Tubular Secretion Markers, Glomerular Filtration Rate, Effective Renal Plasma Flow, and Filtration Fraction in Healthy Adolescents.
Ontology highlight
ABSTRACT:
SUBMITTER: Seegmiller JC
PROVIDER: S-EPMC7568071 | biostudies-literature | 2020 Sep-Oct
REPOSITORIES: biostudies-literature
Publications
Tubular Secretion Markers, Glomerular Filtration Rate, Effective Renal Plasma Flow, and Filtration Fraction in Healthy Adolescents.
Seegmiller Jesse C JC Wolfe Brian J BJ Albtoush Nansy N Melena Isabella I Gross Susan P SP Vinovskis Carisa C Ix Joachim H JH Bjornstad Petter P
Kidney medicine 20200807 5
Similar Datasets
Project description:Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6, is indicated for metastatic breast cancer treatment. Reversible increases in serum creatinine levels of ~15-40% over baseline have been observed following abemaciclib dosing. This study assessed the in vitro and clinical inhibition of renal transporters by abemaciclib and its metabolites using metformin (a clinically relevant transporter substrate), in a clinical study that quantified glomerular filtration and iohexol clearance. In vitro, abemaciclib inhibited metformin uptake by organic cation transporter 2, multidrug and toxin extrusion (MATE)1, and MATE2-K transporters with a half-maximal inhibitory concentration of 0.4-3.8 μM. Clinically, abemaciclib significantly increased metformin exposure but did not significantly affect measured glomerular filtration rate, serum neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin-C, or the urinary markers of kidney tubular injury, NGAL and kidney injury molecule-1.
| S-EPMC6465099 | biostudies-literature
Project description:The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.
| S-EPMC7341488 | biostudies-literature
Project description:Our objective is to monitor glomerular filtration rate (GFR)during the perioperative phase of patients undergoing robotic surgery for rectum or large bowel cancers. We will use both a single injection and a continuous infusion of iohexol to measure kidney function for 72 hours after surgery.
| 2300288 | ecrin-mdr-crc
Project description:BackgroundAlthough proximal tubular secretion is the primary mechanism of kidney drug elimination, current kidney drug dosing strategies are on the basis of eGFR.MethodsIn a dedicated pharmacokinetic study to compare GFR with tubular secretory clearance for predicting kidney drug elimination, we evaluated stable outpatients with eGFRs ranging from 21 to 140 ml/min per 1.73 m2. After administering single doses of furosemide and famciclovir (metabolized to penciclovir), we calculated their kidney clearances on the basis of sequential plasma and timed urine measurements. Concomitantly, we quantified eight endogenous secretory solutes in plasma and urine using liquid chromatography-tandem mass spectrometry and measured GFR by iohexol clearance (iGFR). We computed a summary secretion score as the scaled average of the secretory solute clearances.ResultsMedian iGFR of the 54 participants was 73 ml/min per 1.73 m2. The kidney furosemide clearance correlated with iGFR (r=0.84) and the summary secretion score (r=0.86). The mean proportionate error (MPE) between iGFR-predicted and measured furosemide clearance was 30.0%. The lowest MPE was observed for the summary secretion score (24.1%); MPEs for individual secretory solutes ranged from 27.3% to 48.0%. These predictive errors were statistically indistinguishable. Penciclovir kidney clearance was correlated with iGFR (r=0.83) and with the summary secretion score (r=0.91), with similar predictive accuracy of iGFR and secretory clearances. Combining iGFR with the summary secretion score yielded only modest improvements in the prediction of the kidney clearance of furosemide and penciclovir.ConclusionsSecretory solute clearance measurements can predict kidney drug clearances. However, tight linkage between GFR and proximal tubular secretory clearance in stable outpatients provides some reassurance that GFR, even when estimated, is a useful surrogate for predicting secretory drug clearances in such patients.
| S-EPMC8054886 | biostudies-literature
Project description:BACKGROUND:A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. RESULTS:Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. CONCLUSIONS:The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.
| S-EPMC5943199 | biostudies-literature
Project description:BackgroundsRecently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown.MethodsWe retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR.ResultsIn the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope.ConclusionThere were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.
| S-EPMC8237122 | biostudies-literature
Project description:BackgroundObesity is one of the causes of glomerular hyperfiltration. Studies on the relationship between body fat content and glomerular hyperfiltration have been limited to special children. Therefore, we aimed to evaluate the correlation between skinfold thickness, which represents body fat content, and estimated glomerular filtration rate (eGFR).MethodsThe cross-sectional study included 6655 participants (3532 boys and 3123 girls; age: 12 - 17.99 years); data was obtained from the National Health and Nutrition Examination Survey (NHANES; 2001-2010). The independent variables were subscapular skinfold thickness and triceps skinfold thickness. The dependent variable was eGFR. We used multivariate linear regression models to evaluate their associations and also performed subgroup analyses.ResultsAfter adjusting for age, standing height, race, family income, blood urea nitrogen and uric acid variables, multivariate regression analysis identified that triceps skinfold thickness and subscapular skinfold thickness were positively correlated with eGFR and glomerular hyperfiltration in boys. In subgroup analyses stratified by age and body mass index, triceps skinfold thickness was also associated with glomerular hyperfiltration in boys. There was a linear relationship between triceps skinfold thickness and eGFR in boys (β = 0.389, P < 0.001) and girls (β = 0.159, P = 0.0003).ConclusionsTriceps skinfold thickness and subscapular skinfold thickness are positively correlated with eGFR and glomerular hyperfiltration in US male adolescents. In all adolescents, there is a linear relationship between triceps skinfold thickness and eGFR.
| S-EPMC8897831 | biostudies-literature
Project description:BackgroundEquations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values.ObjectiveTo develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.DesignCross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates.SettingResearch studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006.Participants8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES.MeasurementsGFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age.ResultsIn the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%).LimitationThe sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR.ConclusionThe CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.Primary funding sourceNational Institute of Diabetes and Digestive and Kidney Diseases.
| S-EPMC2763564 | biostudies-literature
Project description:BackgroundThe glomerular filtration rate (GFR) assesses the function of all nephrons, and the single-nephron GFR assesses the function of individual nephrons. How the single-nephron GFR relates to demographic and clinical characteristics and kidney-biopsy findings in humans is unknown.MethodsWe identified 1388 living kidney donors at the Mayo Clinic and the Cleveland Clinic who underwent a computed tomographic (CT) scan of the kidney with the use of contrast material and an iothalamate-based measurement of the GFR during donor evaluation and who underwent a kidney biopsy at donation. The mean single-nephron GFR was calculated as the GFR divided by the number of nephrons (calculated as the cortical volume of both kidneys as assessed on CT times the biopsy-determined glomerular density). Demographic and clinical characteristics and biopsy findings were correlated with the single-nephron GFR.ResultsA total of 58% of the donors were women, and the mean (±SD) age of the donors was 44±12 years. The mean GFR was 115±24 ml per minute, the mean number of nephrons was 860,000±370,000 per kidney, and the mean single-nephron GFR was 80±40 nl per minute. The single-nephron GFR did not vary significantly according to age (among donors <70 years of age), sex, or height (among donors ≤190 cm tall). A higher single-nephron GFR was independently associated with larger nephrons on biopsy and more glomerulosclerosis and arteriosclerosis than would be expected for age. A higher single-nephron GFR was associated with a height of more than 190 cm, obesity, and a family history of end-stage renal disease.ConclusionsAmong healthy adult kidney donors, the single-nephron GFR was fairly constant with regard to age, sex, and height (if ≤190 cm). A higher single-nephron GFR was associated with certain risk factors for chronic kidney disease and certain kidney-biopsy findings. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).
| S-EPMC5664219 | biostudies-literature
Project description:IntroductionGlomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease.MethodsAll available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25" (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values.ResultsA total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N = 332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine versus cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p < 0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p = 0.06 to p = 0.016).ConclusionExcellent agreement between CKD-Epi equations indicates continued use of serum creatinine alone for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.
| S-EPMC11250572 | biostudies-literature