Prevalence and factors associated with masked hypertension in chronic kidney disease.

OBJECTIVES: Optimal blood pressure (BP) control is key to prevent cardiovascular complications in patients with chronic kidney disease (CKD). We described the prevalence and factors associated with masked hypertension in CKD. METHODS: We analyzed 1113 ambulatory 24-h BP monitoring (ABPM) records of 632 patients referred for kidney function evaluation. Masked hypertension was defined as office BP less than 140/90 mmHg but daytime BP at least 135/85 mmHg or nighttime BP at least 120/70 mmHg. Factors associated with masked hypertension were assessed with mixed logistic regression models. RESULTS: At inclusion, 424 patients (67%) had controlled office BP, of whom 56% had masked hypertension. In multivariable analysis conducted in all visits with controlled office BP ( n  = 782), masked hypertension was positively associated with male sex [adjusted OR (95% confidence interval) 1.91 (1.16-3.27)], sub-Saharan African origin [2.51 (1.32-4.63)], BMI [1.11 (1.01-1.17) per 1 kg/m 2 ], and albuminuria [1.29 [1.12 - 1.47] per 1 log unit), and was negatively associated with plasma potassium (0.42 [0.29 - 0.71] per 1 mmol/L) and 24-h urinary potassium excretion (0.91 [0.82 - 0.99] per 10 mmol/24 h) as well as the use of renin-angiotensin-aldosterone (RAAS) blockers (0.56 [0.31 - 0.97]) and diuretics (0.41 [0.27 - 0.72]). CONCLUSION: Our findings support the routine use of ABPM in CKD, as more than half of the patients with controlled office BP had masked hypertension. Weight control, higher potassium intake (with caution in advanced CKD), correction of hypokalemia, and larger use of diuretics and RAAS blockers could be potential levers for better out-of-office BP control.

Rescaling creatinine makes GFR estimation equations generally applicable across populations - validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry.

OBJECTIVES: To make glomerular filtration rate (GFR) estimating equations applicable across populations with different creatinine generation by using rescaled serum creatinine (sCr/Q) where sCr represents the individual creatinine level and Q the average creatinine value in healthy persons of the same population. METHODS: GFR measurements (mGFR, plasma clearance of 51Cr-EDTA) were conducted in 964 adult Black Europeans. We established the re-expressed Lund-Malmö revised equation (r-LMR) by replacing serum creatinine (sCr) with rescaled creatinine sCr/Q. We evaluated the r-LMR equation based on Q-values of White Europeans (r-LMRQ-white; Q-values females: 62 µmol/L, males: 80 µmol/L) and Black Europeans (r-LMRQ-Black; Q-values females: 65 µmol/L, males: 90 µmol/L), and the European Kidney Function Consortium equation (EKFCQ-White and EKFCQ-Black) regarding bias, precision (interquartile range, IQR) and accuracy (percentage of estimates within ±10 % [P10] and ±30 % [P30] of mGFR). RESULTS: Median bias of r-LMRQ-White/r-LMRQ-Black/EKFCQ-White/EKFCQ-Black were -9.1/-4.5/-6.3/-0.9 mL/min/1.73 m2, IQR 14.7/14.5/14.5/15.6 mL/min/1.73 m2, P10 25.1 %/34.8 %/30.3 %/37.2 % and P30 74.2 %/84.1 %/80.6 %/83.6 %. The improvement of bias and accuracy when using proper Q-values was most pronounced in men. Similar improvements were obtained above and below mGFR 60 mL/min/1.73 m2 and at various age and BMI intervals, except for BMI<20 kg/m2 where bias increased, and accuracy decreased. CONCLUSIONS: GFR estimating equations may be re-expressed to include rescaled creatinine (sCr/Q) and used across populations with different creatinine generation if population-specific average creatinine concentrations (Q-values) for healthy persons are established.

Development and validation of a new equation based on plasma creatinine and muscle mass assessed by CT scan to estimate glomerular filtration rate: a cross-sectional study.

Background: Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods: The muscle mass-based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C-based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results: In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0-86.0] vs 51.5% (95% CI 39.0-64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0-55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7-66.0) for EKFC}. Difference in bias between Black and white subjects was -2.1 mL/min/1.73 m2 (95% CI -7.2 to 3.0), vs -8.4 mL/min/1.73 m2 (95% CI -13.2 to -3.6) for CKD-EPICr2021. Conclusion: MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Prevalence, treatment and determinants of obstructive sleep apnoea and its symptoms in a population-based French cohort.

Background: Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. Although the disorder has been well studied in selected high-risk populations, few data exist on its prevalence in the general population. We aimed to assess the prevalence and determinants of OSA in France. Methods: Data from participants of the French population-based CONSTANCES cohort aged 18-69 years at inclusion and being treated for sleep apnoea or screened for OSA in 2017 using the Berlin Questionnaire were analysed. Weighted analyses were performed to provide recent and representative results in the general population. Results: Among 20 151 participants, the prevalence of treated sleep apnoea was 3.5% (95% CI 3.0-3.9%). The prevalence of untreated subjects with a positive Berlin Questionnaire was 18.1% (95% CI 17.3-19.2%) for a total weighted prevalence of treated sleep apnoea or high risk of OSA of 20.9% (95% CI 20.0-21.9%). Regarding prevalence of OSA symptoms, it was 37.2% (95% CI 36.1-38.3%) for severe snoring and 14.6% (95% CI 13.8-15.5%) for hypersomnolence. In multivariable logistic regression analysis, male sex, age, previous cardiovascular events, smoking, low educational level, low physical activity and depressive symptoms were associated with having either treated sleep apnoea or a positive Berlin Questionnaire. Conclusion: In this large French population-based cohort, one in five participants had a high likelihood of OSA, whereas only 3.5% were treated for the disorder, suggesting major underdiagnosis in the general population. OSA diagnosis should be considered more often in people with risk factors such as depressive symptoms as well as unhealthy behaviours and socioeconomic conditions.

Comparison of 99mTc-DTPA and 51Cr-EDTA for glomerular filtration rate measurement with the continuous infusion method.

BACKGROUND: In late 2018, the production of 51Chromium-labelled ethylenediamine tetra-acetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for measuring glomerular filtration rate, was halted. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) has been validated for GFR measurement with a single bolus injection, a procedure not suitable in patients with extracellular compartment hyperhydration. In such cases, a bolus followed by continuous infusion of the tracer is required. The aim of this study was to evaluate whether 99mTc-DTPA with the infusion protocol can replace 51Cr-EDTA for GFR measurement. METHODS: We conducted a prospective single centre study during February and March 2019. All patients referred for GFR measurement received both radiotracers simultaneously: 51Cr-EDTA and 99mTc-DTPA bolus and continuous infusion were administered concomitantly through the same intravenous route. Over four and a half hours, plasma and urine samples were collected to calculate urinary and plasma clearance. RESULTS: Twenty-two patients were included (mean age 63.4 ± 17.5 years; 68% men). Mean urinary clearance of 51Cr-EDTA and 99mTc-DTPA was 52.4 ± 22.5 mL/min and 52.8 ± 22.6 mL/min, respectively (p = 0.47), with a mean bias of 0.39 ± 2.50 mL/min, an accuracy within 10% of 100% (95% CI 100; 100) and a Pearson correlation coefficient of 0.994. Mean plasma clearance of 51Cr-EDTA and 99mTc-DTPA was 54.8 ± 20.9 mL/min and 54.4 ± 20.9 mL/min, respectively (p = 0.61), with a mean bias of - 0.43 ± 3.89 mL/min, an accuracy within 10% of 77% (95% CI 59; 91) and a Pearson correlation coefficient of 0.983. CONCLUSIONS: Urinary and plasma clearance of 99mTc-DTPA can be used with the infusion protocol to measure GFR.

New developments and future prospects in the field of glomerular filtration rate estimation / Actualités et perspectives dans l'estimation du débit de filtration glomérulaire

Glomerular filtration rate (GFR) is estimated from equations based on serum or plasma concentrations of endogenous markers (creatinine and/or cystatin C), and demographic data (age, sex, ± ethnicity). These equations are accurate at the population level, but often inaccurate at the individual level. The creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation published in 2009 (CKD-EPIcr-2009), and the CKD-EPI equation published in 2012 based on creatinine and cystatin C, were recalibrated in 2021 to remove their dedicated race correction factors for black American subjects. All creatinine-based CKD-EPI equations overestimate true GFR in subjects younger than 30 years. The Full Age Spectrum (FAS) equation, applicable across the entire age spectrum (pediatrics to old age), solved this problem, but remained suboptimal at low GFR values. The European Kidney Function Consortium (EKFC) equation published in 2021 was an improvement of the FAS equation, which also includes the Q factor (median creatinine in the general population). EKFC is applicable across the age spectrum and is efficient at low and normal GFR values. The new creatinine-based CKD-EPI equation (CKD-EPIcr-2021) underestimates GFR in Black Americans and overestimates it in non-Black Americans. In European and African subjects, CKD-EPIcr-2021 overestimates true GFR and should not be adopted. The EKFC equation, which performs well in this population, also performs well in European Black subjects and in African subjects, provided dedicated Q factors are used.

Le débit de filtration glomérulaire (DFG) est estimé à partir d'équations prenant en compte la concentration sérique ou plasmatique de marqueurs endogènes (créatinine et/ou cystatine C) et des données démographiques (âge, sexe, ± origine ethnique). Ces équations sont justes à l'échelle populationnelle, mais fréquemment inexactes à l'échelle individuelle. L'équation Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), basée sur la créatinine, publiée en 2009 (CKD-EPIcr-2009), et l'équation CKD-EPI de 2012, basée sur la créatinine et la cystatine C, ont été recalibrées en 2021 afin d'éliminer leurs facteurs correctifs ethniques dédiés aux sujets Noirs américains. Toutes les équations CKD-EPI basées sur la créatinine surévaluent le DFG réel chez les sujets de moins de 30 ans. L'équation Full Age Spectrum (FAS), applicable sur tout le spectre d'âge (de la pédiatrie au grand âge), résolvait ce problème, mais restait suboptimale aux valeurs basses de DFG. L'équation European Kidney Function Consortium (EKFC) publiée en 2021 est une amélioration de l'équation FAS, qui inclut également le facteur Q (créatinine médiane en population générale). Elle est applicable sur tout le spectre d'âge, et performante aux valeurs basses et normales de DFG. La nouvelle équation CKD-EPI basée sur la créatinine (CKD-EPIcr-2021) sous-évalue le DFG chez les sujets Noirs américains et le surévalue chez les non-Noirs américains. Chez les sujets européens et africains, CKD-EPIcr-2021 surévalue le DFG réel et ne doit pas être adoptée. L'équation EKFC, qui est performante dans cette population, l'est aussi chez les sujets européens Noirs et les Africains, à condition d'utiliser des facteurs Q dédiés.

Optimal or standard control of systolic and diastolic blood pressure across risk factor categories in patients with chronic coronary syndromes.

AIMS: Guidelines have lowered blood pressure (BP) targets to <130/80 mmHg. We examined the benefit of intensive control for each BP component, vs. the burden of other modifiable risk factors, in patients with chronic coronary syndromes (CCS). METHODS AND RESULTS: The CLARIFY registry (ISRCTN43070564) enrolled 32 703 patients with CCS, from 2009 to 2010, with a 5-year follow-up. Patients with either BP component below European guideline safety boundaries (120/70 mmHg) were excluded, leaving 19 167 patients (mean age: 63.8 ± 10.1 years, 78% men) in the present analysis. A multivariable-adjusted Cox proportional hazards model showed a gradual increase in cardiovascular risk (cardiovascular death, myocardial infarction, or stroke) when the number of uncontrolled risk factors (active smoking, no physical activity, low-density lipoprotein cholesterol ≥100 mg/dL, and diabetes with glycated haemoglobin ≥7%) increased [adjusted hazard ratio (HR): 1.34; 95% confidence interval (CI): 1.17-1.52, 1.65 (1.40-1.94), and 2.47 (1.90-3.21) for 1, 2, and 3 or 4 uncontrolled risk factors, respectively, vs. 0], without significant interaction with BP. Although uncontrolled systolic (≥140 mmHg) and diastolic (≥90 mmHg) BP were both associated with higher risk than standard BP, standard BP was associated with higher risk than optimal control for only the diastolic component (adjusted HR: 1.08; 95% CI: 0.94-1.25 for systolic BP 130-139 vs. 120-129 mmHg and 1.43; 95% CI: 1.27-1.62 for diastolic BP 80-89 vs. 70-79 mmHg). CONCLUSIONS: Our results suggest that the optimal BP target in CCS may be ≤139/79 mmHg and that optimizing the burden of other risk factors should be prioritized over the further reduction of systolic BP.

We aimed to compare the benefit associated with strict vs. standard control of blood pressure with the potential benefit of controlling other modifiable risk factors in patients with chronic coronary syndromes (CCS).Our analysis conducted in nearly 20 000 patients from the CLARIFY registry (a prospective international cohort of patients with CCS) showed that the benefit associated with strict blood pressure (BP) control (BP < 130/80 mmHg) was marginal and only driven by the diastolic component of blood pressure, whereas having one or more uncontrolled other risk factors was associated with a gradually increasing risk, for all underlying BP levels.Patients with CCS should be treated to achieve BP <140/80 mmHg. However, our results suggest that optimizing the burden of other risk factors (lipid-lowering therapy, exercise, smoking cessation, diabetes control) may need to be prioritized before considering further reduction of systolic BP.

Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex.

BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).

Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa.

BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

Clinically relevant urine creatinine underestimation in the low concentration range on the Siemens Dimension Vista®.

While considerable efforts have been accomplished to standardize the measurement of plasma creatinine (PCr), urine creatinine (UCr) has not been subject to the same scrutiny. UCr is importantly used when measuring biomarkers in spot urines, to assess urine output and variable dilution of urine samples. Here, we report underestimation of Jaffe UCr measurements on the Siemens Dimension Vista® analyzer, critically affecting samples with UCr ≤2 mmol/L. We demonstrate that this error is caused by automatic urine pre-dilution by the Vista's «urine mode¼, and that UCr measured in «plasma mode¼ without pre-dilution does not present this error. In the absence of a comprehensive solution proposed by Siemens, we propose simple formulae that can be easily implemented in a laboratory to correct these low UCr measurements. Importantly, the observed UCr underestimation can significantly influence reported results for biomarkers/UCr ratios measured in spot urine. Indeed, these results can be overestimated up to +84.4 % before correction using our formulae. This can sometimes lead to misclassification according to clinical thresholds, e.g. Kidney disease: improving global outcomes (KDIGO) guidelines for urine albumin/creatinine. This highlights the need for every clinical laboratory to assess the detection limits of their assays, including for lesser-discussed parameters such as UCr. Indeed, the error we reported here may affect other urine assays performing systematic urine pre-dilution and could have significant repercussions on the clinical management of patients.

Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria.

Introduction: Lithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output. Methods: Prospective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in n = 119), and measured glomerular filtration rate (mGFR). Maximal urine osmolality (MaxUosm) was the highest level during the DDAVP test. Results: Of the individuals, 21% displayed polyuria (>3 l/d), but 55% displayed elevated fasting vasopressin level (>5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for >10 years. MaxUosm was >600 mOsm/KgH2O in 128 patients (59%), among which vasopressin was increased in 51%, associated with higher lithium dose (950 [750-1200] vs. 800 [500-1000] mg/d, P < 0.001). All patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (ß 0.49 ± 0.17, P = 0.005), female sex (ß -359 ± 123, P = 0.004), daily osmolar intake (ß 2.21 ± 0.24, P < 0.001), MaxUosm (ß -2.89 ± 0.35, P < 0.001), and plasma vasopressin level (ß 10.17 ± 4.76, P = 0.03). Conclusion: Higher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients.

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

Introduction: 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.

MRI-based kidney radiomic analysis during chronic lithium treatment.

BACKGROUND: Lithium therapy during bipolar disorder is associated with an increased risk of chronic kidney disease (CKD) that is slowly progressive and undetectable at early stages. We aimed at identifying kidney image texture features as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomics of T2-weighted magnetic resonance imaging (MRI). METHODS: One hundred and eight patients treated with lithium were evaluated including mGFR and kidney MRI, with T2-weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect an mGFR <60 ml/min/1.73 m². The texture index was validated using a training and a validation cohort. RESULTS: Texture analysis index was able to detect an mGFR decrease, with an AUC of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 [42-66] vs. 46 [34-54] years, p = .001), with longer treatment duration (10 [3-22] vs. 6 [2-10] years, p = .02) and a lower mGFR (66 [46-84] vs. 83 [71-94] ml/min/1.73m², p < .001). Texture analysis index was independently and negatively associated with age (ß = -.004 ± 0.001, p < .001), serum vasopressin (-0.005 ± 0.002, p = .02) and lithium treatment duration (-0.01 ± 0.003, p = .001), with a significant interaction between lithium treatment duration and mGFR (p = .02). CONCLUSIONS: A renal texture index was developed among patients treated with lithium associated with a decreased mGFR. This index might be relevant in the diagnosis of lithium-induced renal toxicity.

Prevalence of diabetes and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities.

BACKGROUND: In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. METHODS AND RESULTS: CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009-2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. CONCLUSION: In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. CLINICALTRIALS IDENTIFIER: ISRCTN43070564.