32.0 mmHg vs 101.4 ± 31.6 mmHg, p < 10-8) and of thenar rSO2 (45.8% ± 12.9% vs 42.5% ± 13.3%, p = 0.002). Muscle strength (handgrip) was directly related to the thenar oxygenation ( r = 0.36; p = 0.014) and to the finger systolic pressure ( r = 0.38; p = 0.007) on the access extremity. On the extremity without dialysis access, handgrip strength was inversely related to patient's age ( r = -0.41, p = 0.003), dialysis vintage ( r = -0.32, p = 0.02) and red cell distribution width ( r = -0.37, p = 0.01). CONCLUSION:: The presence of dialysis access leads to the decrease of finger pressure, oxygenation, and also muscle strength even in the absence of clinically overt hand ischaemia. All these parameters are interrelated. This study underlines the consequences of inadequate muscle perfusion.

Low Cerebral Oxygenation Is Associated with Cognitive Impairment in Chronic Hemodialysis Patients.

BACKGROUND/AIMS: High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. METHODS: Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired t test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score <26). Multiple linear regression analysis was used to adjust for principal confounders. RESULTS: Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, p = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, p = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, p < 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (p = 0.007). CONCLUSION: Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.