Serum Creatinine Research Articles

P-529. Comparison of Renal Outcomes by Tenofovir Alafenamide Fumarate (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) Containing Regimens for Prevention, and Treatment of HIV and/or HBV Treatment: A Systematic Literature Review and Meta-Analysis

Abstract Background Tenofovir is one of the most widely used agents for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) treatment, and pre-exposure prophylaxis (PrEP). Two forms of tenofovir are currently available: tenofovir disoproxil fumarate (TDF) and its prodrug, tenofovir alafenamide (TAF). TAF is associated with improved renal safety and non-inferior efficacy when compared to TDF. We aimed to comprehensively synthesize the evidence on renal outcomes of TDF and TAF regimens for treatment of HIV-1, HBV, or PrEP. Methods A systematic search of randomized controlled trials (RCTs) that compared TDF vs. TAF for the treatment of HIV-1, HBV, or PrEP and reported changes in estimated glomerular filtration rate (eGFR) or serum creatinine (SCr) from treatment initiation was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Trial Registry. This search was performed on 12/6/2023 and supplemented a previous review by Gupta et al. (2019). Renal outcomes were pooled using mean differences with 95% confidence intervals (CIs). The heterogeneity was assessed using I2 test and explored via subgroup analyses of disease state and duration of follow-up. Results Out of 9,014 studies screened, 24 RCTs (total 21962 participants; 12756 in TAF; 9206 in TDF) reported eGFR outcomes and 21 RCTs (total 18454 participants; 10293 in TAF; 8161 in TDF) reported SCr outcomes. Compared to TDF, the use of TAF was associated with an improvement of 3.69 mL/min/1.73m2 (95% CI: 1.89 – 5.49) in eGFR from treatment initiation (I2 = 95.83%) (Figure 1). Subgroup analyses of disease state and study duration for eGFR are described in Table 1. The effect sizes were consistent across subgroups, low levels of heterogeneity were observed for analyses lasting > 48 weeks and for HBV. TAF was also associated with an improvement of SCr of 0.03 mg/dL (95% CI: 0.02 to 0.04) from treatment initiation compared to TDF (I2 = 82.47%) (Figure 2). Conclusion This synthesis of RCT results supports a comparative renal safety advantage of TAF over TDF when evaluated across a broad and diverse range of people including those diagnosed with HIV-1, HBV, HIV and HBV coinfection, and those receiving PrEP. Further exploration of sources of heterogeneity and the evaluation of observational study data are needed. Disclosures Kyu Yun Park, PharmD, Gilead Sciences, Inc.: Grant/Research Support Connor Willis, PharmD, ARUENA: Grant/Research Support|AstraZeneca: Grant/Research Support|Bayer: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|DexCom: Grant/Research Support|Gilead: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Grail, Inc.: Grant/Research Support|Jazz: Grant/Research Support|Mainstay Medical: Grant/Research Support|Novartis: Grant/Research Support|PEAR Therapeutics: Grant/Research Support Rachel Rogers, Gilead Sciences, Inc.: Employee; Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Amy Weinberg, DNP, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Julia Green, MS, APRN, AGNP-C, ACRN, AAHIVE, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Aileen Chi, PharmD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Nathorn Chaiyakunapruk, PhD, Gilead Sciences, Inc.: Grant/Research Support

P-809. Evaluating the Usage, Safety, and Accuracy of Vancomycin Dosing Practices at VA Eastern Colorado Health Care System (VA ECHCS)

Abstract Background Vancomycin is a glycopeptide antibiotic used as a mainstay of therapy for gram positive bacterial infections, including MRSA (methicillin-resistant staphylococcus aureus). Vancomycin requires pharmacokinetic calculations to determine dosing and close therapeutic drug monitoring to achieve goal trough between 15-20 mg/L (AUC/MIC goal between 400-600 mg ■h/L) and prevent nephrotoxicity. The purpose of this study is to assess our current vancomycin usage patterns, including empiric dosing accuracy & safety outcomes to help inform a decision whether a change to our current practice is indicated. Methods This retrospective, observational cohort study evaluated 117 vancomycin trough levels from 63 patients who received at least two doses of vancomycin between August 1, 2022 and July 31, 2023. Patients were excluded if they received hemodialysis or were dosed by random levels in the setting of severe renal dysfunction. Collected demographics included age, sex, weight, height, BMI, indication for vancomycin, dosing, trough levels, source of infection, MRSA nares, concomitant nephrotoxic medications, spinal cord injury diagnosis, serum creatinine, and cystatin C. Estimated AUC was calculated using VancoPK.com based on the reported trough using patient specific pharmacokinetic parameters. This study is exempt from IRB approval. Results A total of 58 trough levels from 49 patients were included. The majority of patients were male (87.7%) with an average age 61±13 years old. Out of the 58 trough levels evaluated, 20 (41%) were at goal. Of the levels not a goal 27 (71%) were subtherapeutic, and 11 (29%) were supratherapeutic. The estimated AUC was at goal for 35 (60%) of the 58 total troughs. Of the 27 patients who had a subtherapeutic trough 21 (77%) had an AUC at goal, and 14 of them increased the dose despite having a therapeutic AUC. Only 1 patient (2%) developed possible vancomycin associated AKI (acute kidney injury). Conclusion A higher number of patients were within therapeutic range when evaluating AUC compared to trough. The low incidence of vancomycin associated AKI was likely due to low frequency of supratherapeutic troughs in this study. Further analysis of these results will be used to identify opportunities for education and improvement of our current vancomycin dosing process. Disclosures All Authors: No reported disclosures

Ambient PM25 Plus High‐Fat Diet Exacerbated Kidney Injury in Mice by Activating Ferroptosis Mediated TGF‐β1/Smad2 Signaling Pathway

ABSTRACTThe prevalence of chronic kidney disease (CKD) is on the rise globally, posing a significant public health concern. Numerous studies have indicated that the consumption of a high‐fat diet (HFD) can lead to renal injury, a condition closely linked to CKD. Additionally, research has shown that exposure to ambient PM2.5 is associated with an increased risk of CKD, suggesting that PM2.5 may serve as an environmental risk factor for CKD. However, the synergistic impact of PM2.5 and HFD on renal injury remains poorly understood. Therefore, the objective of our study was to investigate the combined effect of PM2.5 and HFD on renal injury. Male C57BL/6J mice were subjected to a 12‐week feeding regimen of either a normal diet or a HFD, while also being exposed to either saline or ambient PM2.5 through intratracheal instillation twice a week. Evaluation of renal function demonstrated that the HFD significantly elevated levels of serum blood urea nitrogen and serum creatinine. Furthermore, the combination of PM2.5 and HFD exhibited a synergistic effect, exacerbating the aforementioned indicators of kidney injury. Masson's trichrome staining revealed that both the HFD and/or PM2.5 induced renal fibrosis, with PM2.5 exacerbating the HFD‐induced renal fibrosis in the mice. In this study, Western blot analysis was conducted to examine the protein expressions of TGF‐β1 and p‐Smad2 in kidney tissues, which were found to be significantly increased in response to a HFD and/or exposure to PM2.5. Additionally, the impact of PM2.5 combined with HFD on renal ferroptosis was investigated. The results revealed that both HFD and PM2.5 led to an elevation in 4‐HNE concentration, a reduction in GSH content, a decrease in GPX4 protein expression, and an increase in ACSL4 protein expression in kidney tissues. Moreover, the combined exposure to PM2.5 and HFD exhibited a synergistic effect on GPX4 alterations in the kidney. Collectively, our findings suggest that the presence of PM2.5 exacerbates the renal injury, oxidative stress, and renal fibrosis induced by a HFD. This detrimental effect may be attributed to the activation of the ferroptosis‐mediated TGF‐β1/Smad2 signaling pathway.

P-1488. Clinical Efficacy of Minocycline in the Treatment of Carbapenem-resistant Acinetobacter baumannii Pneumonia

Abstract Background Minocycline is one of the few antibiotics that remain active against carbapenem-resistant Acinetobacter baumannii (CRAB). However, the efficacy of minocycline in CRAB pneumonia has not been clearly demonstrated. Methods We conducted a multicenter retrospective cohort study at three university-affiliated teaching hospitals in patients with CRAB pneumonia who were admitted between October 2017 and October 2022. Patients were divided into two groups depending on whether minocycline was included in the antibiotics treatment regimen. Propensity scores for minocycline use were calculated using logistic regression, and logistic regression with overlap weighting was conducted to assess whether there were significant differences in outcome variables and safety variables between the two groups. Results We enrolled 430 CRAB pneumonia patients, among which 201 patients were treated with minocycline and 229 patients without minocycline. Intensive care unit stay was more frequent (77.6% vs 65.1%, P value = 0.006) and serum creatinine was higher (0.9 vs 0.8 mg/dL, P = 0.023) in the minocycline group than in the non-minocycline group. Variables associated with minocycline use in logistic regression were cerebrovascular disease (odds ratio [OR] 4.51, 95% confidence interval [CI] 2.07–9.85, P < 0.001), higher serum creatinine (OR 1.37, 95% CI 1.01–1.87, P = 0.046), and combination antibiotic regimen (OR 124.73, 95% CI 43.23–359.84, P < 0.001). Bacteremia (OR 0.19, 95% CI 0.05–0.73, P = 0.016) and lower Charlson comorbidity index (CCI) (OR 0.76, 95% CI 0.64–0.91, P = 0.003) were inversely associated with minocycline use. The clinical success rate on day 14 was higher in the minocycline-treated group (58.3% vs 41.7%, P < 0.001). In the adjusted model, the use of minocycline was significantly associated with clinical success (adjusted OR [aOR] 3.88, 95% CI 1.55–9.70, P = 0.004), lower 28-day mortality (aOR 0.28, 95% CI 0.10–0.79, P = 0.016), and a longer mechanical ventilator-free day (4.51 days longer, 95% CI 2.64–6.37, P < 0.001). Conclusion Minocycline, when used as a combination treatment in the treatment of CRAB pneumonia, showed superior results in terms of 14-day clinical success and 28-day mortality. Minocycline may be considered one of the antibiotic treatment options for CRAB pneumonia. Disclosures Kyungmin Huh, M.D., Ph.D., bioMérieux: Grant/Research Support|GSK Korea: Advisor/Consultant|Pfizer Korea: Honoraria|Takeda Korea: Advisor/Consultant

SONOGRAPHIC MARKERS IN THE EARLY DETECTION OF RENAL DYSFUNCTION IN DIABETIC ADULTS

Objective: This study aimed to use the sonographic markers in the early detection of renal dysfunction in diabetic adults. Study design: The study design was cross sectional in nature. Place and duration of study: The study was conducted at Allied Hospital Faisalabad. Duration of study was 4 months from November 2024 to February 2025. Material and methods: The current study comprised a sample of 250 persons. All diabetic adults (aged18-90) all BMI categories and both genders were consenting before participation, experienced ultrasonography collected their demographic, anthropometric data and blood samples collection. The data was presented as mean and standard deviation (mean ±SD). One-way analysis of variance (ANOVA) was used to calculate the statistical analysis, and the Pearson correlation coefficient was computed for bivariate associations. The statistical significance was established at the 5% (p<0.05) level using the SPSS version 27. Results: The results showed that male participants had higher serum creatinine and eGFR levels with increasing BMI. Serum creatinine ranged from 0.876±0.341 mg/dL in males with BMI <18.5 kg/m² to 1.325±0.677 mg/dL in those with BMI >30 kg/m², with an overall mean of 0.997±0.503 mg/dL (p=0.113). eGFR increased from 77.257±11.959 mL/min/1.73 m² to 101.125±16.762 mL/min/1.73 m², with a significant p-value of 0.001. In females, serum creatinine ranged from 0.790±0.310 mg/dL in the <18.5 BMI group to 1.097±1.004 mg/dL in the >30 BMI group, with a mean of 0.963±0.798 mg/dL (p=0.014). eGFR ranged from 62.200±10.464 mL/min/1.73 m² to 84.595±13.180 mL/min/1.73 m², with a significant p-value of <0.001. Conclusions: Sonographic variables have demonstrated great promise in the early identification of renal impairment in persons with diabetes. Before symptoms manifest or laboratory data change dramatically, early alterations in kidney size, cortical echogenicity, and resistive indices can be identified using imaging techniques such Doppler ultrasonography and greyscale ultrasound.

Effect of adenosine triphosphate on methylphenidate-induced oxidative and inflammatory kidney damage in rats

The purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied via oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use.

Cardiometabolic index as a predictor of gallstone incidence in U.S. adults: insights from NHANES 2017–2020

BackgroundGallstone disease (GSD) is associated with obesity. The Cardiometabolic Index (CMI), a metric that accurately assesses central adiposity and visceral fat, has not been extensively studied in relation to GSD risk. This study investigates the link between CMI and GSD incidence in U.S. adults.MethodsThis study utilized data from the National Health and Nutrition Examination Survey(NHANES)(2017–2020) to assess the association between CMI and GSD, adjusting for confounders such as age, sex, race, chronic diseases, and lifestyle factors. Multivariable logistic regression models and subgroup analyses were employed. Generalized Additive Models (GAM) and advanced curve fitting techniques were used to explore potential non-linear relationships, with threshold effects determined via piecewise linear regression if such relationships were identified. Receiver Operating Characteristic (ROC) curves evaluated and compared the predictive performance of CMI, Body Mass Index (BMI), and Waist Circumference (WC), establishing optimal cutoff values along with their sensitivity and specificity.ResultsThis study included 3,706 participants, of whom 10.6% (392) had GSD. Participants with GSD showed significantly higher CMI values (0.57 vs. 0.44, P = 0.0002). The GSD group included more females and older adults, with increased risks for hypertension, diabetes, higher serum cholesterol and creatinine levels, and a higher risk of cancer. Logistic regression analysis revealed that higher CMI was significantly associated with greater GSD incidence (OR = 1.19, 95% CI = 1.02–1.38, P < 0.0001). The ROC curve demonstrated superior predictive performance (AUC = 0.778), outperforming conventional metrics like BMI and WC. GAM analysis indicated a non-linear positive correlation between CMI and GSD, with an optimal threshold of 0.996. Subgroup analysis found the strongest association among females, individuals aged 20–39, non-Hispanic Whites, those without a history of coronary heart disease, and alcohol consumers.ConclusionOur study reveals a nonlinear positive correlation between the CMI and the incidence of GSD among U.S. adults, with a threshold value of 0.996. Despite limitations in sample size that constrained the analysis of a fully adjusted model, after adjusting for confounding factors, the AUC for predicting GSD using CMI reached 0.778, surpassing traditional metrics. These findings underscore the importance of CMI as a critical risk factor and emphasize the necessity of targeted interventions for high-risk populations.

Lack of effect of renal function on uptake of 99mTc-sestamibi in renal masses.

The appropriate clinical management of indeterminate small renal masses can be improved based on accurate risk stratification. This study aimed to investigate the impact of renal function on the uptake of technetium-99m (99mTc)-sestamibi, a widely available imaging agent that can be utilized to identify oncocytomas and other benign/indolent renal masses. A retrospective cohort study was conducted, involving 100 consecutive patients who underwent 99mTc-sestamibi single-photon emission computed tomography/computed tomography. Renal function was evaluated based on creatinine levels and glomerular filtration rate (GFR). Statistical analyses, including correlation and regression analyses, were performed to explore the relationship between renal function and 99mTc-sestamibi uptake. The results revealed that discrepancies can occur between imaging and pathology results, emphasizing the need for careful interpretation of imaging findings. Correlation analysis demonstrated no significant correlation between relative tumor uptake of 99mTc-sestamibi and GFR or serum creatinine levels. These findings highlight the relative independence of renal function and 99mTc-sestamibi uptake and suggest sestamibi may be of use even in patients with relatively poor renal function. However, further research with larger sample sizes is required to validate and generalize these findings. Ultimately, understanding the broad variety of applicability of 99mTc-sestamibi uptake for risk stratification of renal malignancy could aid in appropriate clinical decision-making.

P-1789. Implementation of Pathogen Independent Model Informed Precision AUC-based Dosing of Vancomycin at University Hospital Wuerzburg (UKW)

Abstract Background The IDSA guideline concerning monitoring vancomycin in MRSA infections, published in March 2020, recommends model informed precision AUC based dosing for vancomycin. The application of pharmacometrics software with Bayesian calculating is recommended. The summary of product characteristics of vancomycin, issued by EMA (European Medicines Agency), includes also details regarding model informed precision dosing for vancomycin therapies, irrespective of targeted or identified pathogens. Due to the low prevalence of MRSA infections at UKW, model informed precision AUC-based dosing has been instituted for all parenteral vancomycin therapies. Methods The target for vancomycin AUC/MIC (minimum inhibitory concentration) is a range of 400 – 600 mg*h/L over 24 hours. Individual patient covariates, personal dosing information and vancomycin concentrations were converted into dosing recommendations with InsightRX. In order to record the effect of the intervention, the target attainment and the occurrence of AKI (acute kidney injury, defined as an increase in serum creatinine of ≥ 0.3 mg/dL within 48 h) is recorded 18 months before and 12 months after the implementation of the new dosing strategy. Results Since October 2022, a workflow for model informed AUC-based dosing has been launched across 12 wards - mainly intensive care units - encompassing 215 beds. In the conventional dosing strategy according to trough dosing, AKI occurred in 60 of 216 therapies, while AKI was detected in 8 out of 57 AUC-guided vancomycin therapies resulting in an odds ratio of 2.32 [CI 95 % 1.08 – 5.59]. Significantly more AUC guided therapies were in the therapeutic range of 400 – 600 mg*h/L after 120 hours than trough-based vancomycin therapies reached the target [55.1 % vs 70.2 %, OR 0.52, CI 95 % 0.27 – 0.97]. Additionally, more trough-based therapies were in a supratherapeutic range than AUC guided therapies [24.5 % vs 8.8 %, OR 3.23, CI 95 % 1.35 – 9.98] Conclusion The unique concept of pathogen independent model-informed AUC-based dosing of vancomycin was successfully integrated into the clinical routine work. Early dose individualization due to AUC-based dosing can contribute to increase drug therapy safety and improved patient safety for vancomycin therapies. Disclosures All Authors: No reported disclosures

Right ventricular function and pulmonary coupling in relation to loop diuretic resistance in patients with congestive heart failure

Abstract Background Right ventricular (RV) dysfunction has been proven to be a prognostic factor among heart failure (HF) patients. Loop diuretic resistance (LDR) is associated with worse clinical outcomes, greater symptom burden and mortality. Limited data exist to characterise the relation between RV and kidney function, especially LDR. Purpose To assess relationship of different echocardiographic RV function parameters with loop diuretic resistance in patients with congestive HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Transthoracic echo with detailed assessment of right heart geometry and function, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. A TAPSE/PASP ratio was used to assess RV to pulmonary circulation coupling. Results are presented as mean±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, mean left ventricle ejection fraction (EF) 37.3±13.0 %, mean E/e’ 18.6±5.0, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: pulmonary artery systolic pressure (PASP), right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), serum creatinine concentration, serum urea concentration, serum low-density cholesterol (LDL) concentration (results are shown in the table). TAPSE/PASP on admission correlated negatively with NT-pro BNP (r -0.44 , p=0.007) and positively with diuresis/40mg of furosemide (r 0.38, p=0.02). In the multivariable model, the significant negative relationship between LDR and TAPSE/PASP (beta coefficient -0.653, p= 0.047) as well as LDL (beta coefficient -0.055, p=0.043) was observed. Conclusions TAPSE/PASP, one of the most significant non-invasive indexes of RV failure, assessed at admission might be a clinically relevant marker of LDR in patients with congestive HF exacerbation. Study group characteristics

P-1260. Validation of Modified First-Order Kinetic Equation for Vancomycin Area Under the Curve Calculation in Neonatal Patients

Abstract Background Current guideline emphasizes a ratio of 24 hour-area under the curve (AUC) to minimum inhibitory concentration (MIC) of ≥ 400 mg.h/L as the primary pharmacokinetic and pharmacodynamics predictor of vancomycin activity against serious methicillin-resistant S. aureus (MRSA) infections. Premature infants admitted to neonatal intensive care unit (NICU) are at high risk of Staphylococcal infections due to immunocompromised state and frequent procedures; however, the availability of vancomycin AUC calculator for this population is limited. Methods Neonates received vancomycin for at least 4 days between January 2018 and December 2023 with steady-state trough level were included. The modified first-order kinetic equation using population-based distributive volume (Vdf) of 0.7 L/kg and trough level were compared to the Vanc App program validated in infants aged 0 to 90 days with post-menstrual age (PMA) ≥ 25 weeks and weight ≥ 500 grams. Ratio and percentage difference of calculated AUCs between the two models were assessed, as were safety parameters, including urine output &amp;lt; 0.5 mL/kg/hr over at least 6 hours, serum creatinine increases by 0.3 mg/dL or 1.5 times baseline, duration of culture positivity, and recurrence of same infection within 14 days. Results We identified 95 neonates with 56% male. The median (range) PMA was 30.1 (24.2 - 44.3) weeks, age was 21 (1 - 137) days, and weight was 1.2 (0.54 - 4.30) kg. Five cases had culture-proven MRSA infections. The average vancomycin dose was 37 mg/kg/day with median (range) duration of 7 (4 - 45) days. Acute kidney injury was identified in 2.1% of patients. Target AUC was achieved in 78% of cases. The average duration of culture positivity was 2.2 days, and no patients exhibited recurrent infections within 14 days after stopping vancomycin. The median (IQR) accuracy was 0.98 (0.95 - 1.01), and bias was -0.02 (-0.05 - 0.01). To obtain concordant AUC results, the mean (SD) Vdf was 0.67 (0.09) L/kg. No statistically significant differences between the two models in identifying AUC outside of therapeutic range (p=0.083). Conclusion The modified first-order kinetic equations can achieve comparable AUC estimates in neonates by incorporating a population PK-based VDf of 0.7 and single trough level, eliminating the need for additional blood draws. Disclosures All Authors: No reported disclosures

The Significance of Renal Impairment in Children with Eating Disorders

Background: Eating disorders have previously been associated with renal impairment. Low muscle mass reduces serum creatinine used for the calculation of the estimated glomerular filtration rate (eGFR), leading to overestimation of renal function. To solve this problem, the development of a tool to detect renal impairment in individual patients with a specific muscle mass is required to individualize risk assessment for further management. The objectives of our study were as follows: To investigate the percentage drop in creatinine (pdCr) during rehydration as a new indicator of renal dysfunction not dependent on muscle mass and to investigate a correlation between cardiovascular function and fluid management with renal function. Methods: In a 5-year retrospective cohort study of all consecutive children admitted because of an eating disorder, renal function expressed as eGFR on admission and as pdCr between admission and the lowest creatinine level was analysed in relation to cardiovascular parameters and fluid management. Results: We included 29 patients. The mean age was 13.4 years. A pdCr after admission was noted in 26/29 (89.7%). The eGFR was &lt;90 in 15 (65%) and improved to &gt;90 in 13/15 (86.6%). In patients with a fluid management plan, there was a median of 18.6% for those with pdCr and 6.4% (p = 0.02) for those without. Renal dysfunction was not related to cardiovascular parameters. Conclusions: The majority of patients with an eating disorder had renal impairment. PdCr was more sensitive in the detection of renal impairment in individual patients compared to eGFR.

Relationships between multivitamins, blood biochemistry markers, and BMC and BMD based on RF: A cross-sectional and population-based study of NHANES, 2017-2018.

Previous studies have separately suggested a possible association between the vitamin exposure, blood biochemical indicators, and bone density. Our study aimed to investigate the relationship between vitamin exposure serum concentrations, blood biochemical indicator serum concentrations, and BMC and BMD using the NHANES 2017-2018 nutrient survey data. This population-based cross-sectional study aimed to explore these associations. In this study, we measured vitamin serum concentrations, serum ion serum concentrations, and serum biochemical indicators in adults participating in the NHANES. Skeletal status was assessed by evaluating BMC and BMD in the whole body. Given the inclusion of multiple variables and diverse data types, we used the RF to fit a multivariable model to estimate the associations between vitamin serum concentrations, blood biochemical indicator serum concentrations, and skeletal status. Under the dimension reduction and comparison selection of RF model, we identified ALP, CPK, and creatinine serum concentrations as the most important factors associated with BMC and BMD in multiple skeletal sites, and the gender, age, height, weight, and body mass index which were found to be related to BMC and BMD in different skeletal sites. Vitamin D and blood calcium serum concentrations were not the important factors associated with BMC and BMD and the three blood biochemical indexes were more important than the vitamin level for BMC and BMD. The effect of vitamin serum concentrations and blood calcium serum concentrations on human bone density was not significant. ALP, CPK and creatinine serum concentrations body development indicators were identified as the most important factors related to bone status. The RF model can be used to comprehensively evaluate the effects of vitamin content and blood biochemistry serum concentrations in adults on BMC and BMD.

Bias-corrected serum creatinine from UK Biobank electronic medical records generates an important data resource for kidney function trajectories

Loss of kidney function is a substantial personal and public health burden. Kidney function is typically assessed as estimated glomerular filtration rate (eGFR) based on serum creatinine. UK Biobank provides serum creatinine measurements from study center assessments (SC, n = 425,147 baseline, n = 15,314 with follow-up) and emerging electronic Medical Records (eMR, “GP-clinical”) present a promising resource to augment this data longitudinally. However, it is unclear whether eMR-based and SC-based creatinine values can be used jointly for research on eGFR decline. When comparing eMR-based with SC-based creatinine by calendar year (n = 70,231), we found a year-specific multiplicative bias for eMR-based creatinine that decreased over time (factor 0.84 for 2007, 0.97 for 2013). Deriving eGFR based on SC- and bias-corrected eMR-creatinine yielded 454,907 individuals with ≥ 1eGFR assessment (2,102,174 assessments). This included 206,063 individuals with ≥ 2 assessments over up to 60.2 years (median 6.00 assessments, median time = 8.7 years), where we also obtained eMR-based information on kidney disease or renal replacement therapy. We found an annual eGFR decline of 0.11 (95%-CI = 0.10–0.12) versus 1.04 mL/min/1.73m2/year (95%-CI = 1.03–1.05) without and with bias-correction, the latter being in line with literature. In summary, our bias-corrected eMR-based creatinine values enabled a 4-fold increased number of eGFR assessments in UK Biobank suitable for kidney function research.

Follow-up biopsies with microvascular inflammation and persistent donor specific antibodies identify ongoing rejection in pediatric kidney transplant recipients.

Inadequate treatment of acute rejection (AR) in pediatric kidney transplant recipients (KTR) can contribute to early allograft failure. Serum creatinine is an insensitive marker of allograft function, especially in the pediatric population, and may not detect ongoing rejection after treatment. We evaluated the utility of follow-up biopsies to detect persistent inflammation and future episodes of rejection. We performed a single-center retrospective review to identify pediatric KTR with biopsy-proven rejection and a subsequent follow-up biopsy, noting type of AR, Banff scores, serum creatinine, and presence of donor specific antibodies (DSA). Outcomes included resolution of AR, change in eGFR, DSA, persistent microvascular inflammation (MVI) and future episodes of AR. Twelve cases of cellular (TCMR), 9 antibody-mediated (AMR), and 8 mixed cases of AR were identified among 23 KTR. Resolution was noted in 75% with TCMR, significantly higher than AMR (22%) or mixed rejection (13%), p < 0.01. Those without resolution of AR on follow-up biopsy were more likely to have ongoing episodes of AR or graft loss (p = 0.02). Persistence of DSA and MVI was associated with lack of AR resolution (p = 0.01 and p = 0.001, respectively). Those with persistent MVI on follow-up biopsy had higher probability of future AR events or graft loss, p = 0.003. Follow-up biopsies to assess response to AR treatment revealed that most cases of TCMR were successfully treated but that AMR and mixed rejection portend a componentof chronicity and more complicated course. Identification of persistent subclinical inflammation predicts future rejection episodes, has adverse effects on graft longevity, and can inform the need for additional treatment. We advocate for implementation of a follow-up biopsy protocol and future study of non-invasive biomarkers paired with protocol biopsies.

Simulated microgravity predisposes kidney to injury through promoting intrarenal artery remodeling.

Spaceflight-induced multi-organ dysfunction affects the health of astronauts and the safety of in-orbit flight. However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia-reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition. Relative to controls, 31-day hindlimb unweighting had no obvious effect on serum creatinine and urea nitrogen levels as well as on renal injury scores; however, animals in the HU group showed an impaired renal recovery to ischemia-reperfusion injury. Ultrasonography showed that renal resistive index was increased, which indicated an altered renal hemodynamics induced by simulated microgravity. The enhanced vasoconstriction mediated by the Rho-kinase pathway and impaired vasodilation mediated by NO-eNOS of the intrarenal artery contributed to the altered renal hemodynamics. Simulated microgravity predisposes the kidney to ischemia-reperfusion injury. The altered renal hemodynamics induced by renal arterial remodeling may account for the increased renal injury susceptibility, providing a target for early intervention in kidney dysfunction under microgravity.

Preoperative predictive indicators for resolution of hypertension in patients with unilateral primary aldosteronism: development of a nomogram model

BackgroundPrimary aldosteronism (PA) is the leading surgically treatable cause of hypertension, with adrenalectomy as the definitive treatment for unilateral PA (UPA). However, some patients have persistent hypertension after surgery. This study aims to identify preoperative factors affecting surgical outcomes and develop a predictive model for postoperative hypertension resolution.MethodsWe reviewed and analyzed the medical records of 206 patients who underwent unilateral adrenalectomy for UPA at Qilu Hospital of Shandong University (2011–2022). As a training cohort, the data of the 166 patients from 2013 to 2022 was analyzed using univariate and multivariate logistic regression to explore the relationship between preoperative clinical and biochemical data and postoperative BP normalization. The remaining 40 patients from 2011 to 2012 were used as a validation cohort. A predictive model of the nomogram was constructed utilizing significant variables through multivariate logistic regression analysis. The model’s effectiveness was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves and compared with previous prediction models using the Delong test.ResultsIn the training cohort of 166 patients, 78 (46.9%) achieved postoperative normotension without medication, while 88 (53.1%) required ongoing antihypertensive treatment. Multifactorial analysis identified age, number of antihypertensive medications, preoperative maximum systolic blood pressure (SBP), left ventricular ejection fraction (LVEF), serum creatinine (Cr) levels, and a history of hypokalemia as independent predictors of postoperative BP normalization. Calibration curves showed excellent agreement between predicted and actual outcomes, and DCA indicated that clinical interventions based on this model are beneficial at various risk thresholds. Comparison with previous models showed our model outperformed the Aldosteronoma Resolution Score (ARS) in the Asian population and was comparable to the Morisaki score.ConclusionA predictive model developed with variables including age, number of anti-hypertensive medications, preoperative maximum SBP, LVEF, serum Cr levels, and history of hypokalemia effectively predicts therapeutic outcomes following unilateral adrenalectomy for UPA patients.

Calcium to magnesium ratio as a superior biomarker for nephrolithiasis detection in primary hyperparathyroidism

Primary hyperparathyroidism (pHPT) is marked by mineral imbalances, often leading to nephrolithiasis and osteoporosis. While imaging remains the cornerstone for stone detection, there is growing interest in biochemical markers that could enhance diagnostic accuracy. This study investigates the calcium-to-magnesium (Ca/Mg) ratio as a novel biomarker for nephrolithiasis, comparing its utility to traditional 24-h urinary calcium excretion and exploring its broader clinical implications. In this retrospective study of 367 pHPT patients, clinical, biochemical, and bone mineral density (BMD) data were analyzed. Nephrolithiasis was diagnosed via imaging, and the diagnostic performance of the Ca/Mg ratio and urinary calcium excretion was assessed through receiver operating characteristic analysis. Multivariable regression was employed to identify predictors of kidney stones. The Ca/Mg ratio, with an optimal cutoff of 6.35, demonstrated superior specificity (78%) compared to 24-h urinary calcium excretion (44%) while maintaining comparable sensitivity (71% vs. 78%). Elevated Ca/Mg ratios strongly correlated with nephrolithiasis, independent of other demographic factors. Hypomagnesemia was linked to a higher prevalence of kidney stones, reduced BMD, and increased serum calcium and creatinine levels, emphasizing its impact on skeletal and renal health. The Ca/Mg ratio emerges as a promising, non-invasive biomarker for nephrolithiasis in pHPT, outperforming traditional urinary calcium measures. It reflects underlying mineral imbalances and offers a practical tool for risk stratification and clinical decision-making. These findings underscore the need for further research into magnesium-targeted interventions, which may transform the management of pHPT-related complications.

Factors Determining the Need for Ultrafiltration in Cardiorenal Syndrome

This study investigates the factors determining the need for ultrafiltration (UF) in patients with cardiorenal syndrome presenting with hypervolemia-related symptoms and signs. A total of 88 patients hospitalized for hypervolemia were treated according to current guidelines, with UF employed as a rescue therapy when diuretic treatment failed to achieve adequate decongestion. Data collected included medical history, laboratory findings, blood pressures, diuretic doses, spot urine sodium (measured 6 hours after diuretic therapy), response to diuretics, postdischarge creatinine levels, rehospitalization rates, and mortality rates. UF was required in 23.90% of patients due to insufficient response to diuretics, with a higher rate observed in men (34.10%) compared with women (13.64%). Patients needing UF had lower systolic blood pressure, higher initial serum creatinine levels, and elevated pro-B-type natriuretic peptide levels. Statistical analysis showed that an increase in initial creatinine levels raised the risk of requiring UF by 6.443 times, while a one-unit decrease in urine sodium increased the risk by 1.037 times. These findings suggest that male gender, high pro-B-type natriuretic peptide levels, low spot urine sodium, low systolic blood pressure, and high initial creatinine levels may predict the need for UF. Further research involving larger patient cohorts is necessary to refine these criteria and develop a risk score.

Hypertensive load predicts recovery of renal function for patients undergoing revascularisation for renal artery stenosis

Renal ischaemia due to renal artery stenosis produces two differing responses - a juxtaglomerular hypertensive response and cortical renal dysfunction. The reversibility of renal impairment is not predictable, and thus renal revascularisation is controversial. This study aims to test the hypothesis that the hypertensive response to renal ischaemia reflects viable renal parenchyma, and thus could be used to predict the recovery in renal function. A retrospective analysis was performed of all patients who had renal revascularisation for renal impairment in a defined geographical area (West of Scotland, population 2.4 million) between 2008 and 2024. Clinical records were used to determine the pre-intervention blood pressure, anti-hypertensive medication load and renal function, and post-intervention outcomes. The Hypertensive Index (HTi), a combined measure of systolic blood pressure and antihypertensive drug load, was used as a measure of pre-intervention hypertensive response. 75 patients had intervention for renal impairment over 15 years (68 endovascular, 7 open). Mean pre-intervention serum creatinine of 323 µmol/L was reduced to 191 umol/L at discharge and 182 µmol/L at 6-month follow-up. Refractory hypertension (HTi > 120) was associated with a significant benefit from revascularisation with improved renal function (p = 0.003) and reduced risk of future dialysis (p = 0.001). Renal impairment with no hypertensive response was highly predictive of the need for future dialysis. The hypertensive index is a good predictor of the impact of renal revascularisation on improving renal function with good outcomes in selected patients, and the absence of this is an indicator of chronic non-reversible renal dysfunction.