Search

Background/Objectives : To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration-time curve (AUC) in adult patients with normal renal function. Methods : We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling. The population PK parameters derived were employed in Monte Carlo simulations to evaluate the adequacy of the current dosing regimen and to formulate dosing recommendations. Results : The PK profiles were optimally described by a two-compartment model, with body weight and age as significant covariates affecting total clearance. The simulations indicated that to achieve a therapeutic target-defined as an AUC at steady-state over 24 h of 400-600 mg·h/L-daily doses ranging from 60 to 70 mg/kg are necessary in adults with normal renal function. Conclusions : This study underscores the need to actively adjust dosage and administration based on a vancomycin PK model that adequately reflects the demographic characteristics of patients to meet both safety and efficacy standards.

This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free ( f ) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions ( f T >MIC ). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40% f T >MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100% f T >MIC or a 90%PTA for 100% f T >4MIC , higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Si, Ge, Lv, Li, Chen and Yuan.)

Background: Persistent acute kidney injury (AKI) after cardiac surgery is not uncommon and linked to poor outcomes., Hypothesis: The purpose was to develop a model for predicting postoperative persistent AKI in patients with normal baseline renal function who experienced AKI after cardiac surgery., Methods: Data from 5368 patients with normal renal function at baseline who experienced AKI after cardiopulmonary bypass cardiac surgery in our hospital were retrospectively evaluated. Among them, 3768 patients were randomly assigned to develop the model, while the remaining patients were used to validate the model. The new model was developed using logistic regression with variables selected using least absolute shrinkage and selection operator regression., Results: The incidence of persistent AKI was 50.6% in the development group. Nine variables were selected for the model, including age, hypertension, diabetes, coronary heart disease, cardiopulmonary bypass time, AKI stage at initial diagnosis after cardiac surgery, postoperative serum magnesium level of <0.8 mmol/L, postoperative duration of mechanical ventilation, and postoperative intra-aortic balloon pump use. The model's performance was good in the validation group. The area under the receiver operating characteristic curve was 0.761 (95% confidence interval: 0.737-0.784). Observations and predictions from the model agreed well in the calibration plot. The model was also clinically useful based on decision curve analysis., Conclusions: It is feasible by using the model to identify persistent AKI after cardiac surgery in patients with normal baseline renal function who experienced postoperative AKI, which may aid in patient stratification and individualized precision treatment strategy., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Normal-renal calciphylaxis (NRC) is a devastating calcific vasculopathy characterised by refractory wounds. It is more likely to be misdiagnosed because of the absence of renal insufficiency. Failure to effectively control may lead to rapid deterioration and ultimately death. However, current knowledge of it is still inadequate., Objectives: To provide a relatively comprehensive review of NRC., Methods: Nine electronic medical databases including PubMed, Web of Science, Embase, the Cochrane Library and so on were searched from inception to April 1, 2022. Articles in which calciphylaxis was diagnosed in patients with normal renal function were included., Results: Totally 140 articles were retrieved with 187 patients (median age, 62 years [IQR, 49.63 ~ 75.70 years]; 83.42% female; 84.5% Caucasian). Vitamin K antagonism (43.32%) and diabetes (39.57%) accounted for most of the concomitant factors. Cutaneous presentations were the most common. Pathological confirmation was made in 97.86% of patients with an accuracy of 99.45%. Multidisciplinary therapeutic strategies were usually implemented while the final prognosis was not ideal, with a 6-month mortality rate of 21.10% and a 1-year mortality rate of 27.52%., Conclusion: NRC is an under-recognised disease caused by a variety of factors; meanwhile, multidisciplinary efforts are required to inform diagnostic and therapeutic decisions., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Augmented renal clearance presents as super-renal function with enhanced renal perfusion and glomerular hyperfiltration in many critically ill infants. This study was to compare vancomycin clearance (CL) between critically ill infants with augmented renal clearance and with normal renal function and to optimize the vancomycin dosage. Data were retrospectively obtained from infants treated in intensive care units. Population pharmacokinetics analysis was conducted using nonlinear mixed-effects model software. A total of 66 critically ill infants were included: 47 infants with augmented renal clearance and 19 infants with normal renal function. The median doses of vancomycin for infants with augmented renal clearance and with normal renal function were 48 and 47 mg/kg/day (P > .05), respectively. The median CL in infants with augmented renal clearance was increased 1.96-fold compared with infants who had normal renal function (0.98 versus 0.5 L/h, P < .001). Simulations indicated that the recommended dosage of 60, 70, 80, 90, and 100 mg/kg/day would be appropriate in critically ill infants with an estimated glomerular filtration rate (eGFR) of 130-149, 150-169, 170-189, 190-209, and >210 mL/min/1.73 m 2 , respectively. Doses of 70 and 75 mg/kg/day were recommended for infants with augmented renal clearance and gestational ages of 27-32.9 and 33-39 weeks, respectively. Doses of 70, 75, 80, and 90 mg/kg/day were recommended for infants with augmented renal clearance and weights of 2.0-2.9, 3.0-3.9, 4.0-4.9, and 5.0-6.0 kg, respectively. In conclusion, the typical vancomycin dosage is insufficient for critically ill infants with augmented renal clearance. Premature infants and infants of low weight with augmented renal clearance need individualized dosing regimens to obtain an adequate area under the serum concentration time curve over 24 h/minimum inhibitory concentration ratio., (© 2022, The American College of Clinical Pharmacology.)

Background: The study aimed to construct a clinical model based on preoperative data for predicting acute kidney injury (AKI) following cardiac surgery in patients with normal renal function., Methods: A total of 22,348 consecutive patients with normal renal function undergoing cardiac surgery were enrolled. Among them, 15,701 were randomly selected for the training group and the remaining for the validation group. To develop a model visualized as a nomogram for predicting AKI, logistic regression was performed with variables selected using least absolute shrinkage and selection operator regression. The discrimination, calibration, and clinical value of the model were evaluated., Results: The incidence of AKI was 25.2% in the training group. The new model consisted of nine preoperative variables, including age, male gender, left ventricular ejection fraction, hypertension, hemoglobin, uric acid, hypomagnesemia, and oral renin-angiotensin system inhibitor and non-steroidal anti-inflammatory drug within 1 week before surgery. The model had a good performance in the validation group. The discrimination was good with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.726-0.753). The calibration plot indicated excellent agreement between the model prediction and actual observations. Decision curve analysis also showed that the model was clinically useful., Conclusions: The new model was constructed based on nine easily available preoperative clinical data characteristics for predicting AKI following cardiac surgery in patients with normal kidney function, which may help treatment decision-making, and rational utilization of medical resources.

Background: Critically ill adults have Augmented Renal Clearance, (ARC) decreasing the systemic circulation of drugs with predominant renal elimination. The phenomenon of ARC is crucial for antimicrobial drugs as it hinders the therapeutic response and aids the development of antimicrobial resistance. The present study was conducted to assess the impact of ARC on an Intensive Care Unit (ICU) of a tertiary care hospital., Methods: This was a prospective observational study carried out in critically ill patients with normal serum creatinine without any history of renal disease. Details on their demographic characteristics, clinical diagnoses, laboratory parameters including trough levels of vancomycin and gentamicin, ICU length of stay, and clinical outcomes (discharged alive/death) were obtained. Creatinine clearance (Crcl) was estimated from 24-hour urine creatinine. Monte Carlo simulation test with 100000 iterations was used for predicting serum vancomycin trough levels with the observed Crcl., Results: Eighty patients were recruited in the study of which 52.5% had ARC. Patients in younger age and body weight were observed with a trend to have ARC. No significant differences were observed in any of the drug classes prescribed between patients with and without ARC, including the systemic antimicrobials. Although the observed serum trough levels of vancomycin in patients with ARC did not differ significantly from those without ARC, Monte Carlo simulation predicted that 90% of patients with ARC were likely to have trough levels between 5.63 and 7.85 mg/dl, while those without ARC may have it between 7.75 to 9.82 mg/dl., Conclusion: A significant proportion of critically ill adults exhibit ARC and such patients are more likely to achieve lower trough concentrations of vancomycin than recommended. All critically ill adults with normal serum creatinine have to be screened for ARC using urine creatinine as soon as possible for appropriate adjustment in the dosage regimen of antimicrobials with predominant renal elimination., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30-0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (P linearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013., Competing Interests: None

Purpose: To measure normal renal stiffness in adults, taking into account regional variation, hydration, and urinary status., Methods: Thirty-six healthy volunteers were examined by tomoelastography based on MR elastography at four frequencies, from 40 to 70 Hz and multifrequency shear wave speed recovery. Regional wave speeds were derived for the medulla, cortex (inner cortex and outer cortex), and renal pelvis, and examined for age-related effects. Subgroups were repeatedly examined for reproducibility, amount of prior water drinking, and urinary status. Variations in renal perfusion were simulated ex vivo using a porcine kidney subjected to venous water inflow at different pressures., Results: Shear wave speed (stiffness) of renal parenchyma was 2.46 ± 0.12 m/s (inner cortex: 2.91 ± 0.17 m/s; outer cortex: 2.52 ± 0.11 m/s; medulla: 2.15 ± 0.08 m/s) without side differences and a tendency toward softening with age (P = 0.028). Corresponding intraclass correlation for reproducibility coefficients were 0.78 (inner cortex: 0.80; outer cortex: 0.81; medulla: 0.80). Water drinking resulted in slightly higher values in inner cortex and lower values in medulla (both P = 0.039), which was consistent with the results in perfused specimens. A full bladder led to higher renal pelvis stiffness (P = 0.004), whereas renal parenchyma remained uninfluenced. Stiffness of the porcine renal cortex increased with venous inflow pressure, whereas medulla stiffness decreased., Conclusions: Tomoelastography provides full field of view maps of renal stiffness with highly detailed resolution and sensitivity to physiological effects related to age and fluid-solid tissue interactions. These basic data could be used to compare pathological conditions in the future. Magn Reson Med 79:2126-2134, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Introduction: Cystatin C has been suggested as a sensitive marker of renal function. A high level of cystatin C is related to cardiovascular disease and stroke in elderly patients. We investigated the relationship between levels of cystatin C and early neurological deterioration with acute ischaemic stroke in elderly patients without chronic kidney disease., Patients and Methods: We evaluated a total of 771 elderly patients (mean age, 72.2; male, 59.0%) without chronic kidney disease who were admitted following acute ischaemic stroke between March 2010 and January 2015. The patients were divided into four groups based on the quartiles of serum cystatin C values. Early neurological deterioration was defined as an increase of ≥2 points from the baseline National Institutes of Health Stroke Scale score during the 7 days following onset. We compared the clinical characteristics and cystatin C concentrations between patients with and without early neurological deterioration., Results: Eighty-six patients (11.2%) experienced early neurological deterioration. The percentage values of the higher (third and fourth) quartiles were significantly higher in the early neurological deterioration group (30.2% vs. 24.4% and 34.9% vs. 23.8%, P  = 0.002). After adjustment for covariates, higher cystatin C levels were independently associated with a higher risk of early neurological deterioration: odds ratio (95% confidence interval) for second quartile 1.59 (0.70-3.58), third quartile 2.75 (1.25-6.04), fourth quartile 3.12 (1.36-7.16); P for trend 0.026., Discussion and Conclusions: This study demonstrated that cystatin C concentrations in elderly patients without chronic kidney disease were associated with early neurological deterioration following acute stroke. This suggests that cystatin C level could be a useful predictor for early neurological deterioration following acute stroke., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The treatment of baclofen overdose is primarily supportive. There have been case reports of hemodialysis being used in patients with chronic kidney disease with baclofen overdose. A case report of hemodialysis in a baclofen-overdose patient with normal renal function is presented. Review of literature has also been provided.