Estimated Glomerular Filtration Rate Research Articles

Diabetic status and the performances of creatinine- and cystatin C-based eGFR equations.

The estimation of glomerular filtration rate (GFR) is one main tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C, has been proposed. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR) (iohexol or 51Cr-EDTA). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within±30% of mGFR). In the whole population (n=6158), median [IQR] age was 61 [47;72] years, with 45.8% women. Mean mGFR was 60 [39;82] mL/min/1.73m². Compared to non-diabetic individuals (n=5124), diabetic patients (n=1034) were older, more frequently male, heavier, and had lower mGFR. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic but, according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status. We showed that equation combining creatinine and cystatin C present a better performance. If accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more due to differences in GFR levels than to the diabetic status.

Urinary Kidney Injury Molecule 1 and Urinary Monocyte Chemotactic Protein 1 as Novelbiomarkers for Early Detection of Sickle Cell Nephropathy

Abstract Background Sickle cell disease (SCD) is one of the most common genetic disorders, it not onlyhas hematological pathophysiological consequences, but also has systemic pathologicalmanifestations such as Sickle cell nephopathy(SN). There are no randomized control trials thatexamined the utility of screening test for renal disease in individuals with SCD. Aim of the Work To evaluate urinary monocyte chemoattractant protein-1 (MCP-1) and urinarykidney injury molecule 1 (KIM-1) as biomarkers for early detection of sickle cell nephropathy and correlate them with proteinuria and decline in estimate glomerular filtration rate ( eGFR). Patient and Methods This study was a cross sectional study, conducted at Pediatrics Hematology-Oncology Unit at Ain Shams University Children’s Hospital, where 45 children with sickle cell disease were enrolled aged 6 months - 16 years. Urine samples were collected to measure MCP-1and KIM-1 levels and compared to age and sex matched control. Results There was a statistically significant difference found between control group and patients’group regarding the level of MCP-1 in urine as it was found higher in patients than control group with median(IQR) values of 600 pg/ml (300–780) vs. 47.5 pg/ml (30–80, p < 0.001). Regarding the level of KIIM-1 in urine, it was found higher in patients than control group with median (IQR)values of 2.8 ng/ml (1.6–5.6) vs. 0.4 ng/ml (0.4–0.55, p<0.001) respectively. Conclusion Our data shows a distinct biomarker pattern in children with SCD, identifying KIM-1and MCP-1 as two potential biomarkers of early SN and its progression.

Glomerular Filtration Rate in Sick Neonates: A Focus on Cystatin C

Background: The use of creatinine as an endogenous marker of estimated glomerular filtration rate (eGFR) is well-established in clinical practice, despite its limitations. As a step toward limiting this drawback, cystatin C and various biomarkers came into use in determining renal function. In sick neonates, various pathologies may impair renal function thus, underscoring the need for accurate estimation of glomerular filtration rate (GFR). Aims and Objectives: This study aimed at evaluating the use of cystatin C in estimating the GFR of sick neonates in comparison to creatinine. Materials and Methods: A hospital-based descriptive study was conducted at a tertiary center in North Central, Nigeria, for 4 months. One hundred and seventy-three sick neonates admitted into the special care baby unit were recruited. Blood was sampled at admission for determination of serum creatinine and cystatin C levels, while a repeat sample for creatinine was taken 48 hours after. GFR was estimated using the Schwartz formula for creatinine and the Zappitelli equation for cystatin C and compared with an inulin reference. Results: The median (interquartile range [IQR]) eGFR derived from cystatin C was 48.8 (21.0) mL/min/1.73 m2, it was higher than the median creatinine-derived GFR at admission and was of statistical significance. It is also approximated closer to the inulin reference. The median (IQR) eGFR derived from creatinine at admission was 21.2 (21.4) mL/min/1.73 m2. Creatinine-derived eGFR was significantly lower in babies with asphyxia and neonatal sepsis compared to those who did not have these diagnoses. Cystatin C-derived eGFR showed no variation between the various diagnoses. Conclusion: In conclusion, cystatin C is a useful and unbiased determinant of eGFR in sick neonates as compared to creatinine.

Accuracy of glomerular filtration rate estimation using creatinine and cystatin C for identifying and monitoring moderate chronic kidney disease: the eGFR-C study.

Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875). Primary, secondary and tertiary care. Adults (≥ 18 years) with stage 3 chronic kidney disease. Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. This trial is registered as ISRCTN42955626. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Creatinine-based formulas are not ideal to estimate glomerular filtration rate in selected pediatric patients: data from a tertiary pediatric nephrology center.

Evaluating glomerular filtration rate (GFR) remains challenging in pediatrics; new formulas were developed to increase performance of GFR estimation (eGFR). We aimed to evaluate the recently published formulas as applied to another pediatric population. A retrospective study was conducted in a cohort of 307 patients with a "kidney risk" (mean age 12.1 ± 4.5 years, sex ratio 1/1) assessed in a tertiary pediatric nephrology center and a mean measured GFR (mGFR) using plasma iohexol clearance of 85.5 ± 25.3 mL/min/1.73 m2; creatinine levels were measured by IDMS-standardized enzymatic method and cystatin C by immunonephelometry. The following eGFRs were calculated: Schwartz2009, Schwartz-Lyon, CKiDU25creat, and EKFC for eGFR using creatinine (eGFR-creat), CKiDU25cys and FAScys for eGFR using cystatin (eGFR-cys) as well as combined SchwartzCreat-Cys, average (CKiDU25creat-CKiDU25cys), and average (EKFC-FAScys) for eGFR using both biomarkers. The performance of the different formulas was evaluated compared to mGFR by absolute bias measurement and accuracy (p10%, p30%). Results are expressed as mean ± SD. Creatinine-based formulas and especially the new CKiDU25 and EKFC overestimate GFR, even in children with normal kidney function. However, the bias is constant with these two formulas whatever the age group or gender, contrary to the previously published formulas. In contrast, cystatin C-based equations and combined formulas showed good performance in all age groups and all medical conditions with an acceptable bias and p30%. In our pediatric population, the performance of all creatinine-based formulas is inadequate with significant GFR overestimation, mainly in subjects with mGFR > 75 mL/min/1.73 m2. Conversely, cystatin C-based or combined formulas have acceptable performance in patients followed in a tertiary pediatric nephrology unit.

Recommendations for the assessment of glomerular filtration rate in patients with cancer: A position statement and systematic review on behalf of the American Society of Onco-Nephrology (ASON).

e24143 Background: Accurate assessment of glomerular filtration rate (GFR) is crucial to guiding drug eligibility, dose-adjusting systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. To date, there has been a lack of guidance to standardize approaches to GFR estimation in the cancer population based on the available evidence. We aim to present data on the first systematic review (SR) of GFR estimating equations in patients with cancer. Methods: We conducted a SR on behalf of the American Society of Onco-Nephrology (ASON) on the accuracy of equations to estimate GFR in adult patients with cancer, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We required that studies use a reference methodology as comparator involving measured GFR via urinary or plasma clearance of an exogenous filtration marker or carboplatin. Two search strategies focusing on studies using serum creatinine (Cr) and cystatin C (Cys) were developed. Risk of bias and quality assessment was performed for all studies. Results: A total of 39 studies (21,949 patients in total, 19,025 with solid cancers) were included. Studies assessing populations in Europe were most frequent (50%), followed by Asia (27%) and the remaining from Australia/New Zealand and North and South America. Risk of bias and quality assessment allocated 15 studies (38%) as low or very low quality, and 24 (62%) as low-moderate or moderate quality. The most commonly assessed GFR estimating equations included Cockroft-Gault (32 studies), Modification of Diet Renal Disease (MDRD) (24 studies), Chronic Kidney Disese Epidemiology Collaboration Study (CKD-EPI)Cr (22 studies), Wright (13 studies), CKD-EPICys (8 studies), CKD-EPICr-Cys (8 studies), and Jeliffe (8 studies). Given the importance of accurate and timely eGFR assessment and the evidence supporting the performance (i.e., accuracy) of the CKD-EPI incorporating both Cr and Cys, we suggest the use of this equation in patients with cancer (grade 2C). Where Cys is unavailable, CKD-EPICr is the next preferred equation given the supporting data for its performance and widespread availability. Since included studies were moderate quality or lower, the ASON rated the certainty of evidence as low. Also, additional data on clinical outcomes related to the selection of eGFR equations is needed. We suggest measurement of GFR via an exogenous filtration marker in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials (ungraded). Conclusions: Based on the results of this SR, we suggest use of contemporary methods for estimation of GFR (CKD-EPICr-Cys and CKD-EPICr-Cr) and avoidance of older and less accurate formulae such as Cockcroft-Gault.

Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Performance of race-neutral eGFR equations in patients with decompensated cirrhosis.

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol measured GFR(mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985-2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, MDRD-4, MDRD-6, RFH and GRAIL overall and in certain subgroups(ascites, mGFR≤30mL/min/1.73 m2, diagnosis, MELD and gender). We examined bias(difference between eGFR and mGFR), accuracy(p30: eGFR within ±30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the 2nd lowest bias across the entire range of GFR after GRAIL (6.6 vs. 4.6mL/min/1.73 m2, respectively, p<0.001). Accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30=67.8% vs. 67.9%, respectively) that was higher than the other equations (p<0.001). It had a similar performance in patients with ascites, by diagnoses, MELD subgroups, by sex and in non-Black patients. However, it had a relatively higher overestimation in mGFR≤30mL/min/1.73 m2 than most equations (18.5mL/min/1.73m2, p<0.001). Specifically, 64% of patients with mGFR≤30mL/min/1.73m2 were incorrectly classified to a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9mL/min/1.73 m2 that was higher than the alternate equations except RFH (p<0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis given implications for organ allocation and dual organ transplant.

The EKFC equation outperforms the CKD-EPI and CKiD equations for GFR estimation in adolescent and young adult kidney transplant patients.

This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.

#1179 Early change of eGFR predicts long-term renal event in patients with hypertensive chronic kidney disease using a RAS blocker

Abstract Background and Aims The renin-angiotensin-aldosterone inhibitor (RASI) is one of the important medications for chronic kidney disease (CKD) with potential decrease of glomerular filtration rate (GFR) after initiation. There are few studies about the effect of GFR change by the RASI on variations of GFR and albuminuria. Method This observational cohort study was the extension of an open-label, case-controlled randomized clinical trial (NCT01552954) including adult hypertensive CKD patients with estimated GFR ≥30 ml/min/1.73 m2 and random urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine. In the trial phase, the angiotensin receptor blocker (ARB: Olmesartan 40 mg/day) was prescribed to participants after cessation of RASIs for 8 weeks of screening phase. (0-week). Participants had the second visit at 8 weeks after initiation of ARB (8-week) with randomization into the intensive education for low salt diet and the conventional education. Third visit was conducted at 16 weeks after 0-week (16-week). After 27 (19∼38) months later, we recruited participants for the cohort observation and finished at 38 (29∼48) months after 0-week visit. We grouped patients by tertiles of percent change of initial GFR during the first 8 weeks (from 0-week to 8-week) (pcGFRi) and compared the change of UACR from 24-hour urine and estimated GFR during trial and observational period. Results We analyzed data from 174 people finished 38-month observation among 235 participants enrolled for the trial phase. Initial GFR and 24-h urine UACR were 67 ± 24 ml/min/1.73 m2 and 829 ± 829 mg/g cr, respectively. There were −16.0 (−41.5∼−8.1) %, −2.8 (−7.3∼1.6) %, and 8.3 (1.8∼28.4) % pcGFRi in the first tertile group (group 1), the second tertile group (group 2), and the third tertile group (group 3), respectively. There were no differences in age, gender, GFR, 24-hour UACR, and 24-hour sodium excretion among the tertile groups at 0-week visit. The pcGFRi and the tertile group showed positive correlation with GFR change during 16 weeks of the trial, however, were not related to the percent change of 24-hour UACR during the trial phase. They were also positively correlated to the percent change of GFR during whole study period of 38 months (factor B = 8.180 and p-value&amp;lt; 0.001 for the group and factor B = 0.801 and p-value&amp;lt; 0.001 for pcGFRi), although, they did not show relationships with the percent change of 24-hour UACR during whole study period and UACR at last visit. The GFR slopes per year during 38 (29∼48) months were −2.9 (−4.0∼ −1.8), −1.3 (−2.4∼-0.3), and 0.1 (−1.0∼1.2) ml/min/1.73 m2/year in group 1, group 2, and group 3, respectively (p = 0.001 by the ANCOVA test). The relative risks to estimate GFR decrease ≥ 30% during whole study period were 0.237 (0.07∼0.798) (p = 0.020) and 0.035 (0.004∼0.302) (p = 0.035) in group 2 and group 3 compared to group 1, respectively. The AUC to estimate GFR decline ≥ 30% by the pcGFRi was 0.787 (0.685∼0.889, p&amp;lt; 0.001). The cut-off value 7.25% of pcGFRi estimates GFR decline ≥ 30% with 71.4% sensitivity and 70.9% specificity. Conclusion The decline of GFR by initiation of RASI predicts long-term renal event of GFR decline ≥ 30% in users of RASI, strongly. We need to compare the renal outcomes between RASI users with initial decrease of GFR and non-users to make guideline adjusting RASI usage according to initial change of GFR with RASI prescription.

#771 Estimating glomerular filtration rate: does the diabetic status influence the performances of current equations?

Abstract Background and Aims Diabetes is the first cause of chronic kidney disease (CKD) worldwide. The estimation of glomerular filtration rate (GFR) is one main tool to detect CKD. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equations is the most validated in Europe. More recently, another renal biomarker, cystatin C, has been proposed. In the current analysis, we studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. Method Four cohorts from the EKFC dataset were considered in which the diabetic status was available: Lund, Sweden (n = 2,780), Berlin, Germany (n = 654), Créteil, France (n = 466), and Paris, France (n = 2,258). Serum creatinine and cystatin C were measured with calibrated assays. GFR was measured by plasma clearances (mGFR) (iohexol in Lund, Berlin and Créteil and 51Cr-EDTA in Paris). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ±30% of mGFR). As the characteristics of diabetic patients were different, we matched diabetic and non-diabetic patients using the following matching criteria: age (±3 years), sex (equal), mGFR (±3 mL/min/1.73 m²), and BMI (±2.5 kg/m²). Results In the whole population (n = 6,158), median [IQR] age was 61 [47; 72] years, with 45.8% of women. Mean measured GFR (mGFR) was 60 [39; 82] mL/min/1.73 m². Compared to non-diabetic subjects (n = 5,124), diabetic patients (n = 1,034) were older, more frequently males, heavier, had lower mGFR (45 vs 64 mL/min/1.73 m²), and higher creatinine (1.44 vs 1.06 mg/dL; p &amp;lt; 0.0001) and cystatin C (1.67 vs 1.20 mg/L) concentrations. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than single-biomarker equations. Globally, P30 were substantially lower in diabetic patients than in non-diabetic patients (Table). We could match data for 289 females and 546 males. The results in the matched cohorts were quite similar between diabetics and non-diabetics subjects, and this is true for every equation. Conclusion In conclusion, in a large dataset of patients including diabetics and non-diabetics, we showed that the EKFC equations are accurate in diabetic and non-diabetic patients. Combining the creatinine and cystatin C-based equations presents an added value. If accuracy of all equations seems better in non-diabetic than in diabetic subjects, it is probably more due to differences in age and (still more) in GFR levels than to the diabetic status.

#2120 Impact on CKD classification and comorbidities using GFR estimated by European Kidney Function Consortium equation in kidney transplant recipients

Abstract Background and Aims In 2020, European Kidney Function Consortium (EKFC) proposed a new equation that estimates glomerular filtration rate (GFR) in European population. Few studies have compared EKFC with CKDEPI, particularly in kidney transplant (KT) recipients. Chronic Kidney Disease (CKD) classification by KDIGO is used not only by nephrologists who evaluate more parameters of kidney function, but also by every other specialist who are going to be guided mainly by this stage. Our objective is to compare EKFC equation and CKDEPI in classifying CKD in KT patients and its relationship with associated comorbidities. Method We conduct a retrospective observational study including all KT performed at our centre from 1993 to 2022 with survival greater than one year. We collect creatinine, haemoglobin (Hb), phosphorus (P−), potassium (K+), and bicarbonate (Bic) values at three months and one-year post-transplant. We define anaemia as Hb &amp;lt; 11 g/dl, hyperphosphataemia as serum P− &amp;gt; 4.5 mg/dl, hyperkalaemia as serum K+ &amp;gt; 5 mEq/ml, and acidosis as Bic &amp;lt; 22 mEq/L. We calculate estimated GFR (eGFR) using CKDEPI and EKFC equations, classify CKD stage according to KDIGO, and compare both results in terms of correlation and differences. We use Kappa Coefficient and Chi-Square by contingency tables, and ROC curves with homogeneity test for prediction of these comorbidities. We use SPSS and MedCalc as statistics programs. Results We include 968 KT, with median age at the time of transplant 52.75 year [41.25-61.27]. 294 KT (30.4%) are in women. Comorbidity frequencies are depicted in Table 1. ROC analysis shows no significant differences in predicting acidosis at one year, hyperphosphataemia at any time, hyperkalaemia at 3rd month, anaemia at any time, and composite event at any time. We find significant differences in favour to CKDEPI for acidosis at 3rd month (ΔAUC 0.00575 95% CI [0.00182-0.00969]; p = 0.0042) and for hyperkalaemia at one year (ΔAUC = 0.00853 [0.00161-0.0154]; p = 0.0157). Through contingency tables we compare classification into stages, finding very good agreement based on the Kappa coefficient (κ) but significant differences by Chi-Square. With κ = 0.905, EKFC reclassifies 70 patients, 7.23% overall, but not significantly down nor upstaging (31 vs 39). It reclassifies more men than women: 8.46% vs 4.42%. In 10-year age groups, the largest reclassification occurs in the 70-80 years group, a 17.07% with κ = 0.774, all cases upstaged. At one-year eGFR, contingency tables also show a very good agreement based on κ but significant differences by Chi-Square. EKFC reclassifies 83 KT (κ = 0.887), 8.57% overall. It reclassifies 7.48% women and 9.05% men. In 10-year age groups, the largest reclassification occurs in 20-30 years group with 17.24% (κ = 0.767) and 14.81% in 70-80 years (κ = 0.796). All patients in these groups were upstaged. We resume graphically the reclassification of the groups in Fig. 1, observing how EKFC upstages CKD (worsen CKD stage) in high eGFR stages, and downstages CKD in low eGFR stages. Conclusion Estimation of GFR in KT recipients using the new EKFC equation yields similar results to CKDEPI, showing very good agreement for CKD classification although there is a non-negligible percentage of reclassification, which may be clinically relevant in terms of treatment indications and diagnostic tests. It is to a worse CKD stage in high eGFR and to a better stage in low eGFR, and when EKFC reclassification percentage is greater—in the extreme ages of our cohort—it is always by upstaging. Except for minimal differences which we consider clinically inconsequential, we find no significant differences between both equations in discriminating presence of hyperphosphatemia, hyperkalaemia, anaemia or acidosis.

#466 Comparison of CKDEPI vs EKFC equations in estimating glomerular filtration rate in kidney transplant recipients

Abstract Background and Aims In 2020, European Kidney Function Consortium (EKFC) proposed a new equation that estimates glomerular filtration rate (GFR) in European population. Using creatinine and age, as well as CKDEPI, EKFC gives an estimation which has been demonstrated to correlate better to measured GFR, particularly at extreme ages. CKDEPI equation is the most common equation used in our clinical practice. Few studies have compared EKFC with CKDEPI, particularly in kidney transplant (KT) recipients. Our objective is to compare estimation of GFR with EKFC and CKDEPI in KT patients. Method We conduct a retrospective observational study including all consecutive KT performed at our centre from 1993 to 2022 with survival greater than one year, and laboratory tests at third month and one-year post-transplant. Using Creatinine and Age we calculate estimated GFR (eGFR) by CKDEPI and EKFC equations. We compare both results in terms of correlation and agreement in the global sample and classifying by subgroups according to a) Sex, b) Age by 10-year sections, c) Body Mass Index (BMI) as WHO classification and d) presence or absence of Diabetes Mellitus (DM). We use SPSS as statistics program. Results We include 968 KT, depicted in Table 1. CKDEPI and EKFC at 3rd month and EKFC at one-year have a non-normal distribution (Kolmogorov-Smirnov test with p = 0.003, p = 0.035 and p = 0.002, respectively), contrary to normality in CKDEPI at one year (p = 0.058). Levene test for homogeneity of variances shows no differences (3rd month p = 0.102, one year p = 0.165), as well as in subgroups. We perform, besides Mann-Whitney, Student's T-test despite limitations over means without significant differences in any subgroup. Mean global difference at 3rd month is 0.23 ml/min greater by CKDEPI. There are no relevant differences between subgroups related to DM and BMI. We can describe a difference between women (0.85 ml/min) and men (0.05 ml/min), and it is larger in 20-30 years group (3.4 ml/min) and in 70-80 years (2.74 ml/min). As measure of agreement, Intraclass Correlation Coefficient (ICC) shows excellent correlation in all subdivisions (Cronbach's Alpha statistic (CA) &amp;gt; 0.99), without significant decrease in any subgroup; minimum ICC = 0.987 is in 20-30 years group, and maximum ICC = 0.999 in 40-60 years. Bland-Altman plot is shown in Fig. 1, where we appreciate a negative bias in low eGFR against a positive in higher values. Mean global difference at one-year eGFR is 0.25 ml/min greater by CKDEPI. We observe a difference between women (0.75 ml/min) and men (0.04 ml/min), larger in 20-30 years group (2.94 ml/min) and 70-80 years (2.27 ml/min) without significance. ICC shows excellent correlation without significant decrease in any subgroup; minimum ICC = 0.992 is in 20-30 years group, and maximum ICC = 0.999 in 50-60 years. Conclusion We find no significant differences between means in eGFR by CKDEPI and EKFC. We observe a tendency to a greater estimation in women than in men. Both CKDEPI and EKFC equations for eGFR show an excellent concordance in our cohort of KT but differences in scatter analysis in Bland-Altman plot, greater in higher values of eGFR. ICC and CA are both slightly minor in the extreme age groups of our cohort. It matches what described in major studies; these differences may be not clinically relevant in this age range group but are probably greater in patients beyond this range.

Lateral Posterior Method for Depth Correction while Using the Gates Protocol for GFR Estimation: Is it Comparable to the Gold Standard GFR Estimation by Plasma Sampling?

Abstract Background Glomerular filtration rate (GFR) estimation by Gates protocol using the gamma camera for diethylenetriaminepentaacetic acid (DTPA) dynamic renography has not compared well with the gold standard GFR by plasma sampling method. This is because depth of the kidneys is generally not considered. Our aim was to study whether manual depth correction using the skin to middle of kidney distance in lateral view and posterior aspect-lateral posterior method would reduce the bias in the Gates GFR as compared with the gold standard. Materials and Methods Retrospective study of 27 adult prospective renal donors who underwent GFR by plasma sampling and DTPA dynamic renography at Inlaks and Budhrani Hospital, Pune, Maharashtra, India between January 2022 and April 2023. The entire data was statistically analyzed using Statistical Package for Social Sciences (SPSS ver 21.0, IBM Corporation, United States) for MS Windows. Results There is no significant agreement between plasma sampling versus gamma camera method and plasma sampling versus lateral posterior method for depth correction for GFR measurements; however, the evidence of systemic bias is lower for the gamma camera method compared with the lateral posterior method for depth correction as against the plasma sampling method. Conclusion The lateral posterior method for depth correction while using the gamma camera-based Gates protocol is not a reliable method for depth correction in the western Indian adult population with preserved renal function.

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = -0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population.

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ± 0.1 versus 0.8 ± 0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ± 9.9, 94.8 ± 8.6, and 93.4 ± 10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.

Estimation of glomerular filtration rate with cystatin C in the evaluation of cardiovascular risk

Estimation of glomerular filtration rate with cystatin C in the evaluation of cardiovascular risk

The correlation between pentraxin-3, matrix metalloproteinase-9, and estimated glomerular filtration rate in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is diagnosed when there is a sustained decrease in the estimated glomerular filtration rate (EGFR) over a period of more than 3 months. While Pentraxin-3 (PTX-3) and Matrix Metalloproteinase-9 (MMP-9) levels increase during the acute phase of the kidney injury, chronic conditions often exhibit alteration in the epithelial mesenchymal transition (EMT).Objectives: This study aimed to elucidate the correlation between serum PTX-3, MMP-9, and eGFR in patients with CKD. Method: Thirty hypertensive patients with CKD stages 3, 4, and 5, aged between 16 and 65 years, were enrolled in the study (15 males and 15 females). Diagnosis of CKD was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria, utilizing serum creatinine, and CKD-epidemiology Collaboration (CKD-EPI) estimates. Subsequently, serum MMP-9 and PTX-3 levels were quantified. Result: Patients with CKD exhibited significantly higher serum levels of PTX3 and MMP9. Furthermore. a significant negative connection between PTX-3, MMP-9, and EGFR was observed. Additionally, CKD patients displayed a correlation between PTX-3 and MMP-9 concentrations.Conclusion: Plasma levels of PTX-3 and MMP-9 serve as unique, promising, and important markers that contribute to the pathogenesis of CKD.

Utility of Cystatin C-based Equation for the Estimation of Glomerular Filtration Rate in a Pediatric Population.

The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations alongside 3 non-race-corrected (NRC) eGFR equations commonly used in pediatrics in our cohort. mGFR measured following the intravenous injection of tracer Tc-99mDTPA was retrospectively compared with eGFR from these equations in 57 patients (6 months to 22 years) from different races/ethnicities. Ordinary least squares regression analyses were used to assess correlation between the mGFRs and eGFRs. The average mGFR for this cohort was 84.1 mL/min/1.73 m2. The NRC creatinine equations overestimated eGFR across all groups, with the lowest bias for CKiD U25-creatinine (22.59 mL/min/1.73 m2). The best correlations to mGFR, P30, and lowest biases were the CKiD U25-CysC (0.6281, 80.7%, 3.72 mL/min/1.73 m2) and Schwartz CysC (0.6372, 77.2%, -4.68 mL/min/1.73 m2). Overall, both CKiD U25-CysC and Schwartz CysC provide a good estimation of mGFR with the CKiD U25-CysC having the overall best performance compared to mGFR in our study.

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

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. 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 body mass index (BMI). 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 with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry 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. 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.