Causal relationship between basal metabolic rate and kidney function: a bidirectional two-sample mendelian randomization study.

Background: The relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR. Methods: In this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR. Results: We found that genetically predicted BMR was negatively related to eGFR, (ß= -0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (ß= -0.040, P = 0.002), weighted median (ß= -0.04, P= 5.35×10-11) and weighted mode method (ß= -0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (ß= -0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results. Conclusion: Genetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging.

L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions.

Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

Handgrip strength is associated with cognitive function in older patients with stage 3-5 chronic kidney disease: results from the NHANES.

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011-2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer's disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Renal and major clinical outcomes and their determinants after nephrectomy in patients with pre-existing chronic kidney disease: A retrospective cohort study.

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BACKGROUND: Insulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes. METHODS: The baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status. RESULTS: In 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status. CONCLUSIONS: In type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Speckle-Tracking: Incremental Role in Diastolic Assessment of Pediatric Patients with Chronic Kidney Disease. / Strain do Átrio Esquerdo pela Técnica de Speckle-Tracking: Contribuição para a Avaliação da Função Diastólica em Pacientes Pediátricos com Doença Renal Crônica.

BACKGROUND: Cardiovascular complications are the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). Echocardiographic assessment of diastolic function in CKD has been limited to spectral and tissue Doppler imaging, known to be less reliable techniques in pediatrics. Two-dimensional Speckle tracking echocardiography (2DST) derived left atrial (LA) strain has recently been confirmed as a robust measure of diastolic function. OBJECTIVES: To investigate LA strain role in diastolic assessment of children at different stages of CKD. METHODS: From February 2019 to July 2022, 55 CKD patients without cardiovascular symptoms and 55 controls were evaluated by standard and 2DST echocardiograms. The level of significance was set at 5% (p<0.05). RESULTS: Patients and controls had similar age [9.78 (0.89 - 17.54) vs. 10.72 (1.03 -18,44) years; p = 0.41] and gender (36M:19F vs. 34M:21F; p=0.84). There were 25 non-dialysis patients and 30 dialysis patients. Left ventricular ejection fraction was ≥ 55% in all of them. Comparing CKD and controls, LA reservoir strain was lower (48.22±10.62% vs. 58.52±10.70%) and LA stiffness index was higher [0.14 (0.08-0.48)%-1 vs. 0.11 (0.06-0.23) %-1]; p<0.0001. LV hypertrophy was associated with lower LA reservoir strain (42.05±8.74% vs. 52.99±9.52%), higher LA stiffness [0.23(0.11 - 0.48)%-1 vs. 0.13 (0.08-0.23) %-1 and filling indexes (2.39±0.63 cm/s x %-1 vs. 1.74±0.47 cm/s x %-1; p<0.0001. Uncontrolled hypertension was associated with lower LA reservoir strain (41.9±10.6% vs. 50.6±9.7; p=0.005). CONCLUSIONS: LA strain proved to be a feasible tool in the assessment of pediatric CKD patients and was associated with known cardiovascular risk factors.

FUNDAMENTO: As complicações cardiovasculares são a principal causa de morte em pacientes pediátricos com doença renal crônica (DRC). A avaliação ecocardiográfica da função diastólica na DRC tem se limitado à avaliação espectral por Doppler espectral e por Doppler tecidual, técnicas sabidamente menos confiáveis na pediatria. O strain do átrio esquerdo (AE) pela técnica do speckle tracking bidimensional (2DST) foi recentemente confirmada como uma medida robusta da função diastólica. OBJETIVOS: Investigar o papel do strain do AE na avaliação da função diastólica de crianças em diferentes estágios da DRC. MÉTODOS: De fevereiro de 2019 a julho de 2022, 55 pacientes com DRC sem sintomas cardiovasculares e 55 controles foram avaliados por ecocardiografia convencional e por ecocardiografia com 2DST. O nível de significância adotado foi de 5% (p < 0,05). RESULTADOS: Pacientes e controles tinham idade similares [9,78 (0,89 ­ 17,54) vs. 10,72 (1,03 ­18,44) anos; p = 0,41] e sexo (36M:19F vs. 34M:21F; p = 0,84) similares. Havia 25 pacientes não dialíticos e 30 pacientes dialíticos. A fração de ejeção do ventrículo esquerdo foi ≥ 55% em todos. Em comparação aos controles, os pacientes com DRC apresentaram strain de reservatório mais baixo (48,22±10,62% vs. 58,52±10,70%) e índice de rigidez do AE mais alto [0,14 (0,08­0,48)%-1 vs. 0,11 (0,06­0,23) %-1]; p<0,0001. A hipertrofia ventricular esquerda associou-se com um strain de reservatório mais baixo (42,05±8,74% vs. 52,99±9,52%), e valores mais altos de índice de rigidez [0,23 (0,11 ­ 0,48)%-1 vs. 0,13 (0,08­0,23) %-1 e de índice de enchimento do AE (2,39±0,63 cm/s x %-1 vs. 1,74±0,47 cm/s x %-1; p<0,0001). Hipertensão não controlada associou-se com strain de reservatório do AE mais baixo (41,9±10,6% vs. 50,6±9,7; p=0,005). CONCLUSÃO: O strain do AE mostrou-se uma ferramenta útil na avaliação de pacientes pediátricos com DRC e associado com fatores de risco cardiovasculares conhecidos.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study.

Introduction: Circadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed. Methods: A national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR <60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD. Results: A total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P < 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P < 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction < 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI = 1.33-3.58, P < 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P < 0.001) with per one increase of CircS components. Conclusion: CircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

A Cross-Sectional Study of Glomerular Hyperfiltration in Polycystic Ovary Syndrome.

Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time. In this comparative cross-sectional analysis, demographic, metabolic, and proteomic data from Caucasian women aged 18-40 years from a PCOS Biobank (137 with PCOS, 97 controls) was analyzed. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for inflammatory proteins, serum markers of chronic kidney disease (CKD), tubular renal injury markers, and complement system proteins. A total of 44.5% of the PCOS cohort had GH (eGFR ≥ 126 mL/min/1.73 m2 (n = 55)), and 12% (n = 17) eGFR ≥ 142 mL/min/1.73 m2 (super-GH(SGH)). PCOS-GH women were younger and had lower creatinine and urea versus PCOS-nonGH. C-reactive protein (CRP), white cell count (WCC), and systolic blood pressure (SBP) were higher in PCOS versus controls, but CRP correlated only with PCOS-SGH alone. Complement protein changes were seen between controls and PCOS-nonGH, and decay-accelerator factor (DAF) was decreased between PCOS-nonGH and PCOS-GSGH (p < 0.05). CRP correlated with eGFR in the PCOS-SGH group, but not with other inflammatory or complement parameters. Cystatin-c (a marker of CKD) was reduced between PCOS-nonGH and PCOS-GSGH (p < 0.05). No differences in tubular renal injury markers were found. A secondary cohort notes review of the biobank subjects 8.2-9.6 years later showed a reduction in eGFR: controls -6.4 ± 12.6 mL/min/1.73 m2 (-5.3 ± 11.5%; decrease 0.65%/year); PCOS-nonGH -11.3 ± 13.7 mL/min/1.73 m2 (-9.7 ± 12.2%; p < 0.05, decrease 1%/year); PCOS-GH (eGFR 126-140 mL/min/17.3 m2) -27.1 ± 12.8 mL/min/1.73 m2 (-19.1 ± 8.7%; p < 0.0001, decrease 2%/year); PCOS-SGH (eGFR ≥ 142 mL/min/17.3 m2) -33.7 ± 8.9 mL/min/17.3 m2 (-22.8 ± 6.0%; p < 0.0001, decrease 3.5%/year); PCOS-nonGH eGFR versus PCOS-GH and PCOS-SGH, p < 0.001; no difference PCOS-GH versus PCOS-SGH. GH was associated with PCOS and did not appear mediated through tubular renal injury; however, cystatin-c and DAF were decreased, and CRP correlated positively with PCOS-SGH, suggesting inflammation may be involved at higher GH. There were progressive eGFR decrements for PCOS-nonGH, PCOS-GH, and PCOS-SGH in the follow-up period which, in the presence of additional factors affecting renal function, may be clinically important in the development of CKD in PCOS.

Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

BACKGROUND: Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. OBJECTIVE: To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. DESIGN: Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. PATIENTS: A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. METHODS: The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. RESULTS: The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). CONCLUSION: The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Predicting chronic kidney disease progression with artificial intelligence.

BACKGROUND: The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3-5 CKD. METHODS: This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT. RESULTS: Three prediction models were developed-Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,- Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively. CONCLUSION: The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.

Aortic Stenosis and Renal Function: A Bidirectional Mendelian Randomization Analysis.

BACKGROUND: Large observational studies have demonstrated a clear inverse association between renal function and risk of aortic stenosis (AS). Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional 2-sample Mendelian randomization approach. METHODS AND RESULTS: We collected summary statistics for the primary analysis of chronic kidney disease (CKD) and AS from genome-wide association study meta-analyses including 480 698 and 653 867 participants, respectively. We collected further genome-wide association study summary statistics from up to 1 004 040 participants for sensitivity analyses involving estimated glomerular filtration rate (eGFR) derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. Inverse-variance weighted was the primary analysis method, with weighted-median, weighted-mode, Mendelian randomization-Egger, and Mendelian randomization-Pleiotropy Residual Sum and Outlier as sensitivity analyses. We did not find evidence of a causal relationship between genetically predicted CKD liability as the exposure and AS as the outcome (odds ratio [OR], 0.94 per unit increase in log odds of genetic liability to CKD [95% CI, 0.85-1.04], P=0.26) nor robust evidence of AS liability as the exposure and CKD as the outcome (OR, 1.04 per unit increase in log odds of genetic liability to AS [95% CI, 0.97-1.12], P=0.30). The sensitivity analyses were neutral overall, as were the analyses using eGFR derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. All positive controls demonstrated strong significant associations. CONCLUSIONS: The present study did not find evidence of a substantial effect of genetically predicted renal impairment on risk of AS. This has important implications for research efforts that attempt to identify prevention and treatment targets for both CKD and AS.

Clinical Implications of Estimating Glomerular Filtration Rate with Different Equations in Heart Failure Patients with Preserved Ejection Fraction.

INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and  < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or  < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.

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.

Development and validation of a race-agnostic computable phenotype for kidney health in adult hospitalized patients.

Standard race adjustments for estimating glomerular filtration rate (GFR) and reference creatinine can yield a lower acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence among African American patients than non-race adjusted estimates. We developed two race-agnostic computable phenotypes that assess kidney health among 139,152 subjects admitted to the University of Florida Health between 1/2012-8/2019 by removing the race modifier from the estimated GFR and estimated creatinine formula used by the race-adjusted algorithm (race-agnostic algorithm 1) and by utilizing 2021 CKD-EPI refit without race formula (race-agnostic algorithm 2) for calculations of the estimated GFR and estimated creatinine. We compared results using these algorithms to the race-adjusted algorithm in African American patients. Using clinical adjudication, we validated race-agnostic computable phenotypes developed for preadmission CKD and AKI presence on 300 cases. Race adjustment reclassified 2,113 (8%) to no CKD and 7,901 (29%) to a less severe CKD stage compared to race-agnostic algorithm 1 and reclassified 1,208 (5%) to no CKD and 4,606 (18%) to a less severe CKD stage compared to race-agnostic algorithm 2. Of 12,451 AKI encounters based on race-agnostic algorithm 1, race adjustment reclassified 591 to No AKI and 305 to a less severe AKI stage. Of 12,251 AKI encounters based on race-agnostic algorithm 2, race adjustment reclassified 382 to No AKI and 196 (1.6%) to a less severe AKI stage. The phenotyping algorithm based on refit without race formula performed well in identifying patients with CKD and AKI with a sensitivity of 100% (95% confidence interval [CI] 97%-100%) and 99% (95% CI 97%-100%) and a specificity of 88% (95% CI 82%-93%) and 98% (95% CI 93%-100%), respectively. Race-agnostic algorithms identified substantial proportions of additional patients with CKD and AKI compared to race-adjusted algorithm in African American patients. The phenotyping algorithm is promising in identifying patients with kidney disease and improving clinical decision-making.

Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective.

Over recent years, the nomenclature of non-alcoholic fatty liver disease has undergone significant changes. Indeed, in 2020, an expert consensus panel proposed the term "Metabolic (dysfunction) associated fatty liver disease" (MAFLD) to underscore the close association of fatty liver with metabolic abnormalities, thereby highlighting the cardiometabolic risks (such as metabolic syndrome, type 2 diabetes, insulin resistance, and cardiovascular disease) faced by these patients since childhood. More recently, this term has been further replaced with metabolic associated steatotic liver disease. It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments. However, comparable pediatric data remain limited. Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications, this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.