What Total Body Water Measurement Should Be Used for Prescribing the Dialysis Dose in Low-Flow Home Daily Dialysis?

INTRODUCTION: In low-flow home daily dialysis (HDD), the dialysis dose is evaluated from the total body water (TBW). TBW can be estimated by anthropometric methods or bioimpedance spectroscopy. METHODS: A multicentric cross-sectional study of patients in HDD for >3 months was conducted to assess the correlation and the difference between the anthropometric estimate of TBW (Watson-TBW) and the bioimpedance estimate (BIS-TBW) and to analyse the impact on the dialysate volume prescribed. RESULTS: Forty patients from 10 centres were included. The median BIS-TBW and Watson-TBW were 35.1 (29.1-41.4 L) and 36.9 (32-42.4 L), respectively. The 2 methods had a good correlation (r = 0.87, p < 0.05). However, Bland-Altman analysis showed an overestimation of TBW with Watson's formula, with a bias of 2.77 L. For 4, 5, or 6 sessions per week, the use of Watson-TBW increases the dialysate prescription per week by 100 L, 45 L, or 10 L, respectively, over our entire cohort. There is no increase in the volume of dialysate prescribed with the 7 sessions per week schedule. CONCLUSION: BIS-TBW and Watson-TBW estimation have a good correlation; however, Watson's equation overestimates TBW. This overestimation is negligible for a prescription frequency of >5 sessions per week.

Hydroxychloroquine and azithromycin tolerance in haemodialysis patients during COVID-19 infection.

BACKGROUND: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients. METHODS: We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns. RESULTS: Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days). CONCLUSIONS: HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.

Haemodialysis patients with diabetes eat less than those without: A plea for a permissive diet.

AIM: The main cause of malnutrition in haemodialysis patients is a spontaneous decline in energy and protein intakes. This study aims to report the dietary energy intake (DEI), dietary protein intake (DPI), and dietary micronutrient intake in a French HD population, to report factors associated with a low DPI and DEI, and to analyze if nutritional intake was correlated with nutritional status. METHODS: We conducted an observational cross-sectional study in a haemodialysis population of 87 adult patients in July 2014. Daily nutritional oral intake, handgrip strength, body composition measured by bioimpedancemetry, and biological and dialysis parameters were obtained from medical records. Statistical analyses of parameters associated with DEI and DPI were performed. RESULTS: The median age (interquartile range) of the population was 77.3 [71.1; 84.8] years, 57.5% were men, and 52.9% had diabetes mellitus. Median weight-adjusted DEI was 18.4 [15.7;22.3] kcal/kg per day (1308 [1078; 1569] kcal/day), and median weight-adjusted DPI was 0.80 [0.66; 0.96] g/kg per day (57.5 [47.1; 66.8] g/day). In multivariate analysis, weight-adjusted DEI was statistically lower in patients with diabetes (coefficient [95%CI] -3.81[-5.21;-2.41] kcal/kg per day; P = 0.01) but was not associated with the others parameters. When DEI was not adjusted for weight, diabetes was no longer associated with DEI, but female gender (-178[-259;-961] kcal/day; P = 0.03) and a higher Charlson comorbidity index (-30[-44;-15]; P = 0.04) were associated with a lower calorie intake. Results for DPI were similar except that the Charlson comorbidity index did not reach significance. CONCLUSIONS: Diabetes is an important factor associated with low dietary intake in haemodialysis patients. Restrictive regimens should be prescribed cautiously in haemodialysis patients, especially in those with diabetes.

The "Dose-Effect" Relationship Between 25-Hydroxyvitamin D and Muscle Strength in Hemodialysis Patients Favors a Normal Threshold of 30 ng/mL for Plasma 25-Hydroxyvitamin D.

OBJECTIVE: Muscle strength is weakened in maintenance hemodialysis patients. Strength is both a measure of a functional parameter and of frailty as it is independently associated with mortality. In the general population, observational studies show that plasma 25-hydroxyvitamin D (25[OH]D) is positively correlated with muscle strength and function. We analyzed the determinants of muscle strength measured by handgrip and 25(OH)D in a maintenance hemodialysis population. METHODS: In this observational cross-sectional study, data from all hemodialysis patients from our nephrology department were recorded in July 2014. Daily nutritional oral intake, handgrip strength, body composition measured by bioimpedancemetry analysis, as well as biological and dialysis parameters, were obtained from medical files. We used a linear regression model to assess nutritional, biological, and dialysis parameters as well as body composition associated with handgrip strength. RESULTS: The median age (interquartile range) of the 130 included patients was 77.3 (69.5-84.7) years, 57.7% were men, and 50.8% had diabetes mellitus. Median handgrip strength value (interquartile range) was 14.3 (10.6-22.2) kg. In univariate analyses, the factors associated with handgrip strength were age, gender, albumin, transthyretin, predialysis creatinine and urea, normalized protein nitrogen appearance, lean mass, and muscle mass measured by bioimpedancemetry analysis as well as phase angle, and 25(OH)D. In multivariate analyses, lower age, male gender, higher albumin, higher muscle mass, and 25(OH)D level ≥ 30 ng/mL were independently correlated with muscle strength measured by handgrip. CONCLUSIONS: This study found a positive correlation between plasma 25(OH)D and muscle strength measured by handgrip in hemodialysis patients. We report a "dose-effect" relationship between 25(OH)D and handgrip strength under 30 ng/mL, which is no more present above 30 ng/mL. Prospective randomized studies are needed to prove that supplementation with cholecalciferol, leading to 25(OH)D levels ≥ 30 ng/mL, improves muscle strength in hemodialysis patients.

Prognostic value of inducible myocardial ischemia in predicting cardiovascular events after renal transplantation.

BACKGROUND: The aims of the present study were to determine the prevalence of inducible myocardial ischemia (IMI) in renal transplant recipients (RTR) more than 50 years old, to identify predictors of IMI, and to search for its prognostic value. METHODS: Among the 377 renal transplantations performed between 1989 and 1998 in a single institution, 120 were done in patients > or =50 years old, and 97 were recruited for the study. During the last quarter of 1998, all of them underwent an exercise test (EST), an exercise-thallium 201 single photon emission computed tomography coupled with dipyridamole (SPECT), and 81% of them had a dobutamine stress echocardiography (DSE). Patients with IMI subsequently underwent coronary angiography to detect coronary stenosis. RESULTS: IMI was present in 12 of the 97 patients (10%). The diagnosis was evidenced by EST in four cases, by SPECT in 11 cases, and DSE in three cases. Five of these 12 patients (42%) had significant coronary artery stenosis (> or =50%). Multivariate analysis of several pre- and post-transplant variables evidenced acute rejection and left ventricular hypertrophy as significant correlates of IMI (both P < 0.03). Patients were prospectively followed-up for 48 months for the occurrence of major cardiovascular events. Kaplan-Meier analysis revealed a significant increase in cardiovascular events in the IMI group (P < 0.0001). In addition, the Cox proportional hazards model revealed that IMI and diabetes mellitus had an independent significant effect on the occurrence of major cardiovascular events. CONCLUSION: IMI was present in 10% of RTR aged > or =50 years, and was predicted by acute rejection and left ventricular hypertrophy. IMI had a strong effect on major cardiovascular events in this population.

Pharmacokinetics of the low molecular weight heparin enoxaparin during 48 h after bolus administration as an anticoagulant in haemodialysis.

BACKGROUND: The interest of low molecular weight heparins (LMWH) regarding bleeding risk is controversial in renal failure patients. In haemodialysis patients, there are very few data on the pharmacokinetics of LMWH after the end of the session. The aim of the study was to evaluate the duration of anticoagulation after bolus administration of the LMWH enoxaparin at the start of haemodialysis. METHODS: The pharmacokinetics of enoxaparin were studied during the 48 h following a single bolus injection at the start of the dialysis session in 30 chronic haemodialysis patients. Pharmacokinetics were determined using a population approach (Non Linear Mixed Effects Modelling). RESULTS: A single injection of enoxaparin at 60 U IU/kg (4000 +/- 455 IU) led to an anti-Xa activity higher than 1.2 IU/ml during the first 2 h of the session, and between 0.4 and 1.2 IU during the third and fourth hours. After the end of the session, anti-Xa activity remained higher than 0.4 IU/ml up to 10 h after injection, and higher than 0.1 IU/ml up to 24 h. The pharmacokinetic model showed that only weight improved the predicted vs observed anti-Xa activity plot. The model was used to simulate single and multiple dosing with decreased enoxaparin doses. Whatever the procedure, anti-Xa activity remained high (>0.22 +/- 0.99 UI/ml) up to 12 h after the start of the dialysis session. CONCLUSIONS: These results suggest that haemodialysis patients receiving the LMWH enoxaparin during dialysis are at risk of bleeding up to 10 h after the injection.

High adenosine and deoxyadenosine concentrations in mononuclear cells of hemodialyzed patients.

Infections are one of the most important complications of hemodialysis (HD). The high concentrations of adenosine (Ado) and of its metabolites during HD may contribute to the dialysis-induced immune deficiency through their known ability to alter lymphocyte function. The influence of HD on Ado metabolism was assessed in mononuclear cells through the measurement of (1) the concentrations of nucleosides in mononuclear cells and (2) the activities of mononuclear cell Ado deaminase (MCADA) and Ado kinase, two enzymes involved in Ado concentration regulation. Nine end-stage renal failure hemodialyzed patients (five men and four women; mean age, 69 +/- 10 yr) and eight healthy volunteers (four men and four women; mean age, 53 +/- 19 yr) were included in the study. Before HD, Ado, deoxyadenosine, and inosine concentrations were respectively 2.9-, 2.5-, and 2.5-fold higher in mononuclear cells of patients than in healthy volunteers. During HD, Ado concentration decreased by 34%, whereas inosine concentration increased by 27%. Before HD, MCADA activity level was 2.1-fold lower in patients than in control subjects. After HD, MCADA activity increased by nearly 50% but remained lower than in control subjects. Ado kinase activity level of patients did not differ from that of control subjects and was unchanged by HD. The influence of Ado on in vitro mononuclear cell proliferation and interferon-gamma production also was evaluated. Ado inhibited cell proliferation and interferon-gamma production in a dose-dependent manner, and these inhibitions were stronger for patients than for healthy volunteers. The high concentrations of Ado and deoxyadenosine in mononuclear cells and the low MCADA activity level likely are involved in the immune defect of patients who are undergoing HD.