Full Age Spectrum Equation Research Articles

Evaluation of eGFR methods in a sub-Saharan African community-based pediatric population.

Accurate assessment of the estimated glomerular filtration rate (eGFR) plays a pivotal role in the early detection, management, and optimal medication dosing for chronic kidney disease (CKD). However, validation of eGFR, utilizing cystatin C-based equations, is limited in African children and adolescents with CKD. We evaluate the agreement of eGFR equations incorporating both cystatin C and creatinine in this specific population. This community-based study assessed CKD in children (2-15years) using cystatin C and serum creatinine. eGFR agreement with the reference was evaluated with Bland-Altman plots, ROC curves, and Lin's CCC, using the Under-25 serum creatinine-cystatin C equation as the reference standard. Pairwise ROC comparisons assess the statistical differences in estimation equation agreement. Among 666 children (mean age, 7.8 ± 3.8years; 48.6% male), CKD prevalence was 11.6% (95% CI, 9.2-14.2%). Notably, the Chehade equation, using combined biomarkers, aligned best with the reference, displaying the lowest mean deviation (- 0.59; 95% CI, - 1.19 to 0.01), superior agreement (P10, 91.0%; P30, 96.70%), and highest discriminatory power (0.989). In contrast, CKD-EPI 2012 cystatin C had the highest mean deviation (- 35.90) and lowest discriminatory power (0.79). Equations combining creatinine and cystatin C (Schwartz, Chehade, Full Age Spectrum) demonstrated strong positive Lin's CCC with CKiD U25 creatinine-cystatin C, while Bouvet showed a notably weak correlation (Lin's CCC, 0.22). In African children with CKD, the Chehade, CKiD Under 25 creatinine-based equations, and the Full Age Spectrum equations show promise for CKD diagnosis. However, a measured GFR is essential to identifying the most accurate eGFR equation in this population.

Is shrunken pore syndrome also a reality in children?

Shrunken pore syndrome (SPS) is defined as cystatin C-based-eGFR (eGFRcys)/creatinine-based-eGFR (eGFRcreat) <0.6 or 0.7 and is associated with an increased cardiovascular risk. SPS has been described in children, but no link to increased morbi-mortality was demonstrated. Study the prevalence of SPS in a pediatric population using several glomerular filtration rate (GFR) estimating formulas and measured GFR and evaluate the potential link with cardiovascular risk. In 307 renal risk pediatric patients, we studied prevalence of SPS either with CKiDU25creat and cyst or with FAScreat and cyst and EKFCcreat. The characteristics of patients with SPS (defined with Full-age spectrum equation (FAS) and/or European Kidney Function Consortium equation (EKFC)) were compared. The prevalence of SPS varies widely depending on the threshold and the formulas used. Higher C-reactive protein (CRP) and phosphate levels and smaller size are observed in children with SPS defined with FAS and/or EKFC and might be associated with long-term increased cardiovascular risk. Further studies in wider general pediatric populations are warranted.

Evaluation of glomerular filtration rate estimation equations based on serum creatinine in healthy Chinese children and adolescents: a nationwide cross-sectional study

BackgroundSeveral equations for glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) have been proposed for children, but most were developed among patients with kidney disease. The association between...

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear. We conducted a simulation analysis of cysC measured using two reagents standardized against ERM-DA471/IFCC-Gentian cystatin C immunoassay (Gentiancys; GentianAS, Moss, Norway) and Roche Tina-quant Cystatin C Gen.2 (Rochecys; Roche, Mannheim, Germany)-on a Cobas c702 system (Roche) and eGFR generated by eight combinations of four equations: 2012 cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPIcys); the Caucasian, Asian, pediatric, and adult equation (CAPAeq); full age spectrum equation (FASeq); and 2023 cystatin C-based European Kidney Function Consortium equation (EKFCcys). A total of 148 participants (mean age, 60.5±14.5 years; 43% female) were enrolled. The mean cysC was 1.72±1.44 mg/L for Gentiancys and 1.71±1.35 mg/L for Rochecys. Regression analysis showed concordance between the reagents within 0.85-4.40 mg/L when using ±7.61% total allowable error. Lin's concordance correlation coefficient of eGFR, by combining the measuring system and equation, varied from 0.73 to 1.00. The equivalence of cysC values at low concentrations (<0.85 mg/L) between the two reagents was unsatisfactory. Results obtained with different measurement systems could lead to larger differences in eGFR varying with the combination.

Low agreement between various eGFR formulae in pediatric and young adult ADPKD patients.

Young autosomal dominant polycystic kidney disease (ADPKD) patients are becoming the new target population for the development of new treatment options. Determination of a reliable equation for estimated glomerular filtration rate (eGFR) from early stages is needed with the promising potential interventional therapies. Prospective and longitudinal study on a cohort of 68 genotyped ADPKD patients (age range 0-23years) with long-term follow-up. Commonly used equations for eGFR were compared for their relative performance. The revised Schwartz formula (CKiD) showed a highly significant decline in eGFR with aging (- 3.31mL/min/1.73 m2/year, P < 0.0001). The recently updated equation by the Schwartz group (CKiDU25) showed a smaller (- 0.90mL/min/1.73 m2/year) but significant (P = 0.001) decline in eGFR with aging and also showed a significant sex difference (P < 0.0001), not observed by the other equations. In contrast, the full age spectrum (FAS) equations (FAS-SCr, FAS-CysC, and the combined) showed no age and sex dependency. The prevalence of hyperfiltration is highly dependent on the formula used, and the highest prevalence was observed with the CKiD Equation(35%). The most widely used methods to calculate eGFR in ADPKD children (CKiD and CKiDU25 equations) were associated with unexpected age or sex differences. The FAS equations were age- and sex-independent in our cohort. Hence, the switch from the CKiD to CKD-EPI equation at the transition from pediatric to adult care causes implausible jumps in eGFR, which could be misinterpreted. Having reliable methods to calculate eGFR is indispensable for clinical follow-up and clinical trials. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparison of the prevalence of kidney disease by proteinuria and decreased estimated glomerular filtration rate determined using three creatinine-based equations among patients admitted on medical wards of Masaka Regional Referral Hospital in Uganda: a prospective study

BackgroundDespite estimated glomerular filtration rate (eGFR) being the best marker for kidney function, there are no studies in sub-Saharan Africa comparing the performance of various equations used to determine eGFR. We compared prevalence of kidney disease determined by proteinuria of ≥ + 1 and or kidney disease improving global outcomes (KDIGO) eGFR criteria of < 60 ml/minute/1.73m2 determined using three creatinine-based equations among patients admitted on medical ward of Masaka Regional Referral Hospital.MethodsThis was a prospective study conducted among adult patients admitted on medical wards between September 2020 to March 2021. Spot urine samples were collected to assess for proteinuria and blood samples were collected to assess serum creatinine levels. Kidney disease was defined as proteinuria of ≥ 1 + on spot urine dipstick and or KDIGO eGFR criteria of < 60 ml/minute/1.73m2. Estimated glomerular filtration rate was calculated using three creatinine-based equations: a) Full Age Spectrum equation (FAS), b) chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation, c) CKD EPI 2009 (without and with race factor) equation. CKD was determined after followed up at 90 days post enrollment to determine the chronicity of proteinuria of ≥ + 1 and or KDIGO eGFR criteria of < 60mls /minute/1.73m2. We also compared prevalence of CKD determined by KDIGO eGFR criteria of < 60mls /minute/1.73m2 vs age adapted eGFR threshold criteria for defining CKD.ResultsAmong the 357 patients enrolled in the study, KDIGO eGFR criteria of < 60mls / minute determined using FAS and CKD-EPI 2009 without race factor equations and or proteinuria of ≥ + 1 showed the highest overall prevalence of kidney disease at 27.2%.Prevalence of confirmed CKD at 90 days was highest with proteinuria ≥ + 1 and or KDIGO eGFR criteria of < 60mls/min determined using CKD EPI 2009 without race factor Equation (15.1%).ConclusionsUse of KDIGO eGFR criteria of < 60mls / minute /1.73m2 using FAS and CKD-EPI 2009 without race equations identifies the largest number of patients with CKD. Health care systems in sub-Saharan Africa should calculate eGFR using FAS equations or CKD-EPI 2009 without race equations during basic screening and management protocols.

Kidney Function According to Different Equations in Patients Admitted to a Cardiology Unit and Impact on Outcome.

Background: This paper aims to evaluate the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and alternative equations and to assess their predictive power for all-cause mortality in unselected patients discharged alive from a cardiology ward. Methods: We retrospectively included patients admitted to our Cardiology Division independently of their diagnosis. The total population was classified according to Kidney Disease: Improving Global Outcomes (KDIGO) categories, as follows: G1 (estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2); G2 (eGFR 89–60 mL/min/1.73 m2); G3a (eGFR 59–45 mL/min/1.73 m2); G3b (eGFR 44–30 mL/min/1.73 m2); G4 (eGFR 29–15 mL/min/1.73 m2); G5 (eGFR <15 mL/min/1.73 m2). Cockcroft-Gault (CG), CG adjusted for body surface area (CG-BSA), Modification of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS-1), and Full Age Spectrum (FAS) equations were also assessed. Results: A total of 806 patients were included. Good agreement was found between the CKD-EPI formula and CG-BSA, MDRD, BIS-1, and FAS equations. In subjects younger than 65 years or aged ≥85 years, CKD-EPI and MDRD showed the highest agreement (Cohen’s kappa (K) 0.881 and 0.588, respectively) while CG showed the lowest. After a median follow-up of 407 days, overall mortality was 8.2%. The risk of death was higher in lower eGFR classes (G3b HR4.35; 95%CI 1.05–17.80; G4 HR7.13; 95%CI 1.63–31.23; G5 HR25.91; 95%CI 6.63–101.21). The discriminant capability of death prediction tested with ROC curves showed the best results for BIS-1 and FAS equations. Conclusion: In our cohort, the concordance between CKD-EPI and other equations decreased with age, with the MDRD formula showing the best agreement in both younger and older patients. Overall, mortality rates increased with the renal function decreasing. In patients aged ≥75 years, the best discriminant capability for death prediction was found for BIS-1 and FAS equations.

POS-435 CHANGE IN eGFR BY CKD STAGE IN PRIMARY HYPEROXALURIA TYPE 1

The genetic disorder primary hyperoxaluria type 1 (PH1) is marked by an increased hepatic production of oxalate. The resulting hyperoxaluria leads to recurrent nephrolithiasis and nephrocalcinosis which are commonly observed in childhood. About 50% of PH1 patients develop end stage kidney disease (ESKD) by 33 years of age. Clinical trials of potential therapeutic agents are challenging due to disease rarity and time needed to reach hard clinical endpoints (such as ESKD). Thus, slope of eGFR over time is an attractive surrogate endpoint. However, clinical experience suggests that eGFR decline is not uniform across disease course. Thus we looked at the slope of change in eGFR during sequential stages of CKD in a PH1 cohort. PH1 patients enrolled in the Rare Kidney Stone Consortium (RKSC) registry who were >2 years of age, did not have ESKD at diagnosis, and had ≥2 serum creatinine values between dx their last follow up prior to ESKD were studied. eGFR was estimated using the full age spectrum equation. ESKD was defined as the first occurrence of transplant, initiation of dialysis, or eGFR less than 15 ml/min/1.73m2. Absolute change in eGFR over time was estimated by linear regression within each CKD stage, and estimates across CKD stages were compared using GEE models. A total of 129 PH1 patients met inclusion criteria. Seventy (54.3%) were male and 99 (76.7%) were Caucasian. Median [IQR] age at PH1 dx was 8.6 [3.3, 21.6] years. There were 121 patients with follow-up in CKD stage 2; 72 in stage 3a; 41 in stage 3b; and 14 in CKD stage 4. (Table 1) Absolute annual change in eGFR increased with CKD stage (P=0.007 for trend). (Table 1). As hypothesized, eGFR decline was not uniform across CKD stages in this PH1 population, with a higher rate of eGFR decline at CKD stages 3b and 4. Thus, absolute eGFR and CKD stage need to be accounted for when analyzing eGFR slope in this patient group. These data also suggest that measures to prevent GFR decline to < 45 ml/min/1.73m2 are particularly important, as the disease course accelerates thereafter.

Prevalence of Mildly Reduced Estimated GFR by Height- or Age-Related Equations in Young People With Obesity and Its Association with Cardiometabolic Risk Factors

To compare the prevalence of mildly reduced estimated glomerular filtration rate (MRGFR) (eGFR >60 and<90mL/min/1.73m2), calculated by two creatinine-based equations, and its association with cardiometabolic risk factors (CMRF) in youth with overweight (OW)/obesity (OB). This is a multicenter cross-sectional study involving university and non-university hospital pediatrics departments. We enrolled 3,118 youth with OW/OB (5-14years) and 286 healthy normal weight (NW) youth. eGFR was calculated using bedside Schwartz equation (eGFRBSE) and Full Age Spectrum equation (eGFRFAS). In OW/OB group we analyzed the association between eGFR calculated by both equations and CMRF. Uric acid (UA) and birth weight were available in 2,135 and in 1,460 youth. The prevalence of MRGFR was 3.8% in NW versus 7.8% in OW/OB (P=.016) by eGFRBSE, and 8.7% in NW versus 19.4% in OW/OB (P<.0001) by eGFRFAS. eGFRBSE and eGFRFAS identified 242 and 605 young people with OW/OB with MRGFR, respectively. Individuals with MRGFR according with both equations showed lower birth weight, younger age, higher BMI-SDS, non-high-density lipoprotein-cholesterol and UA as compared to those with normal eGFR. To examine whether the eGFRFAS was associated with a worse CMR profile also in the range of normal eGFRBSE, we reclassified young people with normal eGFRBSE (n=2,876) according with eGFRFAS. Out of youth with normal eGFRBSE, 366 (12.7%) presented MRGFR by eGFRFAS and had lower age, higher BMI-SDS, BP and UA than the remaining youth reclassified as normal eGFRFAS. MRGFR is associated with an altered CMR profile in a large sample of young people with overweight (OW)/obesity (OB). The eGFRFAS equation identifies a higher prevalence of youth with MRGFR, compared to eGFRBSE equation.

GFR Estimation After Cystatin C Reference Material Change

IntroductionGlomerular filtration rate (GFR) is routinely estimated with cystatin C. In June 2010, the International Federation of Clinical Chemistry (IFCC) released a certified cystatin C reference material (ERM-DA471/IFCC), and new cystatin C glomerular filtration rate estimation (eGFR) equations were developed with the IFCC standard. Early in 2018, Siemens discontinued their nonstandardized cystatin C reagent kits and replaced them with IFCC-calibrated kits in the US market. The aim of the current study was to assess the effect of IFCC calibration on cystatin C values and corresponding GFR estimations.MethodsCystatin C concentration was measured in 81 pediatric patients using a plasma sample from their nuclear GFR measurement with 99mTc-diethylenetriaminepentaaccetic acid. Calibration curves were generated using Siemens nonstandardized and IFCC-standardized kits to measure paired cystatin C concentrations in each sample. GFR-estimating equations using pre-IFCC and IFCC cystatin C values were compared using Bland-Altman analyses.ResultsThe IFCC-standardized assay resulted in a mean increase in the measured cystatin C value of 24%. Estimating equations consistently overestimated GFR prior to IFCC standardization. Following incorporation of the IFCC standard, the Full Age Spectrum equation demonstrated the best overall performance, whereas the Chronic Kidney Disease in Children (CKiD) equation was more accurate in children with decreased GFR.ConclusionIncorporation of the IFCC standard significantly increased cystatin C values and affected the performance of GFR estimating equations. Clinical laboratories and providers may need to update the equation used for cystatin C–based estimation of GFR following adoption of the IFCC reference standard.

Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.

Vancomycin is eliminated by glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL). This prospective observational study enrolled critically ill patients (2-18 years) receiving intravenous vancomycin at the Children's Hospital of Philadelphia during December 2015-November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours before intravenous vancomycin (baseline) initiation or immediately after enrollment and along with the third pharmacokinetic sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of the estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations. In total, 83 vancomycin levels were obtained from 20 children. The median age was 12.7 years; 6 patients were women. A 1-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of the eGFR calculated using a CysC-based equation significantly improved model fit [reduction in objective function value (OFV) range: -17.191 to -18.704] than bedside Schwartz ([INCREMENT]OFV -12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (-22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/h/kg and volume of distribution = 0.48 L/kg. CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.

Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults

Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults. Population-based cohort study. 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI. Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436). Stroke, MI, and all-cause mortality. HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model. During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred.Independent of UACR, when GFR was estimated using the creatinine- and cystatinC-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m2, the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality. eGFR and UACR categorization based on single assessments; lack of cause-specific death data. eGFR of 45 to 59mL/min/1.73m2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults.

Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data.

The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Cross-sectional analysis with separate pooled data sets for development and validation. Research and clinical studies (n= 13) with measured GFR available. 11251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. No Black patients were included. The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Swedish Research Council (Vetenskapsrådet).

Reassessment of kidney function equations in predicting long-term survival in cardiac surgery.

Chronic kidney disease (CKD) is a risk factor for long-term survival in cardiac surgery. The Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) study, CKD Epidemiology Collaboration (CKD-EPI), revised Lund-Malmö (LM), and full age spectrum equations are used to estimate glomerular filtration rates (eGFR), but each have advantages and disadvantages. Our objective was to determine which equation better predicts long-term survival. Data on 1492 consecutive patients who underwent isolated off-pump coronary artery bypass surgery between September 1996 and December 2008 were prospectively collected. Preoperative and postoperative eGFR were calculated using the five equations and compared using Cox regression analyses and time-dependent receiver operating characteristic (ROC) curves at 10 years. In a Cox regression model after correction for significant predictors of long-term mortality, adjusted hazard ratios (HR) for one standard deviation increase in preoperative eGFR were 0.661 (P < .0001), 0.844 (P = .0166), 0.787 (P = .0002), 0.746 (P < .0001), and 0.717 (P < .0001) for the CG, MDRD, CKD-EPI, LM, and FAS equations, respectively. The areas under the time-dependent ROC curve at 10 years also showed that the CG formula has a better predictive value. Postoperative eGFR at discharge were also significant predictors of long-term mortality (HR = 0.603, P < .0001; HR = 0.725, P < .0001; HR = 0.688, P < .0001; HR = 0.673, P < .0001; HR = 0.632, P < .0001 for the CG, MDRD, CKD-EPI, LM, and FAS equations, respectively). The CG formula was shown to better predict survival in cardiac surgery, though the FAS equation has a comparable prognostic value. Additionally, postoperative eGFR at discharge also predicted long-term survival.

Estimating Glomerular Filtration Rate Using Full Age Spectrum Equation to Assess Kidney Function in Hypertensive Patients: A Cross-sectional Study

Background: Estimated glomerular filtration rate (eGFR) is accepted as the best indicator of kidney function and commonly assessed from serum creatinine (Cr) and cystatin C (Cys-C) based equations. The present cross-sectional, observational study aimed to assess eGFR using a new and validated Full Age Spectrum (FAS) equation and compared with eGFR assessed using old and established equations in hypertensive patients.&#x0D; Materials and Methods: Overall, 60 subjects were recruited for the study, including 30 hypertensive patients and 30 age and sex matched healthy subjects. Serum creatinine and cystatin C were measured using commercial biochemical kits. These levels were used to derive and compare eGFR using our different equations, namely, Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-epidemiology collaboration (CKD-EPI), and FAS equation. Student t-test was used for comparison between two groups and One-way ANOVA test was used to find multiple comparison with-in the hypertensive and control group. Pearson’s Univariate correlation followed by multiple linear regression analysis was applied to find independent predictors of eGFR. All data were analyzed using Sigma-Stat.&#x0D; Results: There was significant difference found in the eGFR levels using different equations in hypertensive subjects as compared to healthy subjects (P&lt;0.01). With–in hypertensive subjects and with-in heathy subjects, a significant difference was also reported (both P&lt;0.01). For FAS-based GFR, age was found as independent predictor of eGFR by all FAS equations. eGFR estimated using Cr based equations resulted in significant difference in categorizing number of subjects into CKD v/s non-CKD depending on their eGFR levels. But there was no difference found for the above in serum cystatin C based equations (P=0.26).&#x0D; Conclusion: Present data showed that eGFR derived using all set of equations resulted in variable eGFR levels. But, use of Cr based equations instead of Cys-C or combine Cr-Cys based equations resulted in wide variation i.e. change in GFR due to change in marker.

Prospects for improved glomerular filtration rate estimation based on creatinine-results from a transnational multicentre study.

BackgroundThe Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.MethodsIn a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation.Results7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%.ConclusionsNone of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

P0656FULL AGE SPECTRUM EQUATION IN THE ESTIMATION OF GLOMERULAR FILTRATION RATE IN RUSSIAN ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Glomerular filtration rate (GFR) is the most important and accurate parameter of kidney function in the course of chronic kidney disease (CKD). Renal or plasma inulin, diethylenetriaminepentaacetate (DTPA), ethylenediaminetetraacetate (EDTA), radiocontrast agents (iohexol, iothalamate) and some other substances clearances are the reference methods for determining GFR. However, these methods cannot be applied routinely because of the inconvenience. Several available methods have been developed to estimate GFR in a simpler manner and at low costs. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is widely used to evaluate the GFR in practice. However, this equation is not accurate for the full age spectrum. In 2016, the new equation, full age spectrum equation, based on the serum creatinine (FAScr), was developed and can be applicable to all ages. However, data on the benefits of using the FAScr-method in different populations are contradictory. In particular, it is unclear whether the FAScr provides any advantages over the CKD-EPI method in adults. In this regards, we attempted to compare data obtained FAScr method with results some non-reference and reference methods in adult Russian population. Method We examined 120 Caucasian patients (M:F - 52:68; age 18-76 year) with CKD 1 - 5 stages. Patients with nephrotic syndrome and congestive heart failure were excluded. GFR (reference method) measured by plasma clearance of 99mTc-DTPA (CDTPA). CDTPA determined by one- compartment model 2-4 h method using a Chantler-Barratt linear correction. Estimation GFRs (eGFR) were established by Cockcroft-Gault creatinine clearance (CG), CKD-EPI (creatinine), FAScr and Modification of Diet in Renal Disease (MDRD) methods. Also, renal creatinine clearance (Ccr; UV/P method) was measured. Only GFRs values corrected on 1.73 m2 body surface area had been use. Results The values of GFR (Mean(SEM)) are: CDTPA 67.0(2.46); FAS 69.7(2.50); CKD-EPI 64.3(2.54); MDRD 60.9(2.62); CG 77.6(3.31); Ccr 85.2(3.40), мл/мин/1.73 m2. MDRD was significantly lower (paired Student t-test with correction on multiply comparison by Benjamini-Hochberg method) than CDTPA (P=0.0024), CG (P=0.0001) or Ccr (P&amp;lt;0.0001) were significantly higher. The bias (CDTPA minus non reference GFR) were: FAS -2.67(1.71); CKD-EPI 2.72(1.58); MDRD 6.12(1.78); CG -10.57(2.51); Ccr -18.22(2.26), ml/min. All biases are significantly differ between themselves (P from 0.00064 to &amp;lt;0.000001). The percentage of P30 of the FAS 81.6(3.5) was not significant differ from P30 of CKD-EPI (78.3(3.8); P=0.524) or MDRD (71.7(4.1); P=0.071). However, P30 of CG (67.5(4.3),%; P=0.01) or Ccr (54.2(5.42),%; P&amp;lt;0,001) were significant lower, than P30 of FAS. There were significant comparable direct correlations between CDTPA and FAS (r=0.764), CKD-EPI (r=0.801), MDRD (r=0.756), CG (r=0.656), Ccr (r=0.749); P&amp;lt;0.00001 in all cases. Conclusion In adult Russian population FAScr-method of GFR estimation had not any advantage over CKD-EPIcr-method.

P0661DIAGNOSTIC VALUE OF FULL AGE SPECTRUM EQUATION AS A PREDICTOR OF MORPHOLOGICAL LESIONS IN PATIENTS WITH GLOMERULONEPHRITIS

Abstract Background and Aims Glomerular filtration rate (GFR) is generally accepted as a best overall index of kidney function. However, it remains controversial to choose the optimal equation to estimate GFR in patients with glomerulonephritis (GN). Recent studies have reported that newly developed full age spectrum equation based on normalized serum creatinine (FASsCr) showed improved validity and was less biased, more accurate than currently recommended sCr-based eGFR equations. Our aim was to assess FASsCr equation as a predictor of various morphological lesions in patients with GN. Method 100 patients [48 female, age Me 39 (27; 54) years] with biopsy proven primary GN and without acute kidney injury, infectious diseases, severe heart failure, respiratory insufficiency, cancer were included in the study. Minimal change disease was diagnosed in 9% of cases based on the results of kidney biopsy, in 28% – focal segmental glomerulosclerosis, in 26% – membranous nephropathy and in 37% – IgA-nephropathy. Serum creatinine (sCr) level was measured by enzymatic method (Uni Cel DxC 800 PRO, «Beckman Coulter»,USA). eGFR was calculated using FASsCr equation. The extent of global glomerulosclerosis (GS) was assessed quantitatively as a sum of full and focal sclerotic glomeruli. Tubulo-interstitial fibrosis (TIF) and tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3 - diffuse tubular and interstitial lesions). All patients consistently were separated into 2 groups according to the degree of each morphological lesion (GS, TIF or TA): “mild” (GS&amp;lt;25% or TIF/TA grade 0 or 1) and “severe” (GS ≥ than 25% or TIF/TA grade 2-3). Results eGFR using FASsCr equation positively correlated (p&amp;lt;0,001 in all cases) with GS (r=0,44), TIF (r=0,64) and TA (r=0,61) and was significantly higher in patients with “mild” GS, TIF and TA (p&amp;lt;0,001) in comparison with “severe” group. Using ROC-analysis all patients were separated (p&amp;lt;0.001) in 2 groups using FASsCr equation according to the degree of morphological lesions (“mild” or “severe”): GS (Sn – 48.8%, Sp – 88.1%, ACC – 72.0%, AUC – 0.696, cut-off value – 47 ml/min/1.73m2), TIF (Sn - 75.4%, Sp – 76.9%, ACC – 76.0%, AUC – 0.815, cut-off value – 72 ml/min/1.73m2), TA (Sn – 65.9%, Sp – 88.8%, ACC – 70.0%, AUC – 0.798, cut-off value – 74 ml/min/1.73m2), (Figure). Conclusion Our results show that FASsCr equation is a significant marker of various morphological lesions in patients with GN. FASsCr equation predominantly can be used as a predictor of mild degree of interstitial sclerosis and tubular atrophy with high diagnostic value. Figure: ROC curves with 95% CI of BM panel for A – GS; B – TIF; C – TA

Evidence for shrunken pore syndrome in children

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the “Shrunken Pore Syndrome” (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFRx was calculated using the full age spectrum equations. The ratio eGFRcys/eGFRcrea was plotted against the error of eGFRBTP(%) (i.e. eGFRBTP-Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFRcys/Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFRx, Cin, error of eGFRx(%) and eGFRBTP/eGFRcrea-ratio. The ratio eGFRcys/eGFRcrea and error of eGFRBTP(%) were positively correlated. The prevalence of SPS by eGFRcys/eGFRcrea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFRcys(%) and eGFRBTP(%) and higher Cin regardless of the definition. Overestimation of eGFRcrea in patients with SPS was only present when using the eGFRcys/eGFRcrea rather than the eGFRcys/Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFRcys/exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism.

Diagnostic Performance of Creatinine-Based Equations for Estimating Glomerular Filtration Rate in Adults 65 Years and Older

Estimating glomerular filtration rate (GFR) is useful in many clinical conditions. However, very few studies have evaluated the performance of GFR-estimating equations in older adults at various degrees of kidney impairment. To determine the performance of plasma-creatinine-based equations Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Lund-Malmö Revised, (LMR), full age spectrum (FAS), and Berlin Initiative Study (BIS) 1 in older adults across a broad spectrum of GFRs. Single-center cross-sectional study performed in France including 2247 participants aged 65 to 90 years who underwent inulin GFR measurements from July 1, 2003, to July 30, 2017, for suspected or established renal dysfunction, for renal risk, before kidney donation, or after kidney transplant. The main outcome measure was GRF measured by inulin clearance. Equation performance criteria considered bias (difference between estimated and measured GFR), precision (interquartile range of the median difference), and accuracy P30 (percentage of estimated GFRs lying between [measured GFR - 30% of measured GFR] and [measured GFR + 30% of measured GFR]). The mean (SD) age of the 2247 participants was 71.5 (5) years and 1192 (53.0%) were male. The difference in median (95% CI) bias was significant between CKD-EPI vs LMR (-4.0 [-4.0 to -3.5 mL/min/1.73 m2; P < .001]) and CKD-EPI vs FAS (-2.0 [-3.5 to -2.5] mL/min/1.73 m2, P < .001) but not significant between CKD-EPI vs BIS 1 (0.0 [-1.5 to 0.5], P = .07, Mood test). In patients aged 65 to 74 years with measured GFR<45 mL/min/1.73 m2, the difference in median P30 (95% CI) was not significant between CKD-EPI vs LMR (P = .08) and CKD-EPI vs FAS (P = .48) but significant vs BIS 1 (P = .004, McNemar test). In subjects 75 years and older, with measured GFR less than 45 mL/min/1.73 m2, LMR and BIS 1 were more accurate than CKD-EPI and FAS (P30 = 74.5 [70.0-79.5] and 73.0 [68.0-78.0] vs 69.0 [64.5-74.0] and 69.0 [65.5-72.0]). In all patients, despite small statistical differences, the performance of CKD-EPI equation was not clinically different from that of LMR, FAS, or BIS 1. In a referral group of patients 65 years and older who had GFR estimated using CDK-EPI, LMR, BIS 1, and FAS equations, a comparison with renal inulin clearance found that none of the equations had a superior diagnostic performance. Each had limitations regarding accuracy.