Estimating Extracellular Fluid Volume in Healthy Individuals: Evaluation of Existing Formulae and Development of a New Equation

peer reviewedIntroduction: Several clinical settings require an accurate estimation of the physiologically expected extracellular fluid volume (ECFV). We aimed to analyze the performances of existing ECFV-estimating equations and to develop a new equation. Methods: The performances of 11 ECFV-estimating equations were analyzed in 228 healthy kidney donor candidates (Bichat Hospital, Paris, France) who underwent ECFV measurement using the distribution volume of 51Cr-labeled EDTA (51Cr-EDTA). An equation was developed using a penalized linear modeling approach (elastic net regression) and externally (Tenon Hospital, Paris, France, N = 142) validated. Results: Participants from Bichat (mean age 45.2 ± 12.0 years, 43.0% men) and Tenon (47.8 ± 10.3 years, 29.6% men) hospitals had a mean measured ECFV of 15.4 ± 2.8 l and 15.1 ± 2.1 l, respectively. Available ECFV-estimating formulae have highly variable precision and accuracy. The new equation incorporating body weight, height, sex, and age had better precision and accuracy than all other equations in the external validation cohort, with a median bias of −0.20 (95% CI: −0.35 to −0.05) l versus −2.63 (−2.87 to −2.42) l to −0.57 (− 0.83 to −0.40) l and 0.21 (0.12 to 0.43) l to 2.89 (2.65 to 3.11) l, for underestimating and overestimating equations, respectively, an interquartile range for the bias of 0.88 (0.70 to 1.08) l versus 0.91 (0.71 to 1.20) l to 1.93 (1.67 to 2.25) l, and an accuracy within 10% of 90.9% (83.8 to 94.4) versus 88.0% (81.0 to 92.3) to 8.5% (4.2 to 13.4). These results were consistent across subgroups defined by sex, body mass index (BMI), body surface area (BSA), age, and ethnicity. Conclusion: We developed and validated a new equation to estimate the individual reference value of ECFV, which is easily usable in clinical practice. Further validation in cohorts including individuals of extreme age and corpulence remains needed

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry

International audienceBackground: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival.Methods: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data.Results: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose.Conclusion: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used

Association Between Serum Kynurenine Levels and Cardiovascular Outcomes and Overall Mortality in CKD

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Association between Urate-Lowering Therapy and Kidney Failure in Patients with CKD

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Risk of acute kidney injury, end-stage kidney disease and mortality associated with proton pump inhbitor use in patients with chronic kidney disease

56th Congress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA) - Burden, Access and Disparities in Kidney Disease, Budapest, HUNGARY, JUN 13-16, 2019International audienc

One-Year Frailty Transitions Among Persons With HIV Aged 70 Years or Older on Antiretroviral Treatment

International audienceBackground. People with HIV (PWH) are aging. Frailty is an age-related condition predictive of hospitalization and mortality. Here, we assessed the frequency and factors associated with frailty transitions at 1-year follow-up in elderly PWH. Methods. Five hundred eight PWH aged 70 years or older who were on antiretroviral treatment were included in the French multicenter SEPTAVIH study in 2019-2020. Participants were classified as robust, prefrail, or frail according to Fried frailty phenotype at baseline and at 1 year. Logistic regression models were used to evaluate socioeconomic and medical factors associated with transition between frailty states. Models were adjusted for gender, age at baseline, education, and period of HIV diagnosis (before vs after 1996). Results Seventeen PWH died during the 1-year follow-up. Of the remaining 491 PWH (median age, 73 years), frailty status worsened for 18% of participants and improved for 14% at 1 year. Advanced age, baseline CD4+ T-cell count <350 cells/mm(3), and type 2 diabetes were associated with transition from prefrailty to frailty (adjusted odds ratio [aOR], 1.10 per 1-year positive difference; 95% CI, 1.01-1.20; aOR, 3.05; 95% CI, 1.14-8.18; and aOR, 2.63; 95% CI, 1.05-6.57; respectively). Being female was associated with more frequent improvement from prefrailty to robustness (aOR, 2.50; 95% CI, 1.09-5.55). Conclusions. Preventing frailty in elderly PWH is a long-term problem, beginning with the early diagnosis of HIV infection and the management of comorbidities

#1135 Evaluation of the adequacy of urate lowering therapy prescriptions in patients with chronic kidney disease: results from the CKD-REIN cohort

International audienceBackground and Aims Urate Lowering Therapy (ULT) is frequently prescribed to patients with chronic kidney disease (CKD). However, these prescriptions are often inadequate when considering kidney function. Studies evaluating the appropriateness of ULT in the CKD population are predominantly cross-sectional. Yet, the evolution and reassessment of prescriptions remain unexplored in this context. This study aims to assess the prevalence of inappropriate ULT prescriptions (whether contraindications or inappropriately high doses) with regard to kidney function in patients with CKD. Method We used 5-year longitudinal data from the CKD-REIN cohort, a nationwide sample of 3033 nephrology outpatients with moderate-to-advanced CKD. Prescriptions for colchicine, used in the treatment of acute gout attacks, and ULT, such as allopurinol and febuxostat, were prospectively recorded. An inappropriate prescription was defined as the reported prescription of either a contraindicated drug, an indicated drug at an inappropriately high dose level, or a non-recommended prescription relative to the patient's eGFR, as estimated with de-indexed CKD-EPI equation and according to the European (or French if not available) summary of product characteristics. For patients initiating ULT during follow-up, uric acid levels were compared six months before and after the initiation of ULT. Results At baseline, 987 (33%) out of the 3033 included patients (mean ± standard deviation age 67 ± 13 years, 65% men) were prescribed ULT, with 781 (26%) receiving allopurinol and 206 (7%) receiving febuxostat. Compared to patients without a prescription for ULT, those with a ULT prescription were more frequently male, older, had lower kidney function, higher cardiovascular comorbidities, and were more commonly prescribed diuretics and inhibitors of the renin-angiotensin system. Moreover, their uric acid levels were lower (patients with ULT prescription 377.0 ± 110.4 µmol/L versus without ULT prescription 456.5 ± 116.4 µmol/L, p &lt; 0.001). Notably, 316 (40%) allopurinol prescriptions were prescribed at inappropriately high dosages, while 77 (37%) febuxostat prescriptions were not recommended (resulting in a total of 393 (40%) inappropriate ULT prescriptions at baseline). Of the 54 colchicine prescriptions, one-third (n = 18) were contraindicated according to kidney function and nine were prescribed “on-demand” for crisis anticipation. During a median follow-up of 5.0 [1st-3rd quartile, 4.0–5.1] years, 253 patients were newly prescribed allopurinol and 176 were newly prescribed febuxostat, 54 (21%) out of 253 new allopurinol prescriptions were at inappropriately high dosages, and 68 (39%) out of the 176 new febuxostat prescriptions were not recommended based on the patient's kidney function (Figure). The majority of initially inappropriate ULT prescriptions (n = 393) remained so during follow-up (274 (70%)). Among the 179 patients initiating ULT during follow-up and with available data on uric acid levels, there was a significant decrease in uric acid levels after ULT initiation compared to before initiation (before: 494.5 ± 146.2 µmol/L versus after 408.5 ± 130.9 µmol/L, p &lt; 0.001). A total of 197 patients had initiated colchicine during follow-up, with 61 (31%) receiving contraindicated prescriptions, and 18 (9%) having “on-demand” prescriptions. Conclusion Our findings emphasize the lack of reassessment of ULT prescriptions during the follow-up of patients with CKD. Colchicine prescriptions in case of severe kidney impairment persist despite contraindications. Further evaluation is required to understand the association between ULT prescriptions and the progression of kidney disease

Antihypertensive Treatment Patterns in CKD Stage 3 and 4: The CKD-REIN Cohort Study

International audienceRationale &amp; ObjectiveBlood pressure (BP) control is essential for preventing cardiorenal complications in chronic kidney disease (CKD), but most patients fail to reach BP target. We assessed longitudinal patterns of antihypertensive drug prescription and systolic BP (SBP).Study DesignProspective observational cohort studySetting &amp; Population2755 hypertensive patients with CKD stages 3–4, receiving care from a nephrologist, from the French CKD-REIN cohort studyExposurePatient factors, including sociodemographic characteristics, medical history, and laboratory data, and provider factors, including number of primary-care physician and specialist encounters.OutcomesChanges in antihypertensive drug class prescription during follow-up: add-on, or withdrawal.Analytical ApproachHierarchical shared-frailty models to estimate hazard ratios (HR) to deal with clustering at the nephrologist level, and linear mixed models to describe Systolic BP trajectory.ResultsAt baseline, median age was 69, mean eGFR, 33 ml/min/1.73m2; 66% of patients were men, 81% had BP ≥130/80 mmHg and 75% were prescribed ≥2 antihypertensive drugs. During a median 5-year follow-up, the rate of changes of antihypertensive prescription was 50 per 100 person-years, 23 per 100 for add-ons and 25 per 100 for withdrawals. After adjusting for risk factors, Systolic BP, and the number of antihypertensive drugs, poor medication adherence was associated with increased HR for add-on, 1.35 (95% confidence interval, 1.01-1.80), while a shorter education level was associated with increased HR for withdrawal, 1.23 (1.02-1.49) for 9-11 years versus ≥12 years. More frequent nephrologist visits (≥4 versus none) were associated with higher HRs of add-on and withdrawal (1.52; 95% CI 1.06-2.18 and 1.57; 1.12-2.19, respectively), while associations with visit frequency to other physicians varied with their specialty. Mean Systolic BPdecreased by 4 mmHg following drug add-on but tended to rise thereafter.LimitationsLack of information on prescriber, and drug dosing.Conclusions: In patients with CKD and poor BP control, changes in antihypertensive drug prescriptions are common and relate to clinician preferences and patients’ tolerability. Sustainable reduction in Systolic BPafter add-on of a drug class is infrequently achieved

Urea levels and cardiovascular disease in patients with chronic kidney disease

International audienceABSTRACT Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 &lt;10.5, T2 10.5–15.1 and T3 ≥15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or non-atheromatous cardiovascular (CV) events and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data and medications. Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR