VITADIAL "Does correction of 25 OH-VITAmin D with cholecalciferol supplementation increase muscle strength in hemoDIALysis patients?": study protocol for a randomized controlled trial.

BACKGROUND: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength. METHODS/DESIGN: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective. DISCUSSION: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength. TRIAL REGISTRATION: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.

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.

Plasma Retinol Concentration Is Mainly Driven by Transthyretin in Hemodialysis Patients.

OBJECTIVE: Micronutrients deficiencies in hemodialysis patients are due to low dietary intakes and intradialytic losses for hydrophilic micronutrients. Conversely, lipophilic nondialyzable compounds might accumulate because of a lack of elimination through renal metabolism or dialysis. Other compounds have complex metabolism: their concentration is not explained by these phenomenons. The aim of this study was to report plasma concentrations of lipophilic micronutrients in hemodialysis patients and to analyze if these concentrations were predictive of mortality. DESIGN: The design was monocentric observational longitudinal study. SUBJECTS: A total of 123 hemodialysis patients included in this observational study. MAIN OUTCOME MEASURE: Plasma concentration of lipophilic micronutrients retinol and its two co-transporters transthyretin and retinol-binding protein 4, tocopherol, and carotenoids (α-carotene and ß-carotene, ß-cryptoxanthin, lycopene, lutein, and zeaxanthin), and all factors associated with 1-year mortality. RESULTS: Within the 123 patients of the study, median age (interquartile range) was 77.5 (69.5-84.5) years and 58.5% were male. Median retinol plasma concentration was 4.07 (2.65-5.51) µmol/L, and 91.9% of patient had high plasma retinol concentrations. In monovariate analysis, retinol levels were inversely correlated with mortality (hazard ratio = 0.57 [0.45-0.72]; P < .001). This effect remained significant after adjustment with several parameters. Nevertheless, the correlation between retinol and mortality disappeared as soon as transthyretin was added in the statistical model, suggesting an effect of transthyretin as confusing bias. Median tocopherol plasma concentration was 34.8 (28.3-42.9) µmol/L and 72.4% of patients had high plasma tocopherol concentration. Neither tocopherol plasma levels nor carotenoids concentrations were correlated with death in multivariate analysis. CONCLUSIONS: In hemodialysis patients, the correlation between retinol plasma concentration and mortality represents the nutritional status but not a direct biological effect of retinol. Retinol is only a surrogate predictor of mortality. It might not represent vitamin A levels, but likely the transthyretin level. Plasma retinol levels should be interpreted cautiously in hemodialysis patients.

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 diagnosis of sarcopenia is mainly driven by muscle mass in hemodialysis patients.

BACKGROUND & AIMS: Sarcopenia is a well-known complication of protein energy wasting in hemodialysis patients. Its diagnosis requires measurements of muscle mass and muscle function. Few studies have reported its prevalence in hemodialysis patients. In this study, we report the prevalence of sarcopenia in this population and evaluate the performance of other parameters for its diagnosis. METHODS: In this observational cross-sectional study, data from hemodialysis patients from our nephrology department were recorded. Body composition measured by bioimpedancemetry analysis and muscle strength measured by handgrip were recorded. Normal values for sarcopenia were those recommended by the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: The median age (interquartile range) of the 111 patients was 77.5 (70.8-84.8) years. A large majority of 88.3% (n = 98) of patients had a low muscle strength; a low muscle mass index was present in 33.3% (n = 37) of the population. Finally, 31.5% (n = 35) of patients had sarcopenia. These latter were older, had longer dialysis vintage, lower BMI, mid-arm circumference and mid-leg circumference, and a lower prealbumin. The best parameter predicting sarcopenia was BMI (ROC curve AUC of 0.79 [0.68-0.91] (p < 0.001) in men and 0.81 [0.68-0.93] (p = 0.003) in women). Mid-arm circumference predicted sarcopenia, but was less accurate than BMI. Mid-leg circumference predicted sarcopenia only in men. Predialysis creatinine or creatinine index could not predict sarcopenia. CONCLUSIONS: We report a 31.5% prevalence of sarcopenia in hemodialysis patients. The diagnosis of sarcopenia was mainly driven by muscle mass measurement because muscle strength is low in the large majority of hemodialysis patients.

Electrolytes-Enriched Hemodiafiltration Solutions for Continuous Renal Replacement Therapy in Acute Kidney Injury: A Crossover Study.

AIMS: To evaluate the capability of an electrolytes-enriched solution to prevent metabolic disorders during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: Serum biochemistry and clinical tolerance were compared during CVVHDF treatments with an electrolyte-enriched (Phoxilium) or standard solutions in 10 acute renal failure patients. RESULTS: As compared to standard fluids, serum potassium and phosphate levels were maintained in the normal range with Phoxilium without any supplementation but total serum calcium levels were significantly lower. Bicarbonatemia was slightly higher (24-26 vs. 21.5-24.5 mmol/l, p < 0.05) with conventional solutions and was associated with a significant increased level of pH (>7.44). Despite the absence of glucose in the Phoxilium solution, blood glucose levels and glucose supplementation were similar between treatments. Clinical tolerance and efficiency of CVVHDF sessions were comparable. CONCLUSION: Phoxilium effectively prevented hypophosphatemia and hypokalemia during CVVHDF. It was, however, associated with a slight metabolic acidosis and hypocalcemia compared with conventional solutions.

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.

[Drugs: an underestimated cause of arterial hypertension]. / Meédicaments: une cause sous-estimée d'hypertension artérielle.

In Switzerland, as in other Occidental countries, the prevalence of arterial hypertension (AHT) in the adult population is around 30-40%. Among the causes of secondary AHT, drug induced hypertension is sometimes omitted. Many molecules can induce AHT or worsen it due to an interaction with anti hypertensive drugs. Among these, NSAIDs and anti depressants, widely prescribed, should be used with caution, particularly in patients at risk, namely: those with preexisting AHT, the elderly, or patients suffering from kidney disease, diabetes, and/or heart failure. Increases in blood pressure have also been described with anti-vascular endothelial growth factor (VEGF) drugs, used in the treatment of (metastatic) cancer. A thorough anamnesis of drugs, including over the counter ones, should be performed in every hypertensive patient, and can avoid cumbersome and unnecessary investigations and therapy.

[Interpretation of volemia in acute kidney injury]. / Interprétation de la volémie dans l'insuffisance rénale aiguë.

Assessment of volume status is often challenging in daily clinical practice. One of the clinician's tasks is to prevent or to treat organ systems failures that arise from a mismatch between the transport of oxygen and metabolic needs. Renal failure is a frequently encountered in-hospital diagnosis that is known to alter significantly the prognosis. In patients with acute renal failure in particular, the consequences of an inadequate volume management further increase morbidity and mortality.