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BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Background and Purpose: The ryanodine receptor 2 (RyR2) is present in both the heart and kidneys, and plays a crucial role in maintaining intracellular Ca2+ homeostasis in cells in these organs. This study aimed to investigate the impact of M201‐A on RyR2, as well as studying its effects on cardiac and renal functions in preclinical and clinical studies. Experimental Approach: Following the administration of M201‐A (1,4‐benzothiazepine‐1‐oxide derivative), we monitored diastolic Ca2+ leak via RyR2 and intracellular Ca2+ concentration in isolated rat cardiomyocytes and in cardiac and renal function in animals. In a clinical study, M201‐A was administered intravenously at doses of 0.2 and 0.4 mg·kg−1 once daily for 20 min for four consecutive days in healthy males, with the assessment of haemodynamic responses. Key Results: In rat heart cells, M201‐A effectively inhibited spontaneous diastolic Ca2+ leakage through RyR2 and exhibited positive lusi‐inotropic effects on the rat heart. Additionally, it enhanced natriuresis and improved renal function in dogs. In human clinical studies, when administered intravenously, M201‐A demonstrated an increase in natriuresis, glomerular filtration rate and creatinine clearance, while maintaining acceptable levels of drug safety and tolerability. Conclusions and Implications: The novel drug M201‐A inhibited diastolic Ca2+ leak via RyR2, improved cardiac lusi‐inotropic effects in rats, and enhanced natriuresis and renal function in humans. These findings suggest that this drug may offer a potential new treatment option for chronic kidney disease and heart failure. [ABSTRACT FROM AUTHOR]

Objectives Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). Methods In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n  = 5, mild RI: n  = 8, moderate RI: n  = 9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% f T > MIC (minimal inhibitory concentration). Results Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0–12h = 1143 h.mg/L and % f T > MIC = 68%), followed by mild RI patients (median AUC0–12h = 918 h.mg/L and % f T > MIC = 34%), and the lowest in those with healthy kidney function (median AUC0–12h = 692 h.mg/L and % f T > MIC = 26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate < 60 mL/min and MIC ≤ 8 mg/L. Conclusion The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and effectiveness of endoscopic treatments with Allium® metal ureteric stent (AMUS) for ureteric strictures after kidney transplantation (KT). Patients and Methods: In a prospective manner, we gathered clinical data from 68 patients who underwent endoscopic treatments with AMUS for ureteric strictures after KT between January 2019 and March 2022. The definition of surgical success was the unobstructed drainage of the AMUS, or in cases where there was AMUS migration, occlusion or encrustation and subsequently removed, there is no worsening of renal hydronephrosis in the patient during the follow‐up period. Results: Based on the specific circumstances of the ureteric strictures, three distinct types of surgery were selected for treatment. The overall success rate of endoscopic treatments for ureteric strictures following KT was 90% (61/68) during a follow‐up period of 1 year. Surgical complications included haematuria (18%), pain (10%), urinary tract infections (7.4%), and lower urinary tract symptoms (7.4%). The incidences of stent migration, occlusion, and encrustation were 10%, 2.9%, and 1.5%, respectively. Postoperatively, significant improvements were observed in various parameters. At 1 month after surgery, there was a notable decrease in blood creatinine levels (105.5 vs 90.4 mol/L), urea nitrogen levels (6.6 vs 5.4 mmol/L), and hydronephrosis volume (64.4 vs 43.9 mL). Additionally, the serum estimated glomerular filtration rate increased from 49.5 to 64.4 mL/min/1.73 m2. The follow‐up results of patients at 1 year after surgery were similar to those observed at 1 month after surgery. Conclusions: Systemic endoscopic treatments with AMUS were found to be safe and effective for ureteric strictures after KT with short‐term follow‐ups. This technique offers a novel option for the treatment of post‐KT strictures. [ABSTRACT FROM AUTHOR]

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability. [ABSTRACT FROM AUTHOR]

Aims: Although there are various model‐based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)‐based model for predicting VCM trough concentration in adult PJI patients. Methods: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). Results: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. Conclusion: The proposed ML‐based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment. [ABSTRACT FROM AUTHOR]

The article describes the case of a 59-year old Japanese man diagnosed with cerebellar cognitive affective syndrome (CCAS) caused by cerebellar atrophy associated with Wallerian degeneration after pontine haemorrhage. The patient demonstrated psychiatric symptoms, slow gait, configuration apraxia, cognitive and motor decline, decline in intelligence quotient and function. Symptoms of CCAS include motor deficits, decreased blood flow in the posterior cerebellar lobes and functional impairment.

Aim: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. Research design and methods: In this post‐hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%‐7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow‐up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini‐mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. Results: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini‐mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: −0.57 in the Rey auditory verbal learning test, 95% CI: −1.09, −0.05, Cohen's d: −0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p <.05. Conclusions: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD. [ABSTRACT FROM AUTHOR]

Aim: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long‐term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Methods: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end‐stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. Results: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%–30% decrease, 14.4% (n = 1199) experienced a 0%–30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin‐to‐creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: −3.6 ± 10.9, −2.0 ± 9.5, −1.1 ± 8.6, and −0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61–4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48–0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. Conclusion: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long‐term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Aims: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM). Materials and Methods: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow‐up visit, or end‐stage kidney disease. Results: During a median follow‐up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69–0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59–0.88) from baseline to 1‐year follow‐up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58–1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4‐year changes in body composition. Conclusions: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM. [ABSTRACT FROM AUTHOR]

Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non‐linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model‐based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two‐compartment model with first‐order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) as a covariate on clearance reduced inter‐individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD‐EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L. [ABSTRACT FROM AUTHOR]

Summary: Background: Withholding or continuing angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers peri‐operatively in non‐cardiac surgery remains controversial as they may result in intra‐operative hypotension and postoperative organ damage. Methods: We included patients prescribed angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers who underwent surgical procedures > 1 h duration under general or spinal anaesthesia from January 2012 to June 2022 in a single centre. We categorised patients by whether these drugs were withheld for 24 h before surgery. We evaluated the association of withholding these drugs before non‐cardiac surgery with creatinine concentrations that increased ≥ 26.4 μmol.l‐1 in the first 48 postoperative hours (acute kidney injury). We also analysed changes in creatinine concentrations and estimated glomerular filtration rates. Results: Angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers were withheld in 24,285 of 32,933 (74%) patients and continued in 8648 (26%) patients. We used propensity scores for drug discontinuation to match 8631 patient pairs who did or did not continue these drugs: acute kidney injury was recorded for 1791 (21%) patients who continued these drugs vs. 1587 (18%) who did not (OR (95%CI) 1.16 (1.08–1.25), p < 0.001). Intra‐operative hypotension was recorded for 3892 (45%) patients who continued drugs vs. 3373 (39%) patients who did not (OR (95%CI) 1.28 (1.21–1.36), p < 0.001). Continuing drugs was independently associated with a mean increase in creatinine of 2.2 μmol.l‐1 (p < 0.001) and a mean decrease in estimated glomerular filtration rate of 1.4 ml.min.1.73 m‐2 (p < 0.001). Conclusions: Continuing angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers 24 h before non‐cardiac surgery was associated with intra‐operative hypotension and postoperative acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. Methods: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3–5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. Results: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. Conclusions: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (− 0.13 ± 1.21 vs. − 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β − 7.5 × 10−6, CI − 1.2 × 10−5, − 3 × 10−6, p = 0.001) and incident cases of NS (vs. prevalent) (β − 1.1, CI − 2.22, − 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time. Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score. [ABSTRACT FROM AUTHOR]

Background: Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses. Methods: In this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients. Results: Out of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5–8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up. Conclusions: Most patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Individuals with congenital solitary functioning kidney (SFK) are at an increased risk of kidney damage. According to some studies, the risk is higher in unilateral kidney agenesis (UKA) than in unilateral multicystic dysplastic kidney (UMCDK). We hypothesized that with early detection of children with UKA and UMCDK, there would be no difference in the presence of hypertension, proteinuria, and reduced glomerular filtration rate (GFR) between UKA and UMCDK. Methods: Based on a long-term follow-up protocol, we evaluated a cohort of 160 children followed from birth for SFK (84 with UKA and 76 with UMCDK) detected by prenatal or routine neonatal ultrasound screening. Hypertension, proteinuria, and reduced GFR were monitored as markers of kidney damage. We compared the characteristics and outcomes of the subgroups of children with UKA and UMCDK. Results: GFR was reduced in 42 (26.2%) children, of whom 41 showed only mild reduction. Hypertension and proteinuria were found in 22 (13.8%) and 14 (8.8%) children, respectively. Combined kidney damage was present in 57 (35.6%) children. The UMCDK and UKA subgroups differed in GFR at final examination, with UMCDK patients being significantly more likely to have normal GFR compared to UKA patients (82% vs. 67%; p = 0.039). Conclusions: One third of the children showed signs of SFK damage, albeit mild. Patients with UKA had reduced GFR significantly more often than those with UMCDK, but did not differ in the rates of hyperfiltration injury or congenital anomalies of the kidneys and urinary tract (CAKUT) in SFK. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the efficacy and safety of belimumab combined with the standard regimen in treating children with active lupus nephritis. This single-center, retrospective cohort study used clinical data of children with newly active lupus nephritis hospitalized in the Department of Nephrology between December 2004 and February 2023. Patients were divided into a belimumab or traditional treatment group according to whether or not they received belimumab. Renal remission and recurrence rates and glucocorticoid dose were compared between groups. Forty-seven children (median age 11 years) were enrolled, including 30 and 17 children in the traditional treatment and belimumab groups, respectively. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) score of children in the belimumab group (23.59 ± 7.78) was higher than that in the traditional treatment group (19.13 ± 6.10) (P = 0.035). The two groups showed no significant difference in the frequency of pyuria, gross hematuria, and the levels of 24-h proteinuria and estimated glomerular filtration rate. The complement C3/C4 in the belimumab group recovered faster than that in the traditional treatment group (P < 0.05). There were no between-group differences in the complete renal remission rate at 6 or 12 months (P = 0.442, P = 0.759). There were no between-group differences in 1-year recurrence rate (P = 0.303). Furthermore, 6 and 12 months after treatment, glucocorticoid doses were lower in the belimumab than the traditional treatment group (17.87 ± 6.96 mg/d vs. 27.33 ± 8.40 mg/d, P = 0.000; 10.00 (5.3) mg/d vs. 13.75 (10.0) mg/d, P = 0.007), respectively. Conclusion: With an equivalent renal remission rate, belimumab combined with the standard traditional regimen might promote the tapering of glucocorticoids, and the incidence of adverse events is low. What is known: • Belimumab is documented as an adjunctive treatment with systemic lupus erythematosus (c-SLE) LN with efficacy. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. What is new: • This single-center, retrospective cohort study evaluated the efficacy and safety of belimumab combined with the standard regimen in treating children with proliferative LN. • Belimumab combined with the standard traditional treatment might promote the tapering of glucocorticoids, while exhibiting a low occurrence of adverse events. [ABSTRACT FROM AUTHOR]

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3–5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976. Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges. What is Known? • Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD. • Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD. What is New? • Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group. • Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR. • Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. RESEARCH DESIGN AND METHODS: Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10–18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. RESULTS: Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (−5.8 vs. −0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). CONCLUSIONS: Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures. RESULTS: At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF–to–MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]). CONCLUSIONS: Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D. [ABSTRACT FROM AUTHOR]

Background and Aims: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase‐associated lipocalin (u‐NGAL), urinary beta‐2‐microglobulin (u‐B2M), urinary osteopontin (u‐OPN), urinary trefoil factor 3 (u‐TFF3) and urinary Cystatin C (u‐Cys). Methods: This is a case‐control study investigating the following urinary biomarkers of tubular damage: u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys, in patients with mild acute hyperbilirubinemia. Seventy‐four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. Results: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u‐NGAL, u‐B2M, u‐OPN, u‐TFF3 and u‐Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u‐NGAL values (OR = 3.8, 95% CI 1.07–13.5, p =.03) and u‐B2M (OR = 9.4, 95% CI 2.3–38.9, p =.0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. Conclusions: This study demonstrated increased urinary biomarkers of tubular damage (u‐NGAL, u‐B2M, u‐OPN, u‐TFF3, and u‐Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology). [ABSTRACT FROM AUTHOR]

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management. [ABSTRACT FROM AUTHOR]

Background Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3 / COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 -related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4 and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3 / COL4A4 genes is assessed in this study. Methods We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, estimated glomerular filtration rate (eGFR) and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. Results Half of the individuals with P/LP variants in COL4A3 / COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (P  < .001). No association was found between KC and proteinuria, sex or causative gene. Conclusions Individuals with COL4A3 / COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals. [ABSTRACT FROM AUTHOR]

Background Pulmonary haemorrhage with hypoxia caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) Trial. Methods A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan. Results Eight patients (62.5% female), median age 64 years (range 17–80), seven with kidney involvement, median estimated glomerular filtration rate (eGFR) 11 (range 5–99) mL/min/1.73 m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were myeloperoxidase-ANCA and three proteinase 3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6–60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received 2 months of daily extracorporeal membrane oxygenation therapy. Following the initiation of avacopan after a median of 10 days (range 2–40), pulmonary haemorrhage resolved in all patients, even the two who had 1 month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after 1 month, the median prednisolone dose was 5 mg/day (range 0–50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after 3 months due to neutropenia. All patients survived and no re-hospitalization occurred. Conclusion We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. Methods and results: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p =.008). Conclusions: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous. [ABSTRACT FROM AUTHOR]

Background: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. Methods: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46–69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. Results: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02–20.6), p = 047, 0.95 (0.94–0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4–5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. Conclusions: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation. [ABSTRACT FROM AUTHOR]

Background Glomerular filtration rate (GFR) estimation by Gates protocol using the gamma camera for diethylenetriaminepentaacetic acid (DTPA) dynamic renography has not compared well with the gold standard GFR by plasma sampling method. This is because depth of the kidneys is generally not considered. Our aim was to study whether manual depth correction using the skin to middle of kidney distance in lateral view and posterior aspect-lateral posterior method would reduce the bias in the Gates GFR as compared with the gold standard. Materials and Methods Retrospective study of 27 adult prospective renal donors who underwent GFR by plasma sampling and DTPA dynamic renography at Inlaks and Budhrani Hospital, Pune, Maharashtra, India between January 2022 and April 2023. The entire data was statistically analyzed using Statistical Package for Social Sciences (SPSS ver 21.0, IBM Corporation, United States) for MS Windows. Results There is no significant agreement between plasma sampling versus gamma camera method and plasma sampling versus lateral posterior method for depth correction for GFR measurements; however, the evidence of systemic bias is lower for the gamma camera method compared with the lateral posterior method for depth correction as against the plasma sampling method. Conclusion The lateral posterior method for depth correction while using the gamma camera-based Gates protocol is not a reliable method for depth correction in the western Indian adult population with preserved renal function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of diabetes retinopathy and evaluate the factors influencing its occurrence both at the onset of type 2 diabetes (T2D) and three years into its duration. Design: Retrospective population-based study. Setting: Data was retrieved from Regional Healthcare Information Platform in Region Halland 2016–2020. Subjects: Patients 35-75 years old in Region Halland receiving first-time diabetes diagnosis according to ICD-code E11-14 in 2016–17. The total cohort consisted of 1659 patients. Main outcome measures: The main outcome measure of the study was the occurrence of diabetes retinopathy at onset and within three years from the diabetes diagnosis. Multivariate logistic regression analysis was conducted for diabetes retinopathy at onset and within three years, adjusted for age, gender, comorbidities, levels of HbA1c, cholesterol, kidney functional and blood pressure. Results: At onset, there were 12% with diabetes retinopathy and after three years, 32% of the patients had developed diabetes retinopathy. In the study cohort, 71 of patients who were examined with fundus photography within three years after onset, and 8% had had dietary recommendation without pharmacotherapy. High HbA1c levels, blood pressure values and impaired renal function already at onset were associated with development of diabetes retinopathy at onset and this association persisted after three years. The odds ratio for diabetes retinopathy was increased adjusted for HbA1c elevations, renal impairment, and increased blood pressure at index and when adjusted for these variables three years from index. Conclusion: These findings indicate that the risk of developing diabetes retinopathy is present early on at onset and within the first three years of diabetes diagnosis. This highlights the importance of promptly regulating glucose- and blood-pressure levels and follow up kidney dysfunction to mitigate the risk of diabetes retinopathy. KEY POINTS: Among patients with type 2 diabetes, 12% had developed diabetes retinopathy already at onset. Among patients with type 2 diabetes, one-third had developed diabetes retinopathy after three years from onset. The presence of diabetes retinopathy already at diabetes onset, was associated with elevated HbA1c levels, renal impairment and elevated blood pressure. Diabetes retinopathy three years after the onset of the disease, was associated with increased HbA1c levels, high blood pressure, and renal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. Aims: (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. Methods: Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. Results: All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. Discussion: Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. Trial Registration: ClinicalTrials.gov NCT01144338 and NCT00790205 [ABSTRACT FROM AUTHOR]

Vancomycin continuous infusion (CI) has suggested benefits over intermittent infusion: reduced nephrotoxicity, higher target attainment, and simpler therapeutic drug monitoring (TDM). Empiric dosing regimens range from 30–60 mg/kg/day and it is unclear which regimen results in optimal exposure. This study evaluates whether a dosing regimen of 45 mg/kg/day after a 20 mg/kg loading dose for patients with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min results in adequate exposure. We retrospectively analyzed plasma concentrations from patients treated with vancomycin CI as routine clinical care between February and October 2021. Patients under 18 years old, with renal replacement therapy, reduced creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration < 50 mL min/1.73 m2) or outpatient antibiotic therapy were excluded. Dose, renal function, and blood draw procedures were assessed for each measured vancomycin sample. Initially, 121 samples were included. Subsequently, 7 samples, 6 of which with concentrations ≥ 40 mg/L, were verified to be incorrectly drawn and excluded. With doses of 40–50 mg/kg/day concentrations ranged from 18.4–61.0 mg/L. Only 25% were within the target window of 17–25 mg/L and 15% were ≥ 40 mg/L. Supratherapeutic concentrations were observed in 89% of samples from patients dosed 40–60 mg/kg/day with eGFR 50–80 mL/min. Concluding, an empiric dosing regimen of 45 mg/kg results in too high vancomycin exposure and thus we recommend lower doses and differentiation according to renal function. Additionally, when measuring concentrations over 40 mg/L incorrect sampling must be excluded before dose adjustment and the large variability in exposure between patients, warrants the need for swift TDM. [ABSTRACT FROM AUTHOR]

Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P <.001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy. [ABSTRACT FROM AUTHOR]

Since 2020, there have been changes in Food and Drug Administration guidance and in recommendations by national organizations with a focus on kidney diseases pertaining to the choice of equations used to estimate creatinine clearance and glomerular filtration rate in patients with renal impairment. This includes a recommendation by the National Kidney Foundation to avoid the use of the Cockcroft-Gault equation for drug dosing in patients with renal impairment. This commentary provides an overview of recent recommendations concerning kidney function assessment that have important implications for drug dosing in patients with renal impairment and provides suggestions for implementing these recommendations. [ABSTRACT FROM AUTHOR]

Objective: The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM). Methods: T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves. Results: The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium–glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61). Conclusions: Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention.Participants with type 2 diabetes from the randomized, double‐blind, placebo‐controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m2]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time.Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7.This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D. [ABSTRACT FROM AUTHOR]

Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in the VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) study. Fragile patients are at heightened risk for ischemic and bleeding events. The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD. Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m2). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding. Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65). Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population. [ABSTRACT FROM AUTHOR]

The exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors. Apparently healthy Black and White sexes were included (aged 20–30 years) and categorised by the presence or absence of risk factors, i.e., obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036), CVD risk clusters (i.e. presenting with 1 CVD risk factor (N = 344), 2 CVD risk factors (N = 360) and 3 + CVD risk factors (N = 332)) and the control group (N = 166). eGFR was calculated with CKD-EPI equations. A targeted metabolomics approach using liquid chromatography-tandem mass spectrometry was used to measure amino acids and acylcarnitines. Lower cystatin C-based eGFR were indicated in the CVD risk group, 2 and 3 + CVD risk clusters compared to the control group (all P ≤ 0.033). In the CVD risk group, eGFR associated positively with histidine, lysine, asparagine, glycine, serine, glutamine, dimethylglycine, threonine, alanine, creatine, cystine, methionine, tyrosine, pyroglutamic acid, leucine/isoleucine, aspartic acid, tryptophan, glutamic acid, free carnitine, acetylcarnitine, propionylcarnitine, isovalerylcarnitine, octanoylcarnitine and decanoylcarnitine (all P ≤ 0.044), with similar results found in the CVD risk clusters, particularly the 2 CVD risk cluster. eGFR was positively associated with metabolites linked to aromatic amino acid and branched-chain amino acid metabolism, energy metabolism and oxidative stress. These findings may indicate altered reabsorption of these metabolites or altered metabolic regulation to preserve renal health in the setting of CVD risk factors at this young age without established CVD. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) significantly increases morbidity and mortality following cardiac surgery, especially in patients with pre-existing renal impairments. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and dysfunction, conditions often exacerbated during cardiac surgery and prevalent in chronic kidney disease (CKD) patients. Elevated NT-proBNP levels can indicate underlying cardiac strain, hemodynamic instability and volume overload. This study evaluated the association between perioperative changes in NT-proBNP levels and the incidence of AKI in this particular patient group. Methods: This retrospective study involved patients with impaired renal function (eGFR 15–60 ml/min/1.73 m²) who underwent cardiac surgery from July to December 2022. It analyzed the association between the ratio of preoperative and ICU admittance post-surgery NT-proBNP levels and the development of AKI and AKI stage 2–3, based on KDIGO criteria, using multivariate logistic regression models. Restricted cubic spline analysis assessed non-linear associations between NT-proBNP and endpoints. Subgroup analysis was performed to assess the heterogeneity of the association between NT-proBNP and endpoints in subgroups. Results: Among the 199 participants, 116 developed postoperative AKI and 16 required renal replacement therapy. Patients with AKI showed significantly higher postoperative NT-proBNP levels compared to those without AKI. Decreased baseline eGFR and increased post/preoperative NT-proBNP ratios were associated with higher AKI risk. Specifically, the highest quantile post/preoperative NT-proBNP ratio indicated an approximately seven-fold increase in AKI risk and a ninefold increase in AKI stage 2–3 risk compared to the lowest quantile. The area under the receiver operating characteristic curve for predicting AKI and AKI stage 2–3 using NT-proBNP were 0.63 and 0.71, respectively, demonstrating moderate accuracy. Subgroup analysis demonstrated that the positive association between endpoints and logarithmic transformed post/preoperative NT-proBNP levels was consistently robust in subgroup analyses stratified by age, sex, surgery, CPB application, hypertension, diabetes status and fluid balance. Conclusion: Perioperative NT-proBNP level changes are predictive of postoperative AKI in patients with pre-existing renal deficiencies undergoing cardiac surgery, aiding in risk assessment and patient management. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effectiveness of burosumab therapy in children with X-Linked Hypophosphatemia (XLH). Materials and methods: We systematically reviewed literature from PubMed, Web of Science, The Cochrane Library, and Embase up until January 2024, using EndNote Web for study organization. The Newcastle-Ottawa scale guided quality assessment, while Revman software was used for data analysis and visualization. Study selection, quality evaluation, and data aggregation were independently performed by three researchers. Results: The meta-analysis encompassed ten studies, including eight cohort studies that examined burosumab's impact pre- and post-administration, and two randomized controlled trials comparing burosumab to standard therapy. The evidence from this review suggests burosumab's superiority in managing XLH in pediatric populations, particularly in improving key biochemical markers including 1,25-dihydroxyvitamin D (1,25-(OH)2D), phosphorus, and alkaline phosphatase (ALP), alongside improvements in the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), and significant skeletal improvements as indicated by the rickets severity score (RSS) and the 6-minute walk test (6MWT). However, the long-term safety and effects, including height and quality of life (QOL) data, remains to be elucidated. Conclusions: Burosumab has shown significant therapeutic effectiveness in treating children with XLH, highlighting its potential as a key treatment option. [ABSTRACT FROM AUTHOR]

The glomerular filtration rate (GFR) is the outcome of glomerular hemodynamics, influenced by a series of parameters: renal plasma flow, resistances of afferent arterioles and efferent arterioles (EAs), hydrostatic pressures in the glomerular capillary and Bowman's capsule, and plasma colloid osmotic pressure in the glomerular capillary. Although mathematical models have been proposed to predict the GFR at both the single-nephron level and the two-kidney system level using these parameters, mathematical equations governing glomerular filtration have not been well-established because of two major problems. First, the twokidney system-level models are simply extended from the equations at the single-nephron level, which is inappropriate in epistemology and methodology. Second, the role of EAs in maintaining the normal GFR is underappreciated. In this article, these two problems are concretely elaborated, which collectively shows the need for a shift in epistemology toward a more holistic and evolving way of thinking, as reflected in the concept of the complex adaptive system (CAS). Then, we illustrate eight fundamental mathematical equations and four hypotheses governing glomerular hemodynamics at both the single-nephron and two-kidney levels as the theoretical foundation of glomerular hemodynamics. This illustration takes two steps. The first step is to modify the existing equations in the literature and establish a new equation within the conventional paradigm of epistemology. The second step is to formulate four hypotheses through logical reasoning from the perspective of the CAS (beyond the conventional paradigm). Finally, we apply the new equation and hypotheses to comprehensively analyze glomerular hemodynamics under different conditions and predict the GFR. By doing so, some concrete issues are eliminated. Unresolved issues are discussed from the perspective of the CAS and a desinger's view. In summary, this article advances the theoretical study of glomerular dynamics by 1) clarifying the necessity of shifting to the CAS paradigm; 2) adding new knowledge/insights into the significant role of EAs in maintaining the normal GFR; 3) bridging the significant gap between research findings and physiology education; and 4) establishing a new and advanced foundation for physiology education. [ABSTRACT FROM AUTHOR]

Introduction: We aim to explore the association between NSAIDs consumption, Symptomatic Slow Action Drugs for Osteoarthritis (SYSADOA), analgesics, and antiplatelet drugs, and decline in renal function by estimated Glomerular Filtration Rate (eGFR). Methods: We performed a case-control study using the SIDIAP database in Catalonia. We considered defined cases, patients with an eGFR value ≤ 45 ml/min/1.73 m2 in the period 2010–2015 with a previous eGFR value ≥ 60, and no eGFR ≥ 60 after this period. Controls had an eGFR ≥ 60 with no previous eGFR < 60. Five controls were selected for each case, matched by sex, age, index date, Diabetes Mellitus and Hypertension. We estimated Odds Ratios (OR, 95% Confidence Intervals) of decline in renal function for drugs group adjusting with logistic regression models, by consumption measured in DDD. There were n = 18,905 cases and n = 94,456 controls. The mean age was 77 years, 59% were women. The multivariate adjusted model showed a low risk for eGFR decline for NSAIDs (0.92;0.88–0.97), SYSADOA (0.87;0.83–0.91) and acetaminophen (0.84;0.79–0.89), and an high risk for metamizole (1.07;1.03–1.12), and antiplatelet drugs (1.07;1.03–1.11). The low risk in NSAIDs was limited to propionic acid derivatives (0.92;0.88–0.96), whereas an high risk was observed for high doses in both acetic acid derivatives (1.09;1.03–1.15) and Coxibs (1.19;1.08–1.30). Medium and high use of major opioids shows a high risk (1.15;1.03–1.29). Triflusal showed high risk at medium (1.23;1.02–1.48) and high use (1.68;1.40–2.01). Conclusion: We observed a decline in renal function associated with metamizole and antiplatelet agent, especially triflusal, and with high use of acetic acid derivates, Coxibs, and major opioids. Further studies are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: To assess the rate at which sutureless partial nephrectomy (SLPN) transitions to standard partial nephrectomy (SPN), focusing on preoperative factors that might prompt such conversions. Patients and methods: In this retrospective study, we analyzed the efficacy of SLPN performed on adults at our institution from 2016 to 2023. The subjects were patients diagnosed with localized solid renal tumors. The primary technique employed was resection with scissors and argon beam coagulation for hemostasis, with suturing techniques used only when necessary. Predictive factors necessitating conversion to SPN were identified, and the associations among multiple variables were explored using various statistical analysis methods, including logistic regression, to identify key preoperative predictive factors. Results: Our institution performed 353 SLPN, with 21 cases (5.9%) necessitating conversion to SPN. The conversion rates for the Laparoscopic Partial Nephrectomy (LPN) subgroup and the Robotic-assist Partial Nephrectomy (RPN) subgroup were 7.9% (17/215) and 2.9% (4/138), respectively, nearing statistical significance (P =.066). Significant differences were observed between the conversion group and the no conversion group in terms of preoperative estimated Glomerular Filtration Rate (eGFR), age at surgery, tumor size, and exophytic/endophytic characteristics. Multivariate analysis identified age at surgery, preoperative eGFR, radiological tumor size, and tumor exophytic/endophytic nature as significant predictors for conversion to SPN. Conclusion: This investigation highlights the efficacy and feasibility of SLPN while identifying critical factors influencing the necessity for conversion to SPN. The identified predictors, including younger surgical age, superior preoperative eGFR, and specific tumor characteristics, provide valuable insights for refining surgical strategies. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA).This study was a multi‐institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer‐specific survival (CSS), overall survival (OS), treatment‐related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan–Meier method was used to estimate freedom from local and distant failure, CSS and OS.Seventeen patients with 18 biopsy‐confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6–68.7) years, a median (IQR) tumour size of 3.5 (1.9–4.1) cm and follow‐up (reverse Kaplan–Meier method) of 3.36 (95% confidence interval [CI] 1.6–4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5–5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression‐free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%–100%), 92.3% (95% CI 78.9%–100%) and 82.1% (95% CI 62.1%–100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40–71) mL/min, and at last follow‐up, it was 48 (33–57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end‐stage renal disease.The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA. [ABSTRACT FROM AUTHOR]

The anatomical features spanning from the aortic arch to the proximal carotid artery and the associated cardiovascular risks might significantly influence the development of right carotid plaque. Our research aimed to compare these anatomical and risk factors between individuals with no carotid plaque and those with moderate right-side carotid plaque within a Korean cohort. We conducted a retrospective, cross-sectional analysis involving 413 participants, categorized into a normal group (n = 339) and a right moderate carotid plaque group (defined as > 50% stenosis based on NASCET criteria) (n = 74). We collected data on cardiovascular risk factors and conducted laboratory tests. A 3D model of the carotid artery was constructed using cranio-cervical computed tomography angiography (CTA) data through semi-automated software. Measurements taken on this 3D model included the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and carotid artery bifurcation (CAB) in terms of maximal vascular diameter, sectional area, angles of carotid bifurcation and ICA, and carotid tortuosity. When compared with the normal group, individuals in the right moderate carotid plaque group exhibited smaller angles at the carotid bifurcation, larger CCA diameter and sectional area (p < 0.01), advanced age, and a higher incidence of hypertension, diabetes, and stroke history (p < 0.05), along with reduced glomerular filtration rate (GFR) (p < 0.001). Multivariate analysis revealed that the sectional area of the bifurcation, calcification of the aortic bulb, and GFR were independently associated with the presence of right moderate carotid plaque (p < 0.01). Statistical analyses disclosed significant differences in both clinical risk factors and geometric changes in the region extending from the aortic arch to the proximal carotid artery among subjects with right moderate carotid plaque when compared to those without. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The relationship between α‐Klotho (αK) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum αK protein levels with all‐cause and cause‐specific mortality in a cohort representative of the US population.We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016. A nonlinear association between mortality and αK levels as a quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio.Of the 13 749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29.7 (6.7) kg/m2, and αK was 0.85 (0.31) ng/mL. In the adjusted Cox proportional hazards model with quadratic αK, we found a U‐shaped relationship between all‐cause mortality and αK levels (continuous αK hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.37, 0.85; P = .007; squared‐αK HR = 1.25, 95% CI: 1.11, 1.41; P < 0.001). A similar U‐shaped relationship was noted between αK and cancer mortality in the adjusted Cox proportional hazards model (continuous αK HR = 0.45, 95% CI: 0.19, 1.06; P = 0.07; squared αK HR = 1.32, 95% CI: 1.07, 1.61; P = 0.009). No relationship was present with cardiovascular or other‐cause mortality.In this large diverse cohort, we report a U‐shaped relationship between αK with all‐cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed. [ABSTRACT FROM AUTHOR]

Background and Purpose Approach Background and Key Results Conclusions and Impact Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging.We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR).An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR.These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the capability and imaging criteria of T1 mapping and arterial spin labeling (ASL) MRI to identify renal injury in patients with liver cirrhosis. Methods: We recruited 27 patients with cirrhosis and normal renal function (cirrhosis-NR), 10 with cirrhosis and renal dysfunction (cirrhosis-RD) and 23 normal controls (NCs). All participants were examined via renal T1 mapping and ASL imaging. Renal blood flow (RBF) derived from ASL was measured from the renal cortex, and T1 values weremeasured fromthe renal parenchyma (cortex and medulla). MRI parameters were compared between groups. Diagnostic performances for detecting renal impairment were statistically analyzed. Results: Cortical T1 (cT1) and medullary T1 (mT1) were significantly lower in the NCs than in the cirrhosis-NR group. The cortical RBF showed no significant changes between the NCs and cirrhosis-NR group but was markedly decreased in the cirrhosis-RD group. The areas under the curve (AUCs) for discriminating cirrhosis-NR from NCs were 0.883 and 0.826 by cT1 and mT1, respectively. Cortical RBF identified cirrhosis-RD with AUC of 0.978, and correlated with serum creatinine (r = -0.334) and the estimated glomerular filtration rate (r = 0.483). A classification and regression tree based on cortical RBF and cT1 achieved 85% accuracy in detecting renal impairment in the cirrhosis. Conclusion: Renal T1 values might be sensitive predictors of early renal impairment in patients with cirrhosis-NR. RBF enabled quantifying renal perfusion impairment in patients with cirrhosis-RD. The diagnostic algorithm based on cortical RBF and T1 values allowed detecting renal injury during cirrhosis. [ABSTRACT FROM AUTHOR]