Application of the European Kidney Function Consortium Equation to Estimate Glomerular Filtration Rate: A Comparison Study of the CKiD and CKD-EPI Equations Using the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021).

Background and Objectives: The European Kidney Function Consortium (EKFC) equation has been newly proposed for estimating glomerular filtration rate (eGFR) across the spectrum of age. We compared the EKFC equation with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a large-scale Korean population. Materials and Methods: Using the representative Korean health examination data, the Korea National Health and Nutrition Examination Survey (KNHANES 2008-2021), the records of 91,928 subjects (including 9917 children) were analyzed. We compared the EKFC equation with CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations and investigated their agreement across GFR categories. Results: In the total population, the CKD-EPI 2021 equation yielded the highest eGFR value, followed by the CKD-EPI 2009 and EKFC equations. In children, the distribution of eGFR differed significantly between the EKFC and CKiD equations (p < 0.001), with a wider range of eGFR values found with the CKiD equation. Each equation showed weak or moderate agreement on the frequency of the GFR category (κ = 0.54 between EKFC and CKD-EPI 2021; κ = 0.77 between EKFC and CKD-EPI 2009). The eGFR values found by the EKFC equation showed high or very high correlations with those by the CKiD, CKD-EPI 2009, and CKD-EPI 2021 equations (r = 0.85, 0.97, and 0.97, respectively). As eGFR values increased, bigger differences were observed between equations. Conclusions: This large-scale study demonstrates that the EKFC equation would be applicable across the entire age spectrum in Asian populations. It also underscores that national kidney health would be highly affected by an eGFR equation being implemented. Additional investigation and more caution would be warranted for the transition of eGFR equations.

A fully automatic deep learning-based method for segmenting regions of interest and predicting renal function in pediatric dynamic renal scintigraphy.

OBJECTIVE: Accurate delineation of renal regions of interest (ROIs) is critical for the assessment of renal function in pediatric dynamic renal scintigraphy (DRS). The purpose of this study was to develop and evaluate a deep learning (DL) model that can fully automatically delineate renal ROIs and calculate renal function in pediatric 99mTechnetium-ethylenedicysteine (99mTc-EC) DRS. METHODS: This study retrospectively analyzed 1,283 pediatric DRS data at a single center from January to December 2018. These patients were divided into training set (n = 1027), validation set (n = 128), and testing set (n = 128). A fully automatic segmentation of ROIs (FASR) model was developed and evaluated. The pixel values of the automatically segmented ROIs were calculated to predict renal blood perfusion rate (BPR) and differential renal function (DRF). Precision, recall rate, intersection over union (IOU), and Dice similarity coefficient (DSC) were used to evaluate the performance of FASR model. Intraclass correlation (ICC) and Pearson correlation analysis were used to compare the consistency of automatic and manual method in assessing the renal function parameters in the testing set. RESULTS: The FASR model achieved a precision of 0.88, recall rate of 0.94, IOU of 0.83, and DSC of 0.91. In the testing set, the r values of BPR and DRF calculated by the two methods were 0.94 (P < 0.01) and 0.97 (P < 0.01), and the ICCs (95% confidence interval CI) were 0.94 (0.90-0.96) and 0.94 (0.91-0.96). CONCLUSION: We propose a reliable and stable DL model that can fully automatically segment ROIs and accurately predict renal function in pediatric 99mTc-EC DRS.

Motion-compensated image reconstruction for improved kidney function assessment using dynamic contrast-enhanced MRI.

Accurately measuring renal function is crucial for pediatric patients with kidney conditions. Traditional methods have limitations, but dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a safe and efficient approach for detailed anatomical evaluation and renal function assessment. However, motion artifacts during DCE-MRI can degrade image quality and introduce misalignments, leading to unreliable results. This study introduces a motion-compensated reconstruction technique for DCE-MRI data acquired using golden-angle radial sampling. Our proposed method achieves three key objectives: (1) identifying and removing corrupted data (outliers) using a Gaussian process model fitting with a k -space center navigator, (2) efficiently clustering the data into motion phases and performing interphase registration, and (3) utilizing a novel formulation of motion-compensated radial reconstruction. We applied the proposed motion correction (MoCo) method to DCE-MRI data affected by varying degrees of motion, including both respiratory and bulk motion. We compared the outcomes with those obtained from the conventional radial reconstruction. Our evaluation encompassed assessing the quality of images, concentration curves, and tracer kinetic model fitting, and estimating renal function. The proposed MoCo reconstruction improved the temporal signal-to-noise ratio for all subjects, with a 21.8% increase on average, while total variation values of the aorta, right, and left kidney concentration were improved for each subject, with 32.5%, 41.3%, and 42.9% increases on average, respectively. Furthermore, evaluation of tracer kinetic model fitting indicated that the median standard deviation of the estimated filtration rate ( σ F T ), mean normalized root-mean-squared error (nRMSE), and chi-square goodness-of-fit of tracer kinetic model fit were decreased from 0.10 to 0.04, 0.27 to 0.24, and, 0.43 to 0.27, respectively. The proposed MoCo technique enabled more reliable renal function assessment and improved image quality for detailed anatomical evaluation in the case of bulk and respiratory motion during the acquisition of DCE-MRI.

Assessing the status of European laboratories in evaluating biomarkers for chronic kidney diseases (CKD) and recommendations for improvement: insights from the 2022 EFLM Task Group on CKD survey.

OBJECTIVES: Chronic kidney disease (CKD) is a global health issue, ranking as the third leading cause of death worldwide. CKD diagnosis and management depend on clinical laboratory tests, necessitating consistency for precise patient care. Global harmonization of CKD testing through clinical practice guidelines (CPGs) is recommended. Prior to CPG development, assessing the current CKD testing landscape is crucial. In 2022, the European Federation of Laboratory Medicine (EFLM) conducted an online survey among European laboratories associated with EFLM, evaluating CKD testing practices, including new glomerular filtration rate (GFR) estimation methods. This report summarizes the 2022 survey findings and offers recommendations for improving CKD test standardization. METHODS: An online survey was conducted in November 2022 using a questionnaire hosted on LimeSurvey sent to European laboratories affiliated with the EFLM. The survey results were recorded in Excel files and analysed. RESULTS: The results highlight significant discrepancies among countries in unit expression, methods, cystatin C use, and GFR calculation equations. Additionally, limited attention to pediatric renal biology specifics, varied proteinuria and albuminuria result expressions, and limited awareness of GFR measurement methods through iohexol clearance are noted. CONCLUSIONS: In an effort to enhance the standardization of crucial biomarkers utilized in nephrology for evaluating renal function and diagnosing kidney injuries, the EFLM Task Group on CKD suggests nine practical recommendations tailored for European laboratories. The group is confident that implementing these measures will minimize result expression discrepancies, ultimately leading to enhanced patient care.

Noninvasive Assessment of Diabetic Kidney Disease With MRI: Hype or Hope?

Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1- or T2-weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision-making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break-through are discussed including biological validation of the MRI findings, large-scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

The Current State of Nuclear Nephrology in Modern Medicine.

Glomerular filtration rate (GFR) is the most reliable parameter of renal function. Regarding the complexity of the gold standard inulin clearance, different estimating equations have been developed with CKD-EPI creatinine equation recommended as the most reliable one. In some clinical situations where creatinine based equations might not be valid, alternative methods are needed. Nuclear medicine methods for measuring GFR with 51Cr EDTA and 99mTc DTPA have been widely used for decades. There are different methodologies for the measurement of kidney function with radiopharmaceuticals: urinary clearance, plasma clearance, multiple plasma sampling, slope intercept, single sample plasma equation, slope only, and the gamma camera-based method. Greater precision of measuring GFR is needed in certain clinical situations. The most common are diagnosis and follow up of chronic kidney disease and definition of the beginning of replacement therapy. The assessment of renal function is also important for potential kidney donors. In recent years, with the introduction of new chemotherapeutic drugs and targeted therapy, oncologic patients treated with nephrotoxic drugs have become more commonly referred for measuring GFR. The monitoring of renal function is important during treatment in order to detect the transformation from reversible acute kidney injury to irreversible chronic kidney disease as well as in the cases of renal insufficiency reduce the dosage and prevent accumulation of the drug and avoid dosage related toxic effects. Assessment of kidney function using measured mGFR will be an important milestone in the creation of more accurate and expanding personalized medicine principle in current onconephrology practice.

A New Method for Estimating Glomerular Filtration Rate in Rhesus Macaques (Macaca mulatta).

Late effects of total- or partial-body irradiation include chronic kidney injury (CKI), which increases morbidity and mortality. Glomerular filtration rate (GFR) is the gold standard measure of kidney function. Renal function markers, such as blood urea nitrogen (BUN) and serum creatinine (Cr), may not be higher than reference ranges until 50% or more of nephrons are affected. Currently available methods to measure GFR are difficult and expensive, requiring multiple blood draws or timed urine collections, but their use can provide a framework for the development of simpler GFR estimates. The measurement of iohexol clearance is a validated tool used to determine GFR in veterinary patients. In this study, we aimed to determine if the Schwartz formula as used in human pediatric medicine can estimate GFR in rhesus macaques. We hypothesized that iohexol-GFR would correlate with the Schwartz formula-estimated GFR (eGFR) in irradiated and non-irradiated rhesus macaques. Twelve rhesus macaques [age 5-14 years (mean 7 years); 5 females, 7 males] with a range of BUN levels were selected for comparison to 4 non-irradiated controls (2 females, 2 males). Irradiated animals were divided by BUN into 3 groups: BUN ≤20 mg/dL (n = 4), BUN >20-24 mg/dL (n = 4), and BUN ≥25 mg/dL (n = 4). Baseline serum chemistry and urinalysis were used to assess renal function. For measurement of GFR, macaques were maintained under general anesthesia and received an intravenous injection of iohexol (2 mL/kg, 300 mg I/mL). Whole blood was collected at 10, 30, 60 and 90 min post-iohexol injection. Plasma iohexol concentrations were determined by mass spectrometry. GFR was calculated from the peak iohexol concentration and trapezoidal area under the curve (tAUC). The iohexol-GFR significantly correlated with the Schwartz formula-eGFR. In macaques with renal irradiation doses below 6 Gy, GFR was higher for males than females. GFR was lower in macaques with renal irradiation doses greater than 6 Gy compared to macaques with renal doses less than 6 Gy. We conclude that use of the Schwartz formula can provide a rapid, non-invasive, cost-effective, and accurate estimation of GFR to aid in the clinical assessment of renal function in irradiated rhesus macaques.

Transdermal Measurement of Glomerular Filtration Rate in Preclinical Research.

The measurement of glomerular filtration rate (GFR) is essential to understanding renal physiology, including the monitoring of disease progression and treatment effectiveness. Transdermal measurement of glomerular filtration rate (tGFR) using a miniaturized fluorescence monitor in combination with a fluorescent exogenous GFR tracer has become a common technique to measure GFR in the preclinical setting, especially in rodent models. It allows for close to real-time measurement of GFR in conscious unrestrained animals and overcomes several limitations of other GFR measures. Its widespread use is reflected by published research articles and conference abstracts from different research fields, including in the assessment of new and existing kidney therapeutics, evaluation of nephrotoxicity, screening of novel chemical or medical agents, and fundamental understanding of kidney function.

Impact of Particulate Matter With an Aerodynamic Diameter <2.5 µm Concentration on Postoperative Renal Function in Living Kidney Donors.

BACKGROUND: Ambient air pollution has become 1 of the most important public health issues worldwide. In particular, particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) is a fatal component of air pollution. We aimed to analyze whether perioperative exposure to PM2.5 is associated with the deterioration of renal function in living kidney donors. METHODS: This study was conducted on 232 kidney donors with postoperative 2-year glomerular filtration rate (GFR). The GFR was determined by serum creatinine-based method using the Modification of Diet in Renal Disease equation and radionuclide-based method using 99mTc-DTPA renal scintigraphy. Perioperative exposure to PM2.5 was calculated using data from the AIRKOREA System. Multiple linear and logistic regression analyses were performed to estimate the associations between mean PM2.5 concentration and postoperative 2-year GFR. RESULTS: Postoperative Modification of Diet in Renal Disease-estimated GFRs of kidney donors with low PM2.5 concentrations were significantly higher than those of those with high PM2.5 concentrations. A 1-µg/m3 increase in mean PM2.5 concentration was associated with decreased GFR by 0.20 mL/min/1.73 m2. In addition, a 1-µg/m3 increase in mean PM2.5 concentration was associated with an 11% increased risk of chronic kidney disease stage ≥3 at 2 years after donor nephrectomy. CONCLUSION: In patients who underwent donor nephrectomy, exposure to PM2.5 negatively affects renal function and is positively associated with the prevalence of chronic kidney disease.

Avaliação da função renal em coelhos utilizando anti inflamatórios não esteroidais (aines) / Evaluation of renal function in rabbits using non-steroidal anti-inflammatory (aines)

Introdução: Rins são órgãos vitais para o funcionamento do organismo, fazendo parte do sistema excretor e osmorregulador, cujas funções consistem em realizar a filtração do sangue e excretar produtos finais de diversos metabolismos, além de produzirem hormônios, fundamentais para o corpo humano. Com isso em mente, destaca-se que uma causa comum para o surgimento de doenças renais crônicas é o uso exacerbado de medicamentos anti inflamatórios. Objetivo: Relacionar, por meio da análise de creatinina e a taxa de filtração glomerular, a real influência do uso de anti-inflamatórios não esteroidais na função renal. Materiais e Métodos: Estudo experimental, realizado com 8 coelhos com maturidade reprodutiva e peso superior a 1kg, tendo sido escolhidos devido às limitações impostas para animais de pequeno porte, como ratos e camundongos, em exames laboratoriais e de imagem. Resultados: Divididos em 4 grupos, com 2 coelhos em cada um deles, cada qual recebeu um anti-inflamatório não esteroide (AINE) correspondente, administrados por via oral (suspensão). Os coelhos 1 e 2 receberam Ibuprofeno, 3 e 4 Diclofenaco, 5 e 6 Nimesulida e 7 e 8 Cetoprofeno. A avaliação da função renal deu-se pela dosagem periódica da creatinina sérica e a taxa de filtração glomerular, medida por cintilografia renal dinâmica em clínica de medicina nuclear. Os coelhos (grupos 1 e 7) tiveram índices aumentados de creatinina, vindo a óbito por miopatia, e o do grupo 8 teve pneumonia. Após 42 dias de uso da medicação, 5 coelhos apresentaram valores de creatinina considerados normais. Conclusão: Conseguiu-se, por meio do experimento, demonstrar que, apesar de os anti-inflamatórios não esteroidais não necessariamente constituírem risco renal significativo, é importante utilizar esses fármacos com cautela, tendo em vista as alterações evidenciadas no estudo

Introduction: Kidneys are vital organs for the functioning of the body, being part of the excretory and osmoregulating system, whose functions consist of performing blood filtration and excreting end products of various metabolisms, in addition to producing hormones, fundamental to the human body. With this in mind, it is noteworthy that a common cause for the emergence of chronic kidney diseases is the exacerbated use of anti-inflammatory drugs. Objective: To relate, through creatinine analysis and glomerular filtration rate, the real influence of the use of non-steroidal anti inflammatory drugs on renal function. Materials and Methods: Experimental study, performed with 8 rabbits with reproductive maturity and weight greater than 1kg, and were chosen due to the limitations imposed on small animals, such as rats and mice, in laboratory and imaging tests. Results: Divided into 4 groups, with 2 rabbits in each of them, each of which received a corresponding non-steroidal anti-inflammatory (NSAID) administered orally (suspension). Rabbits 1 and 2 received Ibuprofen, 3 and 4 Diclofenac, 5 and 6 Nimesulida and 7 and 8 Cetoprofen. The evaluation of renal function was performed by periodic measurement of serum creatinine and glomerular filtration rate, measured by dynamic renal scintigraphy in a nuclear medicine clinic. Rabbits (groups 1 and 7) had increased rates of creatinine, coming to obito for myopathy, and group 8 had pneumonia. After 42 days of medication use, 5 rabbits had creatinine values considered normal. Conclusion: It was possible, through the experiment, to demonstrate that, although non steroidal anti-inflammatory drugs do not necessarily constitute significant renal risk, it is important to use these drugs with caution, considering the changes evidenced in the study

Introducción: Los riñones son órganos vitales para el funcionamiento del organismo, formando parte del sistema excretor y osmorregulador, cuyas funciones consisten en filtrar la sangre y excretar productos finales de diversos metabolismos, además de producir hormonas, fundamentales para el cuerpo humano. Con eso en mente, cabe señalar que una causa común para la aparición de la enfermedad renal crónica es el uso exacerbado de medicamentos antiinflamatorios. Objetivo: Relacionar, mediante el análisis de la creatinina y el filtrado glomerular, la influencia real del uso de antiinflamatorios no esteroideos sobre la función renal. Materiales y Métodos: Estudio experimental realizado con 8 conejos en madurez reproductiva y con peso superior a 1 kg, habiendo sido elegidos por las limitaciones impuestas para animales pequeños, como ratas y ratones, en pruebas de laboratorio y de imagen. Resultados: Divididos en 4 grupos, con 2 conejos en cada grupo, cada uno de los cuales recibió un fármaco antiinflamatorio no esteroideo (AINE) correspondiente, administrado por vía oral (suspensión). Los conejos 1 y 2 recibieron Ibuprofeno, 3 y 4 Diclofenaco, 5 y 6 Nimesulida y 7 y 8 Ketoprofeno. La evaluación de la función renal se realizó mediante la medición periódica de la creatinina sérica y la tasa de filtración glomerular, medidos por gammagrafía renal dinámica en una clínica de medicina nuclear. Los conejos (grupo 1 y 7) tenían niveles elevados de creatinina, falleciendo por miopatía, y el del grupo 8 tenía neumonía. Después de 42 días de uso de medicamentos, 5 conejos tenían valores de creatinina considerados normales. Conclusión: Fue posible, a través del experimento, demostrar que, aunque los antiinflamatorios no esteroideos no necesariamente constituyen un riesgo renal significativo, es importante utilizar estos fármacos con precaución, frente a los cambios evidenciados en el estudio

Redressing the Harms of Race-Based Kidney Function Estimation.

This Viewpoint emphasizes the urgency of abolishing race-based medical practices and explains how they have unjustly contributed to racial inequities in clinical care and health outcomes.

Comparison of GFR measurement with a two-blood sample technique using [99mTc]Tc-DTPA vs. creatinine-based equations in potential kidney donors.

INTRODUCTION: Accurate determination of glomerular filtration rate (GFR) is crucial for selection of kidney donors. Nuclear medicine methods are considered accurate in measuring GFR but are not always easily available. The four-variable Modification of Diet in Renal Disease (MDRD4), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Full Age Spectrum (FAS) formulas are common equations for estimating GFR and are recommended for initial assessment of kidney donors. The aim of this study was to evaluate the performance of these GFR estimation equations compared with technetium-99m diethylenetriaminepentaacetic acid ([99mTc]Tc-DTPA) clearance. METHODS: We compared GFR estimation by [99mTc]Tc-DTPA clearance using a two-blood sample method with estimation by MDRD4, CKD-EPI, and FAS creatinine-based equations in a population of healthy potential kidney donors. RESULTS: A total of 195 potential kidney donors (68.2% female; mean age 49 years, range 21-75 years) were included in this study. Mean [99mTc]Tc-DTPA measured GFR (mGFR) was 101.5 ± 19.1 mL/min/1.73 m2. All three equations underestimated the GFR value measured by [99mTc]Tc-DTPA (MDRD4: -11.5 ± 18.8 mL/min/1.73 m2; CKD-EPI: -5.0 ± 17.4 mL/min/1.73 m2; FAS: -8.3 ± 17.4 mL/min/1.73 m2). Accuracy within 30% and 10% of the measured GFR value was highest for CKD-EPI. CONCLUSION: The CKD-EPI equation showed better performance in estimating GFR in healthy potential kidney donors, proving to be a more accurate tool in the initial assessment of kidney donors. However, creatinine-based equations tended to underestimate kidney function. Therefore, GFR should be confirmed by another method in potential kidney donors.

CT volumetry performs better than nuclear renography in predicting estimated renal function one year after living donation.

The evaluation of split renal function (SRF) is a critical issue in living kidney donations and can be evaluated using nuclear renography (NR) or computerized tomography (CT), with unclear comparative advantages. We conducted this retrospective study in 193 donors to examine the correlation of SRF assessed by NR and CT volumetry and compared their ability to predict remaining donor renal function at 1 year, through multiple approaches. A weak correlation between imaging techniques for evaluating the percentage of the remaining kidney volume was found in the global cohort, with an R2 = 0.15. However, the Bland-Altman plot showed an acceptable agreement (95% of the difference between techniques falling within - 8.51 to 6.11%). The predicted and observed eGFR one year after donation were calculated using the CKD-EPI, and CG/BSA equations. CT volume showed a better correlation than NR for both formulas (adjusted R2 of 0.42. and 0.61 vs 0.37 and 0.61 for CKD-EPI and CG/ BSA equations, respectively). In non-nested modeling tests, CT volumetry was significantly superior to NR for both equations. CT volumetry performed better than NR in predicting the estimated renal function of living donors at 1-year, independently from the eGFR equation.

Augmented Renal Clearance in Patients with Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND: Augmented renal clearance (ARC) is a phenomenon that has been demonstrated in many subsets of critically ill patients and is characterized by a creatinine clearance (CrCl) > 130 mL/min. Prior research has examined ARC prevalence in the presence of sepsis, traumatic brain injury, subarachnoid hemorrhage, and intracranial hemorrhage. However, to our knowledge, no studies have examined whether this phenomenon occurs in patients suffering from an acute ischemic stroke (AIS). The objective of this study was to evaluate whether patients experiencing an AIS exhibit ARC, identify potential contributing factors, and examine the precision of current renal clearance estimation methods in patients with AIS experiencing ARC. METHODS: This was a single-center prospective observational study conducted in adult patients admitted to a neurocritical intensive care unit (ICU) at a community hospital. Once consent was gained, patients with an admitting diagnosis of an AIS underwent a 24-h urine collection to assess measured CrCl. The primary end point assessed for ARC, defined as a measured CrCl > 130 mL/min. The secondary end point evaluated length of stay in the neurocritical ICU. RESULTS: Twenty-eight patients met enrollment criteria, and data was analyzed for 20 patients. ARC was present in 35% of enrolled patients. Mathematical estimations of renal function were inadequate in detecting ARC manifestation. Patients experiencing ARC were associated with nonsignificantly shorter ICU length of stay. CONCLUSIONS: ARC appears to manifest in patients with AIS inconsistently. Patients experiencing ARC were associated with nonsignificantly shorter ICU length of stay.

Reference standard analysis of multiple new and old plasma clearance models and renal clearance with special attention to measurement of reduced glomerular filtration rate.

Nine models were evaluated as candidate glomerular filtration rate (GFR) reference standards in three datasets using [51Cr(EDTA)]- or [169Yb(DTPA)]2- anions in 98 studies. Noncompartmental methods formed an upper limit for estimating mass excreted and voluntary urine collection formed a lower limit. For current models and methods, reduced GFR in adults resulted in inflated clearance estimates. Two different logarithmic models with exponential tails were created and may have underestimated reduced clearance. The logarithmic formulae can be used with only two plasma samples, and fit 13 multiple time-samples from 5 min to 24 h with an 8% standard deviation of residuals compared to 20% error for monoexponentials. For shorter times (4 or 5 h) the fit errors decreased but the ratio of errors remained at circa 2.5 times lesser for the logarithmic versus monoexponential models. Adaptively regularised gamma variate, Tk-GV, models that are well documented, but not in common use, were largely contained within the reference extreme values, were unbiased for different levels of clearance and were the only models to be uncorrelated to volume of distribution from mean residence time divided by weight. Using Tk-GV as a candidate reference standard, potentially better methods for routine clinical usage were discussed. Prospective clinical testing, and metabolic scaling of decreased renal function is advised for potential changes to patient triage.

Construct a classification decision tree model to select the optimal equation for estimating glomerular filtration rate and estimate it more accurately.

Chronic kidney disease (CKD) has become a worldwide public health problem and accurate assessment of renal function in CKD patients is important for the treatment. Although the glomerular filtration rate (GFR) can accurately evaluate the renal function, the procedure of measurement is complicated. Therefore, endogenous markers are often chosen to estimate GFR indirectly. However, the accuracy of the equations for estimating GFR is not optimistic. To estimate GFR more precisely, we constructed a classification decision tree model to select the most befitting GFR estimation equation for CKD patients. By searching the HIS system of the First Affiliated Hospital of Zhejiang Chinese Medicine University for all CKD patients who visited the hospital from December 1, 2018 to December 1, 2021 and underwent Gate's method of 99mTc-DTPA renal dynamic imaging to detect GFR, we eventually collected 518 eligible subjects, who were randomly divided into a training set (70%, 362) and a test set (30%, 156). Then, we used the training set data to build a classification decision tree model that would choose the most accurate equation from the four equations of BIS-2, CKD-EPI(CysC), CKD-EPI(Cr-CysC) and Ruijin, and the equation was selected by the model to estimate GFR. Next, we utilized the test set data to verify our tree model, and compared the GFR estimated by the tree model with other 13 equations. Root Mean Square Error (RMSE), Mean Absolute Error (MAE) and Bland-Altman plot were used to evaluate the accuracy of the estimates by different methods. A classification decision tree model, including BSA, BMI, 24-hour Urine protein quantity, diabetic nephropathy, age and RASi, was eventually retrieved. In the test set, the RMSE and MAE of GFR estimated by the classification decision tree model were 12.2 and 8.5 respectively, which were lower than other GFR estimation equations. According to Bland-Altman plot of patients in the test set, the eGFR was calculated based on this model and had the smallest degree of variation. We applied the classification decision tree model to select an appropriate GFR estimation equation for CKD patients, and the final GFR estimation was based on the model selection results, which provided us with greater accuracy in GFR estimation.

Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation : A Cross-Sectional Study.

BACKGROUND: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. OBJECTIVE: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. DESIGN: Cross-sectional study. SETTING: Four U.S. community-based epidemiologic cohort studies with mGFR. PATIENTS: 3223 participants in 4 studies. MEASUREMENTS: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. RESULTS: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR - eGFR) was -0.6 (95% CI, -1.2 to -0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. LIMITATION: Single measurement of mGFR and serum markers without short-term replicates. CONCLUSION: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. PRIMARY FUNDING SOURCE: National Institutes of Health.

Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

BACKGROUND: Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. METHODS: We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. RESULTS: GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. CONCLUSIONS: We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Estimación de la función renal para la dosificación de drogas / Estimation of kidney function to adjust drug dosing

Drug dosing according to renal function is a globally accepted practice whose main purpose is to avoid drug associated toxicity when renal clearance is decreased. Renal function is usually estimated based on creatinine clearance or an estimated glomerular filtration rate (GFR) obtained from one of the available equations based on serum biomarkers. In this review we will analyze the different available methods to adjust the dose of drugs based on GFR, with emphasis on their comparative performance for this objective. Based on this, we will provide some recommendations for drug dosing in chronic and acute renal dysfunction.