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

Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

peer reviewed[en] BACKGROUND: New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. METHODS: We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). RESULTS: Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. CONCLUSIONS: In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions

Extracellular Fluid Volume : Evolution and Prognostic value in Chronic Kidney Disease

Le volume extracellulaire (VEC) est étroitement régulé par les reins, via l’homéostasie sodée. Au cours de la maladie rénale chronique (MRC), il existe une altération de l’excrétion tubulaire de sodium, à l’origine d’une augmentation du VEC. L’évolution du VEC et sa valeur pronostique au cours de la MRC restent mal connues. En effet, si chez les patients dialysés chroniques, il est clairement établi que la surcharge hydro-sodée constitue un facteur indépendant de mortalité, les résultats des études pionnières menées chez des patients suivis pour une MRC restent controversés. L’analyse de l’impact de l’augmentation du VEC au cours de la MRC est un point important puisque celui-ci peut être modulé grâce à l’adaptation du traitement diurétique et de la consommation alimentaire de sodium. Par ailleurs, plusieurs applications cliniques – comme quantification du degré d’hypo ou d’hypervolémie, ou la mesure du débit de filtration glomérulaire – nécessitent une estimation précise du VEC théorique individuel. La valeur du VEC étant variable selon les caractéristiques anthropométriques et la composition corporelle, il donc est indispensable de développer un outil permettant d’estimer facilement le VEC théorique individuel. Les deux premiers axes d’études ont été menés chez les patients de la cohorte prospective hospitalière tricentrique NephroTest – cohorte qui inclut 2084 patients atteints de MRC de stade 1 à 5, de toutes étiologies – dont le VEC et le débit de filtration glomérulaire ont été mesurés par méthode de référence (i.e. volume de distribution et clairance d’un traceur exogène, respectivement). Dans la première partie, nous avons montré, grâce à l’utilisation de modèles de Cox cause-spécifiques, que le VEC constituait un facteur indépendant de mortalité, de progression de la MRC et d’insuffisance rénale chronique terminale. Dans la seconde partie, les résultats des modèles conjoints à effets aléatoires partagés avec prise en compte des risques compétitifs ont montré que le VEC augmentait avec la progression de la MRC, et que ces variations au cours du temps étaient associées aux risques de mortalité et d’insuffisance rénale chronique terminale. Dans la troisième partie, l’évaluation des différentes formules d’estimation du VEC théorique a montré que la précision et l’exactitude de ces dernières étaient faibles, questionnant leur utilisation en pratique clinique courante. Nous avons donc développé et validé une nouvelle équation d’estimation du VEC théorique, facilement utilisable en clinique ou en recherche, mais qui nécessite d’être validée à plus large échelle. L’ensemble de ces résultats corrobore le fait que le VEC est une cible thérapeutique très importante à considérer dans la prise en charge des patients suivis pour une MRC. Un outil d’estimation du VEC théorique facilement utilisable permettant de quantifier avec précision le degré d’hypervolémie reste nécessaire chez les patients ayant une MRC.Extracellular fluid volume (ECF) is tightly regulated by the kidneys, through sodium homeostasis. Chronic kidney disease (CKD) is characterized by an impairment of tubular sodium excretion, leading to ECF expansion. Change in ECF over time and its prognostic value remain poorly studied in CKD. Indeed, if several large-scaled studies have shown that fluid overload was a strong and independent risk factor for mortality in hemodialysis patients, results from pioneer studies conducted in non-dialysis CKD patients yielded conflicting results. Analysis of the impact of ECF during CKD is thus important in the clinical management of patients with CKD, as it may be corrected with diuretics and decreased sodium intake. Moreover, a precise and accurate estimation of the individual theoretical ECF is useful for several clinical settings, such as appreciation of how ECF may deviate from the normal condition, and glomerular filtration rate measurement (GFR) based on single-sample plasma clearance method. As ECF value varies according to anthropometric parameters, the development of a tool which allows estimation of individual theoretical ECF would be useful in clinical practice.The two first research topics have been conducted in patients from the prospective tricentric hospital-based NephroTest cohort – which included 2084 patients with CKD stage 1 to 5 of all etiologies – who underwent ECF and GFR measurements by gold standard methods (i.e. distribution volume and renal clearance of an exogenous tracer, respectively). In the first part, using cause-specific Cox models, we showed that ECF was an independent factor for mortality and end-stage kidney disease, and was associated with a faster GFR decline. In the second part, results from joint model for competing time-to-events with shared random effects showed that ECF increased over time in patients with CKD, and that this change in ECF was associated with the risks of mortality and end-stage kidney disease. In the third part, we showed that all ECF estimating equations displayed poor precision and accuracy, questioning their suitability in routine clinical practice. We thus developed and validated a new equation to estimate ECF. External validation in several cohorts including patients of extreme age and body mass index remains needed.All these results highlight the fact that ECF is an important therapeutic target in the clinical management of CKD patients. A readily applicable tool to accurately assess ECF excess in patients with CKD is needed

Le bilan du sodium : nouveaux aspects

International audienceLe sodium est majoritairement présent dans le compartiment liquidien extra-cellulaire. La quantité totale de sodium échangeable présente dans l’organisme détermine le volume extracellulaire et fait l’objet d’une régulation fine. Physiologiquement, l’homéostasie du sodium repose sur la capacité du rein à excréter les apports sodés alimentaires. La régulation de l’excrétion rénale du sodium est assurée par plusieurs systèmes de régulation – pro et anti-natriurétiques – capables d’agir localement ou à distance, et complémentaires par leur cinétique de mise en place et leurs mécanismes d’action. Ces dernières années, le modèle bi-compartimental « classique » a été entièrement remis en question par la découverte de stocks sodés dans le tissu sous-cutané ainsi qu’à la face interne des cellules endothéliales ainsi que par la mise en évidence de l’implication du système macrophagique (voie TonEBP – VEGF-C) dans l’homéostasie sodée sous-cutanée, indépendamment du rein. En démontrant une réalité beaucoup plus complexe sur la distribution du sodium dans l’organisme et l’implication du système immunitaire jusqu’alors insoupçonné, ces récentes découvertes pourraient permettre à terme, de mieux comprendre la physiologie, d’appréhender différemment certains mécanismes physiopathologiques voire d’ouvrir de nouvelles voies thérapeutiques à l’interface entre la physiologie et l’immunologie. Ces travaux scientifiques ont déjà des implications pratiques majeures puisqu’ils remettent en cause, entre-autres, la fiabilité du recueil urinaire des 24 heures pour quantifier des apports sodés alimentaires. Ainsi, dans cette revue, seront abordés successivement : le bilan du sodium et ses principaux systèmes de régulation, ainsi que la description des nouveaux aspects et leurs implications physiopathologiques, à la lumière des récentes découvertes sur le sujet

Vers de nouvelles cibles de traitement pour l’hypertension artérielle ?

La pression artérielle est un déterminant majeur du risque cardiovasculaire. La cible de pression artérielle à atteindre sous traitement antihypertenseur et la population à laquelle elle doit s’appliquer restent très débattues. Les cibles tensionnelles fixées par les sociétés savantes pourraient être revues à la baisse après la publication des résultats de l’essai multicentrique nord-américain SPRINT (systolic blood pressure intervention trial). L’analyse de l’applicabilité des résultats de l’étude SPRINT montre qu’ils sont complexes à appliquer à la population française et que les implications médicales et économiques pourraient être importantes

Delayed ileal perforation from sodium polystyrene sulfonate

International audienc

#4506 ACCURACY OF NOVEL GFR ESTIMATING EQUATIONS BASED ON CREATININE, CYSTATIN C OR BOTH IN ROUTINE CARE

peer reviewedAbstract Background and Aims New equations to estimate GFR (eGFR) based on creatinine, cystatin C or both have been developed in the last two years. A comprehensive comparison of their accuracy is currently lacking, particularly in cohorts not involved in their development or validation and among people with comorbid conditions. Method We included 6174 adults from the Stockholm Creatinine Measurements (SCREAM) project referred for plasma clearance of iohexol during 2011-2021, in whom we observed 9579 concurrent measurements of creatinine, cystatin C and iohexol clearance. We assessed the performance against measured GFR (mGFR) of eGFR equations proposed by the CKD-EPI collaboration (CKD-EPI 2009, 2012 and 2021), European Kidney Function Consortium (EKFC 2021 and 2023), and the revised Lund-Malmö (2011) and CAPA (2014) equations, which are used in Sweden. Bias was expressed as the median difference in eGFR minus mGFR, with negative biases indicating underestimation of mGFR. P30 described the percentage of individuals with eGFR within 30% of mGFR. Correct classification was defined as agreement of eGFR and mGFR categories using the KDIGO GFR categories. Subgroup analyses were conducted according to age, sex, BMI, eGFR, cancer, cardiovascular disease, diabetes, heart failure and liver disease. Results Mean age was 57 years, 46% of participants were female, mean mGFR was 62 mL/min/1.73 m2 and mean BMI was 26 kg/m2. Cardiovascular disease was the most common comorbid condition (30%), followed by liver disease (28%), diabetes (26%) and cancer (26%). Equations that used both creatinine and cystatin C had better performance than eGFR using each marker alone, regardless of the equation used; all such equations had small bias and P30 close to 90%. Among creatinine-based equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger overestimates of mGFR than EKFC 2021 and revised Lund-Malmö, with median biases of 5.6, 9.1, 2.7 and 0.2 mL/min/1.73 m2, respectively (Table 1). There were no meaningful differences in performance across eGFR equations based on cystatin C. Findings were consistent across subgroup analyses stratifying for comorbid conditions (Figure 1). Conclusion eGFR equations that combined information on creatinine and cystatin C performed better than equations based on creatinine or cystatin C alone in this Swedish cohort of routine referrals for plasma clearance of iohexol. There was larger variation in the performance of equations based on creatinine than cystatin C

Renal Outcome and New-Onset Renal and Extrarenal Dissections in Patients With Nontrauma Renal Artery Dissection Associated With Renal Infarction

International audienceWe aimed to compare the characteristics of the patients with renal infarction related to nontrauma renal artery dissection (RAD) with versus without an underlying vascular disease and report long-term renal and vascular outcomes, as well as new-onset renal and extra-RADs. Data from 72 consecutive patients with RAD referred to our Hypertension Unit between 2000 and 2015 were analyzed. Radiological data, including a systematic brain-to-pelvis computed tomography angiography, were independently reviewed. Three main causes of RAD were identified at the initial work-up: fibromuscular dysplasia (n=16); dissecting or aneurysmal multisite arterial disease (n=21) not linked to any known vascular disease; and isolated RAD (n=24) without any other arterial lesion. At diagnosis, patients (median age 46 [interquartile range, 40–53] years, 70.5% males, 26.2% preexisting hypertension, 65.6% smokers) had a median blood pressure of 138 (125–152)/87 (78–97) mm Hg. Estimated glomerular filtration rate was 81 (66–95) mL/min per 1.73 m 2 and 18% had renal impairment. Patients were treated with antiplatelet drugs (65.6%), anticoagulant (3.3%). A total of 11.5% underwent angioplasty. No clinical or biological difference was observed between the 3 groups. After 51 (19–92) months follow-up, blood pressure was reduced by 13 (0–29)/9 (3–18) mm Hg; 11.5% of patients had estimated glomerular filtration rate <60 mL/min per 1.73 m 2 . RAD evolved toward healing (67.2%), aneurysmal dilation (24.6%), or stenosis (8.2%). New-onset RAD was as frequent in dissecting or aneurysmal multisite arterial disease (23.8%) than in fibromuscular dysplasia (25%) group, whereas de novo extrarenal dissection was 6-fold more frequent in dissecting or aneurysmal multisite arterial disease (38.1%) than in fibromuscular dysplasia (6.3%) group. No new event occurred in patients with an initial diagnosis of isolated RAD. Initial diagnostic accuracy using thorough systematic exhaustive explorations of arterial sites helps to stratify the risk of new-onset dissection and adapt monitoring accordingly

A nationwide cohort study comparing the effectiveness of diuretics and calcium channel blockers on top of renin-angiotensin system inhibitors on chronic kidney disease progression and mortality

International audienceIt is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m2), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. We identified 5875 patients (median age 71 years, 64% men, median eGFR 26 ml/min per 1.73m2), of whom 3165 started a diuretic and 2710 a CCB. After a median follow-up of 6.3 years, 2558 MAKE, 1178 MACE and 2299 deaths occurred. Compared to CCB, diuretic use was associated with a lower risk of MAKE (weighted hazard ratio 0.87 [95% confidence interval: 0.77-0.97]), consistent across single components (KRT: 0.77 [0.66-0.88], over 40% eGFR decline: 0.80 [0.71-0.91] and eGFR under 15ml/min/1.73m2: 0.84 [0.74-0.96]). The risks of MACE (1.14 [0.96-1.36]) and all-cause mortality (1.07 [0.94-1.23]) did not differ between therapies. Results were consistent when modeling the total time drug exposure, across sub-groups and a broad range of sensitivity analyses. Thus, our observational study suggests that in patients with advanced CKD, using a diuretic rather than a CCB on top of RASi may improve kidney outcomes without compromising cardioprotection