Accurate Estimation Of Glomerular Filtration Rate Research Articles

Consistency of metabolite associations with measured glomerular filtration rate in children and adults

Abstract Background and hypothesis There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. Methods We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study, and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform, and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < −0.5), we assessed additional variation by age (height in children), sex, race, and BMI. Results A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race, and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates, and nucleotides were more often negatively correlated with mGFR compared to lipids, but there was no association with metabolite molecular weight, LC/MS platform, and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r<−0.5), 27 were consistently not associated with age (height in children), sex, or race. Conclusions The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI, and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.

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.

Should Cystatin C eGFR Become Routine Clinical Practice?

Kidney function assessment is crucial for diagnosing and managing kidney diseases. Glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging. Serum creatinine, a commonly used marker for estimating GFR (eGFR), has limitations in accuracy and sensitivity. Cystatin C, a protein freely filtered by the glomerulus, has emerged as a promising alternative marker for kidney function. It is unaffected by muscle mass and shows stronger associations with cardiovascular disease and mortality than creatinine. Various equations have been developed to estimate GFR using creatinine or cystatin C alone or in combination. The CKD-EPIcreat-cys equation combining both markers demonstrates improved accuracy in GFR estimation, especially for individuals with eGFR values of 45-59 mL/min/1.73 m2. Cystatin C-based estimates of GFR outperform creatinine-based estimates in predicting clinical outcomes and identifying patients at higher risk, particularly in elderly and non-white ethnic groups. Cystatin C offers advantages over creatinine as a marker of kidney function. It is not influenced by non-kidney factors and provides more accurate estimation of GFR, aiding in the early detection of kidney disease and predicting adverse outcomes. Incorporating cystatin C into routine kidney function assessment may improve patient risk stratification and guide clinical decision-making. However, widespread adoption of cystatin C testing requires increased availability and accessibility in clinical laboratories. Further research and implementation efforts are needed to fully realize the potential of cystatin C in kidney function assessment and improving patient outcomes.

Estimating kidney function in patients with cancer: A narrative review.

Accurate evaluation of glomerular filtration rate (GFR) is crucial in Oncology as drug eligibility and dosing depend on estimates of GFR. However, there are no clear guidelines on the optimal method of determining kidney function in patients with cancer. We aimed to summarize the evidence on estimation of kidney function in patients with cancer. We searched PubMed for literature discussing the performance of GFR estimating equations in patients with malignancy to create a table of the evidence for creatinine- and cystatin c-based equations. We further reviewed novel estimation techniques such as panel eGFR, real-time measured GFR, and functional magnetic resonance imaging. The commonly used GFR estimating equations were derived from populations of patients without cancer. These equations may be less applicable in Oncology due to severe sarcopenia, inflammation, and other physiologic changes in patients with cancer. The Cockcroft-Gault equation currently dominates in clinical Oncology despite significant limitations and accumulating evidence for use of the CKD-EPICr formula. Additional considerations in the practice of Oncology include a recently developed equation (CamGFRv2, also called the Janowitz formula) and the use of cystatin c-based equations to overcome some of the barriers to accurate GFR estimation based on creatinine alone. Overall, we suggest using the CKD-EPI equations (either cystatin c or creatinine-based) among patients with cancer in routine clinical practice and measured GFR for patients at a critical threshold for treatment decisions.

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

First experiences with dynamic renal [68Ga]Ga-DOTA PET/CT: a comparison to renal scintigraphy and compartmental modelling to non-invasively estimate the glomerular filtration rate

PurposeThe determination of the glomerular filtration rate (GFR) is decisive for a variety of clinical issues, for example, to monitor the renal function in radionuclide therapy patients. Renal scintigraphy using glomerularly filtered tracers allows combined acquisition of renograms and GFR estimation but requires repeated blood sampling for several hours. In contrast, dynamic PET imaging using the glomerularly filtered tracer [68Ga]Ga-DOTA bears the potential to non-invasively estimate the GFR by compartmental kinetic modelling. Here, we report the, to our knowledge, first comparison of human renal dynamic [68Ga]Ga-DOTA PET imaging in comparison to renal scintigraphy and compare PET-derived to serum creatinine-derived GFR measurements.MethodsDynamic [68Ga]Ga-DOTA PET data were acquired for 30 min immediately after tracer injection in 12 patients. PET and renal scintigraphy images were visually interpreted in a consensus read by three nuclear medicine physicians. The functional renal cortex was segmented to obtain time-activity curves. The arterial input function was estimated from the PET signal in the abdominal aorta. Single-compartmental tracer kinetic modelling was performed to calculate the GFR using complete 30-min (GFRPET-30) and reduced 15-min PET data sets (GFRPET-15) to evaluate whether a shorter acquisition time is sufficient for an accurate GFR estimation. A modified approach excluding minutes 2 to 10 was applied to reduce urinary spill-over effects. Serum creatinine-derived GFRCKD (CKD-EPI-formula) was used as reference standard.ResultsPET image interpretation revealed the same findings as conventional scintigraphy (2/12 patients with both- and 1/12 patients with right-sided urinary obstruction). Model fit functions were substantially improved for the modified approach to exclude spill-over. Depending on the modelling approach, GFRCKD and both GFRPET-30 and GFRPET-15 were well correlated with interclass correlation coefficients (ICCs) from 0.74 to 0.80 and Pearson’s correlation coefficients (PCCs) from 0.74 to 0.81. For a subgroup of patients with undisturbed urinary efflux (n = 9), correlations were good to excellent (ICCs from 0.82 to 0.95 and PCCs from 0.83 to 0.95). Overall, GFRPET-30 and GFRPET-15 were excellently correlated (ICCs from 0.96 to 0.99 and PCCs from 0.96 to 0.99).ConclusionRenal [68Ga]Ga-DOTA PET can be a suitable alternative to conventional scintigraphy. Visual assessment of PET images and conventional renograms revealed comparable results. GFR values derived by non-invasive single-compartmental-modelling of PET data show a good correlation to serum creatinine-derived GFR values. In patients with undisturbed urinary efflux, the correlation was excellent. Dynamic PET data acquisition for 15 min is sufficient for visual evaluation and GFR derivation.

Estimates Of Glomerular Filtration Rate in Critically Ill Patients With Sepsis: Comparisons of Different Equations

Introduction: Accurate assessment of glomerular filtration rate (GFR) is important in the critically ill. Kinetic estimate of GFR (keGFR) considers the changes of creatinine, creatinine production rate, and volume of distribution, hence postulated to be a more accurate estimate of GFR, where there are rapidly changing kidney functions. We evaluated the association of the estimated GFR by established equations and keGFR with creatinine clearance (CrCl) measurement. Materials and Methods: This is a prospective observational study of critically ill patients. Inclusion criteria were patients older than 18 years old with sepsis (clinical infection and increase in SOFA score>2), and plasma procalcitonin>0.5ng/ml. Plasma creatinine and Cystatin C (CysC) were measured on admission and 4 hours later, and the eGFR were calculated by the Cockcroft Gault (CG), MDRD, CKD-EPI and keGFR equations, and compared to the CrCl measurement. Results: A total of 70 patients were recruited. eGFR by all 4 equations strongly correlates with CrCl. keGFR had the least bias depicted by the mean differences nearest to zero (-18ml/min). Similarly, keGFRCysC had less bias than eGFRCysC, with mean difference of -21ml/min. eGFRCG had the greatest precision depicted by the narrower SD lines, however the precision of both keGFR were not much difference compared to those of eGFRCG. Conclusions: In critically ill patients with sepsis, keGFRCr and keGFRCysC had the least bias and fair precision when compared to creatinine clearance measurement. In the absence of creatinine clearance measurement, keGFR calculations is useful as surrogate for kidney function.

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients.

Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and body weight on Vd. The best LSS included samples at 0.1-1-9h exhibiting a relative mean prediction error (MPE) (RMSE) = -3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (-3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9hours for the third sample were associated with an increased imprecision. A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

Abstract 10245: Egfr Calculation Without the Race Coefficient Obscures Obesity Related Glomerulopathy in Female Adolescents

Introduction: Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. Hypothesis: We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG). Methods: We created a cohort of women and girls ages 12-21 from the New York Metropolitan area using their longitudinal electronic health records (EHR). Glomerular filtration rate (GFR) was estimated in two ways: I) using the standard age recommended formulae, and II) eGFRr -without a race-specific coefficient. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of ≥135ml/min/1.73m 2 . Results: 7315 Black and 15,102 non-Black women and girls were evaluated for kidney function in parallel to body measures. Hyperfiltration was more frequent in Black compared to non-Black individuals when using standard eGFR but was lower after eliminating the race-specific coefficient. Black race was independently associated with hyperfiltration with standard eGFR calculation (OR=3.43, 95% CI 2.95-3.99) but the association was reversed when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Risk of hyperfiltration was higher for Black individuals across all BMI strata with standard eGFR estimates, but when estimated as eGFRr hyperfiltration risk was reduced for overweight (OR =0.70 95% CI 0.54-0.89) and obese (OR=0.47, 95% CI 0.37-0.60) black participants. Simultaneous removal of the race coefficient and adjustment to individual BSA provided the most accurate estimation of GFR compared to creatinine clearance. Conclusions: Estimated CKD prevalence among Black adolescents and young adults increases following removal of the race coefficient while fewer have evidence of ORG. Removing the race coefficient should be accompanied by adjustment to individual BSA in order to estimate more realistically GFR.

Use of cystatin C to estimate glomerular filtration rate

Glomerular filtration rate (GFR) is routinely estimated using endogenous biomarkers due to the complexity of direct measurement methods. Cystatin C is a protease inhibitor produced in all nucleated cells. It is freely filtered and then catabolized by renal tubular cells. Therefore, plasma concentration of cystatin C depends primarily on GFR. Serum cystatin C is less affected by muscle mass, diet, race, gender and age than creatinine. In the general population, equations to estimate GFR based on cystatin C do not have a better performance than those based on creatinine. However, formulas that combine creatinine and cystatin C are more accurate and precise. Estimation of GFR based on cystatin C could be useful in populations in which creatinine value may be biased, such as people with extremely low or high muscle mass, cirrhosis and chronic cardiorenal syndrome. Due to its higher cost in comparison to creatinine, we recommend measuring cystatin C on these clinical situations and when a more accurate estimation of GFR is required.

Estimation of piperacillin clearance with different glomerular filtration rate formulas in critically ill children.

Glomerular filtration rate (GFR) is difficult to assess in critically ill children using gold standard method and alternatives are needed. This study aimed to determine the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children, using a published piperacillin pharmacokinetics (PK) population model. All children hospitalized in the paediatric intensive care unit of a single institution who were receiving piperacillin were included. PK were described using the nonlinear mixed effect modelling software MONOLIX. In the initial PK model, GFR was estimated according to the Schwartz 1976 formula. We evaluated a set of 12 additional validated formulas, developed using plasma creatinine and/or cystatin C concentrations, in the building model to assess the lowest between-subject variability for piperacillin clearance. We included 20 children with a median (range) postnatal age of 1.9 (0.1-19) years, body weight of 12.5 (3.5-69) kg. Estimated GFR according to the Schwartz 1976 formula was 160.5 (38-315) mL min-1 1.73 m-2 . Piperacillin clearance was best predicted by the Bouvet combined formula. The combined Bouvet formula was the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children.

A Machine Learning Approach to Estimate the Glomerular Filtration Rate in Intensive Care Unit Patients Based on Plasma Iohexol Concentrations and Covariates.

This work aims to evaluate whether a machine learning approach is appropriate to estimate the glomerular filtration rate in intensive care unit patients based on sparse iohexol pharmacokinetic data and a limited number of predictors. Eighty-six unstable patients received 3250mg of iohexol intravenously and had nine blood samples collected 5, 30, 60, 180, 360, 540, 720, 1080, and 1440min thereafter. Data splitting was performed to obtain a training (75%) and a test set (25%). To estimate the glomerular filtration rate, 37 candidate potential predictors were considered and the best machine learning approach among multivariate-adaptive regression spline and extreme gradient boosting (Xgboost) was selected based on the root-mean-square error. The approach associated with the best results in a ten-fold cross-validation experiment was then used to select the best limited combination of predictors in the training set, which was finally evaluated in the test set. The Xgboost approach yielded the best performance in the training set. The best combination of covariates comprised iohexol concentrations at times 180 and 720min; the relative deviation from these theoretical times; the difference between these two concentrations; the Simplified Acute Physiology Score II; serum creatinine; and the fluid balance. It resulted in a root-mean-square error of 6.2mL/min and an r2 of 0.866 in the test set. Interestingly, the eight patients in the test set with a glomerular filtration rate < 30mL/min were all predicted accordingly. Xgboost provided accurate glomerular filtration rate estimation in intensive care unit patients based on two timed blood concentrations after iohexol intravenous administration and three additional predictors.

Improving accuracy of estimating glomerular filtration rate using artificial neural network: model development and validation

BackgroundThe performance of previously published glomerular filtration rate (GFR) estimation equations degrades when directly used in Chinese population. We incorporated more independent variables and using complicated non-linear modeling technology (artificial neural network, ANN) to develop a more accurate GFR estimation model for Chinese population.MethodsThe enrolled participants came from the Third Affiliated Hospital of Sun Yat-sen University, China from Jan 2012 to Jun 2016. Participants with age < 18, unstable kidney function, taking trimethoprim or cimetidine, or receiving dialysis were excluded. Among the finally enrolled 1952 participants, 1075 participants (55.07%) from Jan 2012 to Dec 2014 were assigned as the development data whereas 877 participants (44.93%) from Jan 2015 to Jun 2016 as the internal validation data. We in total developed 3 GFR estimation models: a 4-variable revised CKD-EPI (chronic kidney disease epidemiology collaboration) equation (standardized serum creatinine and cystatin C, age and gender), a 9-variable revised CKD-EPI equation (additional auxiliary variables: body mass index, blood urea nitrogen, albumin, uric acid and hemoglobin), and a 9-variable ANN model.ResultsCompared with the 4-variable equation, the 9-variable equation could not achieve superior performance in the internal validation data (mean of difference: 5.00 [3.82, 6.54] vs 4.67 [3.55, 5.90], P = 0.5; interquartile range (IQR) of difference: 18.91 [17.43, 20.48] vs 20.11 [18.46, 21.80], P = 0.05; P30: 76.6% [73.7%, 79.5%] vs 75.8% [72.9%, 78.6%], P = 0.4), but the 9-variable ANN model significantly improve bias and P30 accuracy (mean of difference: 2.77 [1.82, 4.10], P = 0.007; IQR: 19.33 [17.77, 21.17], P = 0.3; P30: 80.0% [77.4%, 82.7%], P < 0.001).ConclusionsIt is suggested that using complicated non-linear models like ANN could fully utilize the predictive ability of the independent variables, and then finally achieve a superior GFR estimation model.

Correlation of methods of glomerular filtration rate estimation: Cockcroft–gault equation, modification of diet in renal disease, chronic kidney disease epidemiology collaboration, and DTPA renography in prospective renal donors -a retrospective analytical study

Introduction: The gold standard method for estimating glomerular filtration rate (GFR) in potential donors is diethylenetriaminepentaacetic acid (DTPA) renogram. But DTPA renogram being inconvenient, expensive, and with limited access , hence we need other methods which are noninvasive and provide a comparatively accurate estimation of GFR. Various estimating equations such as Cockcroft–Gault (CG) equation, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are available but have not been well studied or compared to DTPA GFR measurement. Methods: A total of 100 healthy donors (females and males) were studied. All participants underwent 99mTc DTPA renogram, and the GFR obtained was compared with MDRD, CG, and CKD-EPI-estimated GFR. Correlation between variables was estimated by statistical analyses in SPSS software version 18.0, and accuracy of various methods was studied. The data were analyzed by paired t-test, and Pearson's correlation test was used to correlate between two variables. Results: Out of the 100 donors, 79% were females and out of 100 renal recipients, 88% were males. The mean age for donors was 47.27 ± 10.93 years and for recipients was 35.02 ± 11.11 years. The mean GFR (mL/min per 1.73 m2) obtained by DTPA, CG, MDRD, and CKD-EPI was 109.91 ± 20.3, 114.10 ± 21.25, 128.66 ± 22.69, and 108.86 ± 12.72, respectively. The overall mean bias was smallest for CKD-EPI (standard deviation: 18.79). The bias and mean absolute difference between calculated and measured GFR for CKD-EPI, MDRD, and CG were 8.98 and 16.05, −17.97 and 23.26, and −5.76 and 23.29, respectively. There was a positive correlation between GFR by DTPA and GFR by CKD-EPI (0.408) and MDRD (0.399). Conclusions: Despite a wide variation in absolute values of GFR obtained by these methods, CKD-EPI and MDRD showed a positive correlation with DTPA GFR. CKD-EPI had least bias and thus correlated best with DTPA. In potential donors, these equations may be inadequate to replace DTPA for estimating GFR and due to limitations of our study further studies are needed with bigger sample size and longer duration.

Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 μmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study

BackgroundAccurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance.MethodsThe Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2.ResultsParticipants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants’ CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr≥60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex.ConclusionsIn a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.

Automated Region of Interest Detection Method in Scintigraphic Glomerular Filtration Rate Estimation.

The glomerular filtration rate (GFR) is a crucial index to measure renal function. In daily clinical practice, the GFR can be estimated using the Gates method, which requires the clinicians to define the region of interest (ROI) for the kidney and the corresponding background in dynamic renal scintigraphy. The manual placement of ROIs to estimate the GFR is subjective and labor-intensive, however, making it an undesirable and unreliable process. This work presents a fully automated ROI detection method to achieve accurate and robust GFR estimations. After image preprocessing, the ROI for each kidney was delineated using a shape prior constrained level set (spLS) algorithm and then the corresponding background ROIs were obtained according to the defined kidney ROIs. In computer simulations, the spLS method had the best performance in kidney ROI detection compared with the previous threshold method (threshold) and the Chan-Vese level set (cvLS) method. In further clinical applications, 223 sets of 99mTc-diethylenetriaminepentaacetic acid renal scintigraphic images from patients with abnormal renal function were reviewed. Compared with the former ROI detection methods (threshold and cvLS), the GFR estimations based on the ROIs derived by the spLS method had the highest consistency and correlations (r = 0.98, p < 0.001) with the reference estimated by experienced physicians. The results indicate that the proposed automated ROI detection method has great potential in automated ROI detection for accurate and robust GFR estimation in dynamic renal scintigraphy.

Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations in Community-Based Populations.

The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1-3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6-3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR.

025 ESTIMATES OF GLOMERULAR FILTRATION RATE IN THE CRITICALLY ILL WITH SEPSIS

Category: Research in AKI (Basic, translational, clinical including clinical trials) Presenter: Assoc. Prof Azrina Md Ralib Keywords: Glomerular Filtration Rate, Cystatin C, Creatinine Accurate assessment of glomerular filtration rate (GFR) in ICU patients is very important for institution of supportive therapy, preventive therapy, early renal support, drug dosing modification or avoidance of nephrotoxic drugs. Kinetic estimate of GFR (keGFR) takes into account the changes of creatinine over time, creatinine production rate, and the volume of distribution, hence postulated to be a more accurate estimate of GFR in the acute setting, where there are rapidly changing kidney functions as in the critically ill. We evaluated the association of the keGFR with estimated GFR (eGFR) by conventional method. This is an interim analysis of a single centre, prospective observational study of critically ill patients. The study has been registered with the National Medical Research Register (NMRR-14-1897-21447) and has obtained ethics approval. Inclusion criteria were patients older than 18 years old with sepsis, defined as clinical infection and acute increase in SOFA score>2, and plasma procalcitonin>0.5ng/ml. Plasma creatinine and Cystatin C were measured at seven time points, and eGFR were calculated by the Cockcroft-Gault, MDRD, CKD-EPI, and eGFRCysC and they were compared to their keGFR equations. Twenty four patients were recruited so far, of which 10 (41.7%) had AKI. Two patients needed dialysis, and one died. keGFRCr strongly correlated with eGFRCKD-EPI equation in all patients at all time points (all r≥0.76, p<0.0001). On the other hand, keGFRCr only correlated well with eGFRMDRD and eGFRCG in AKI patients but less in patients without AKI. keGFRCysC strongly correlated with eGFRCysC in all patients at all time points (all r≥0.89, p<0.0001) keGFRCr and keGFRCysC were not strongly correlated (min r=0.29) eGFRCKD-EPI distribution had the greatest precision depicted by the narrower SD lines. Similarly, keGFRCysC had higher precision when compared to eGFRCysC. eGFRMDRD and eGFRCG had the least bias depicted by the mean difference nearest to zero. Both eGFRCKD-EPI and eGFRCysC distribution differed significantly from the keGFRCr and keGFRCysC, respectively (Wilcoxon sign rank test, p<0.0001). The new equation, keGFR strongly correlated with the eGFR by the CKD-EPI equation with the highest precision. In the absence of serial plasma creatinine measurement, eGFR is best estimated by the CKD-EPI equation. eGFR of Cystatin C also correlated well with its keGFR. Further study would involve analysis of their association with urinary creatinine clearance.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis.

BackgroundAccurate measurement of renal function in cirrhotic patients is still challenging. To find the best test for the determination of the true glomerular filtration rate (GFR) in cirrhotic patients this study prospectively compared measured (m)GFR, the gold standard, with estimated (e)GFR using equations based on serum levels of creatinine and cystatin C.MethodsGFR was measured by sinistrin clearance using the bolus method in 50 patients with cirrhosis (Child Turcotte Pugh score A, B and C) and 24 age-matched healthy subjects as controls. Measured (m)GFR was compared to eGFR using bias, accuracy 10 % and 30 %, as well as correlation coefficients.ResultsCreatinine-based equations generally overestimated GFR in patients with cirrhosis and showed a bias (average difference between mGFR and eGFR) of −40 (CG), −12 (MDRD) and −9 (CKD-EPI-Cr) ml/min/1.73 m2. Cystatin C-based equations underestimated GFR, especially in patients with Child Turcotte Pugh score C (bias 17 ml/min/1.73 m2for CKD-EPI-CysC). Of these equations, the CKD-EPI equation that combines creatinine and cystatin C (CKD-EPI-Cr-CysC) showed a bias of 0.12 ml/min/1.73 m2 as compared to measured GFR.ConclusionsThe CKD-EPI equation that combines serum creatinine and cystatin C measurements shows the best performance for accurate estimation of GFR in cirrhosis, especially at advanced stages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0188-0) contains supplementary material, which is available to authorized users.