Glomerular Filtration Rate In Children Research Articles

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

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

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

Serum uric acid concentration is associated with lower glomerular filtration rate in children undergoing kidney transplantation.

The relationship between serum concentration of uric acid (UA) and chronic kidney disease is complex due to many confounding variables. There is currently debate over whether hyperuricemia acts as a marker of kidney disease or as an independent risk factor. To test the impact of serum UA concentration on the estimated glomerular filtration rate (GFR) of children undergoing kidney transplantation. Prospective longitudinal study of children and adolescents after kidney transplantation. We analyzed clinical, anthropometric, and laboratory data at pre-transplant and 1, 3, and 6 months after transplant. We developed models of repeated measures analysis, using the generalized estimating equations technique for the outcome evolution of the estimated GFR at 1, 3 and 6 months. High serum UA concentration at 1 and 3 months was modeled as the main exposure variable. We included 103 transplant patients. In a model adjusted for time, recipient sex and age, the occurrence of acute rejection episodes, and the estimated glomerular filtration at baseline, the trajectory of GFR exhibited an inverse relationship with UA (β = -7.1, 95% CI: -11.5 to -2.6, p < .01). Serum UA increase was associated with lower graft function over time.

Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia

BackgroundSickle cell disease is the most common inherited blood disorder in humans and constitutes a major public health burden. It is a multisystemic condition with long-term renal complications. Early detection of sickle cell nephropathy and initiation of appropriate interventions are associated with improved survival and quality of life. This study aimed to compare the cystatin C-derived estimated glomerular filtration rate (GFR) of the study groups and also, to correlate the clinical features of chronic kidney disease (CKD) with decreased GFR in children with sickle cell anaemia (SCA).MethodsThis hospital-based cross-sectional analytic study recruited 86 SCA subjects in steady-state and 86 age and sex-matched healthy HbAA controls aged 1–14 years who attended the Paediatric Haematology and Outpatient clinics of Federal Medical Centre Bida over six months. Data were collected using a semi-structured questionnaire, and participants’ length/height, weight, and blood pressure were measured using standard procedures. Blood samples were drawn for serum cystatin C assay via the sandwich enzyme-linked immunosorbent assay (ELISA) technique. Filler’s equation was used to calculate the glomerular filtration rate.ResultsThere was a significant difference in the mean cystatin C-derived GFR between the two groups, i.e. 116 ± 30mL/min/1.73m2 vs. 106 ± 24mL/min/1.73m2 for the SCA and control groups, respectively (p = 0.017). The prevalence of supernormal GFR (i.e. GFR > 140mL/min/1.73m2) and decreased GFR (i.e. GFR < 90mL/min/1.73m2) was 19.8% and 22.1%, respectively, in children with SCA. There was no significant association between the age at diagnosis of SCA, blood transfusions, blood pressure, packed cell volume and presence of peripheral oedema with decreased GFR in the study subjects.ConclusionsSupernormal GFR is common in children with SCA and there is no significant association between clinical features of CKD with decreased GFR. Regular evaluation of renal function is, however, recommended in children with SCA for early detection and treatment of renal complications in order to halt the progression to end-stage kidney disease (ESKD).

Prospective validation of an equation based on plasma cystatin C for monitoring the glomerular filtration rate in children treated with cisplatin or ifosfamide for cancer.

We recently proposed an equation to estimate the glomerular filtration rate (GFR) in children with cancer based on plasma cystatin C and serum creatinine levels together with body weight (the "CysPed equation"). The current clinical study reports a prospective evaluation of this equation in 18 children treated by nephrotoxic chemotherapy. The CysPed equation resulted in less bias and greater precision compared to two equations previously proposed equations by Schwartz, with or without plasma cystatin C. Moreover, the decrease in GFR due to chemotherapy was clearly identified by the CysPed equation. This equation may be used to monitor the renal function in childhood cancer units.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

BK Viremia and Changes in Estimated Glomerular Filtration Rate in Children and Young Adults after Hematopoietic Cell Transplantation

Kidney disease in allogeneic hematopoietic cell transplantation (HCT) recipients is associated with increased mortality rates. BK virus (BKV) viremia has been associated with kidney dysfunction in pediatric HCT recipients; however, few studies have investigated longer-term kidney outcomes in association with BKV in this population. Here we assessed the relationship between BK viremia and changes in estimated glomerular filtration rate (eGFR) in children in the first year post-HCT. We selected 136 patients age ≤26 years who underwent HCT in 2007 to 2018 at a single center and had plasma BK viral load data available at 2 time points, weeks 4 to 7 post-HCT and weeks 10 to 13 post-HCT from prospectively collected stored plasma samples. A total of 272 samples were analyzed for BKV using quantitative PCR. We used multivariate linear models to determine the association of BK viremia and change in eGFR by 1 year post-HCT. Forty percent of the patients (54 of 136) had BKV detection in weeks 4 to 7, 13% of whom (7 of 54) had a BK viral load of ≥10,000 copies/mL, and 46% (62 of 136) had BKV detected in weeks 10 to 13, 34% (21 of 62) of whom had a BK viral load of ≥10,000 copies/mL. The mean decline in eGFR was 25.73 mL/min/1.73 m2 by 1 year post-HCT. In multivariate models, a BK viral load of ≥10,000 copies/mL during weeks 4 to 7 was associated with a mean decline in eGFR of 30.6 mL/min/1.73 m2 (95% confidence interval, -55.94 to -5.17; P=.019) compared with a BK viral load <10,000 copies/mL. In adjusted analyses, a high BK viral load in the blood (≥10,000 copies/mL) was associated with a significant decline in eGFR by 1 year post-HCT.

Glomerular filtration rate in children with juvenile idiopathic arthritis

Today, it is proved that kidney injury in children with juvenile idiopathic arthritis (JIA) is characterized by a subclinical course and most often remains undiagnosed. One of the main methods to diagnose kidney lesions is determination of estimated glomerular filtration rate (eGFR). The aim of the study was to determine the most optimal method for eGFR evaluation in children with JIA by comparing different calculation methods based on serum creatinine (original Schwartz formula, Counahan-Barratt formula), serum cystatin C (cystatin C-based equation and Hoek formula). Materials and methods. Eighty children with JIA were examined. Serum creatinine level was determined twice (first and third month of study) by the colorimetric kinetic Jaffe reaction, serum cystatin C concentration was evaluated once, in the third month of the study by enzyme immunoassay. We used methods of variation statistics. Results. Parameters of eGFR by cystatin C-based equation 2012 compared to the original Schwartz formula and Counahan-Barratt formula amplified the rate of eGFR disorders by 81.3 % (p &lt; 0.001) and 47.3 % (p &lt; 0.001) in the first month of the study and by 81.3 % (p &lt; 0.001) and 55.0 % (p &lt; 0.001) in the third month, respectively. A similar comparison of the results of Hoek formula with Schwartz and Counahan-Barratt formula showed that according to Schwartz formula, a decrease in the GFR was 41.3 % less frequent (p &lt; 0.001) in both the first and third month. Counahan-Barratt formula in the first study of serum creatinine showed a difference in eGFR compared to Hoek formula by 7.5 % (p &lt; 0.05). During the second study of serum creatinine, the frequency of eGFR reduction according to Counahan-Barratt formula was detected by 15.0 % less often than according to Hoek method (p &lt; 0.09). Conclusions. Changes in renal function differ depending on the formula of eGFR evaluation. The most optimal method to determine eGFR in children with JIA is Hoek formula based on serum cystatin C. In case of limited ability to analyze serum cystatin C, Counahan-Barratt formula based on serum creatinine can be used.

POS-548 GLOMERULAR FILTRATION STATE OF CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS ACCORDING TO Cys-C INDICATORS

According to modern literature reveiw, it is believed that about 8% of children with juvenile idiopathic arthritis (JIA) have chronic kidney disease. Subclinical kidney damage in JIA remains undiagnosed in real clinical practice. Kidney damage can manifest itself as a complication of the underlying disease or, as a consequence, its long-term treatment.The structure of renal pathology in JIA is represented by secondary amyloidosis, glomerulonephritis, tubulo-interstitial nephritis. We investigated the level of cystatin C (Cys-C) in the blood of 80 children with JIA. The age of the subjects was from 3 to 17 years. The calculation of the glomerular filtration rate (GFR) was carried out twice (the first and third months of the study) on the basis of the concentration of Cys-C and creatinine in serum according to the methods: Hoek F.J. et al. (2003), Equation based on cystatin C (2012), Schwartz and Counahan-Barratt (2012). Cys-C averaged 0.886 ± 0.1495 (0.84; 0.79-0.98) μg / ml. The average GFR according to the 2012 equation based on cystatin C was 81.04 ± 12.129 (82.92; 71.74-88.53) ml / min / 1.73 m2, which is significantly lower than with the same GFR calculated using the method Hook - 88.81 ± 14.948 (91.05; 77.32- 98) ml / min / 1.73 m2, p <0.01. The percentage below normal GFR calculated using the 2012 equation based on cystatin C was twice that calculated using Hook's formula: 65 (81.3%) versus 33 (41.3%) cases (p <0.001 according to McNemar's test ). Analysis of the frequency of GFR decline, calculated on the basis of creatinine and Cys-C, also revealed a number of significant differences. Thus, the cystatin C-based equation technique compared with Schwartz and Counahan-Barratt 2012 methods overestimated the incidence of GFR abnormalities by 81.3% (p <0.001) and 47.5% (p <0.001), respectively, in the first month of the study and 81 respectively 3% (p <0.001) and 55.0% (p <0.001) in the third month. A similar comparison with Hook's method showed that according to the Schwartz formula, GFR decreased by 41.3% less often (p <0.001) both in the first and in the third month. The Counahan-Barratt formula did not show significant differences in the first study of creatinine (difference 7.5%, p <0.05), and the second study showed that the decrease in GFR according to the Counahan-Barratt was recorded 15.0% less frequently than according to the data on Hook's method - a deviation close to the level of significance, p <0.09. A more subtle method for detecting subclinical kidney damage in children with JIA is to determine the level of cystatin C followed by calculating the glomerular filtration rate, according to Hook's formula. The concentration of Cys-C was directly related to the duration of the use of non-steroidal drugs (ρ = 0.44, p <0.04), thus, the lengthening of their use had a negative effect on GFR (ρ = -0.44, p <0.04) . And, conversely, with an increase in the duration of immunobiological therapy, the level of cystatin C in the blood decreased (ρ = -0.48, p <0.02) and GFR increased (ρ = 0.48, p <0.02). When detecting a decrease in GFR in children with JIA, it is necessary to limit the intake of non-steroidal anti-inflammatory drugs and increase the basic therapy.

Agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in children with cancer.

Accurate assessment of renal function is important in the care of children with cancer because renal function has implications for anti-tumor medication dosing and eligibility for clinical trials. To characterize agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in a large pediatric oncology cohort. We conducted a retrospective cross-sectional study of children who had both radioisotopic GFR (99mTc-diethylenetriaminepentaacetic acid, or 99mTc-DTPA) and serum labs (creatinine, cystatin C) obtained <7days apart between January 2017 and August 2019. We calculated estimated GFR from serum labsusing published equations and calculated agreement using intraclass correlation coefficient (ICC) and Bland-Altman analysis with univariate regression to define predictors of agreement. We included 272 pairs of data. Mean patient age was (mean ± standard deviation) 7.8±5.7years. Mean radioisotopic GFR was 112±33mL/min/1.73m2. Absolute agreement between radioisotopic GFR and serum estimates was only fair (ICC=0.46-0.58) with a mean difference of -26.6 to +0.12mL/min/1.73m2. For radioisotopic GFR measurements <60mL/min/1.73m2, mean differences were greater, with serum estimates overestimating GFR by a mean of 21.5-39.6mL/min/1.73m2. In multivariable modeling, significant predictors of agreement included age, height, acute kidney injury and tumor type. Sensitivity of serum estimates was 14-29% for a GFR <60mL/min/1.73m2. Agreement between radioisotopic GFR and serum estimates of GFR is only fair and serum estimates of GFR have poor sensitivity for clinically relevant GFR <60mL/min/1.73m2. Radioisotopic measurement of GFR likely remains necessary to assess renal function in pediatric oncology patients with decreased renal function.

Assessment of Cystatin-C level in Newly Diagnosed Iraqi Children with Nephritic Syndrome

BACKGROUND: Nephritic syndrome (NS) is a common kidney disease in children that causes protein leakage from the blood into the urine due to glomerular injury. AIM: The aim of this research was to determine the level of Cystatin-C (CysC) and other biochemical parameters in newly diagnosed NS children in Iraq. PATIENTS AND METHODS: Ninety Iraqi children divided into: 50 children with newly diagnosed NS (28 boys and 22 girls) aged between (4 and 16) years, and 40 healthy control children (20 boys and 20 girls) aged between (5 and 16) years, who were attending Al-Yarmouk Teaching Hospital, Baghdad. RESULTS: There was a significant increase in blood urea, serum total cholesterol (S.TC), and serum low density lipoprotein (S.LDL) and a significant decreased of serum creatinine (S. creatinine), protein/creatinine ratio, serum total bilirubin, serum albumin, and serum high density lipoprotein, while a highly significant increased (p &lt; 0.001) of CysC levels in children with newly diagnosed NS when compared with control group. A significant positive correlation between CysC level versus systolic blood pressure, body mass index, diastolic blood pressure, S.TC, S. LDL cholesterol (S.LDL-C), S. Total Bilirubin, S. Albumin, S. Total protein, and B. urea, while a significant negative correlation was found between CysC level versus serum low density lipoprotein cholesterol and estimated glomerular filtration rate in children with newly diagnosed NS. CONCLUSION: It may come to the conclusion that CysC can be the best predictor of overall efficacy than creatinine and in the diagnosis of any damage to the kidney in children with NS.

ESTIMATION OF THE GLOMERULAR FILTRATION RATE IN CHILDREN WITH HEMOPHILIA.

Estimated glomerular filtration rate (eGFR) is one of the best-performing methods in evaluating kidney function. There are limited data regarding the estimated glomerular filtration rate in children and young adults with hemophilia. The aim of this study was to determine the difference between three commonly used estimated glomerular filtration rate equations in the pediatric population in a cohort of patients with hemophilia. Our prospective study included 36 pediatric patients with moderate or severe hemophilia. eGFR was calculated for each patient using the original creatinine-based "bedside Schwartz" equation, the cystatin C-based equation and the creatinine-cystatin C-based equation. The difference between the equations, calculated using the one-way repeated ANOVA test, was statistically significant (p <0.001), and post hoc analysis found differences between each method. Correlation analysis showed the strongest positive correlation between the bedside Schwartz equation and creatinine-cystatin C-based equation (r=0.866) among the three methods examined. A correlation between the three eGFR methods was present, but with significant differences between them. Due to the observed differences between eGFR in pediatric patients with hemophilia, further research is needed to find the optimal measurement method for eGFR. Nevertheless, we recommend implementing eGFR equations in routine clinical monitoring of pediatric patients with hemophilia.

Accuracy of single intravenous access iohexol GFR in children is hampered by marker contamination

Measurement of glomerular filtration rate (GFR) in children by iohexol injection and blood sampling from the contralateral arm is widely used. A single intravenous access for iohexol injection and subsequent blood sampling has the obvious advantages of being less painful and easier to perform. The purpose of our study was to determine if blood samples drawn from the injection access are feasible and accurate for iohexol GFR (iGFR) measurements. Thirty-one children, median age 10.5 (range 6–17) years, with chronic kidney disease were given a bolus of iohexol followed by extended saline flushing and subsequent venous blood samples collected from the injection access as well as from a cannula in the contralateral arm, the latter serving as the reference method. Paired venous blood samples were collected at four time points (2, 3, 3.5 and 4 h) after the iohexol bolus. Blood sample discarding preceded and saline flushing followed each blood sampling to avoid marker contamination. iGFR based on samples drawn from the injection access at 2 and 3 h showed significantly lower iGFR than measurement from the contralateral arm (p < 0.01). Singlepoint iGFR did not differ significantly after 3–4 repeated procedures of blood discarding and saline flusing (3.5 and 4 h). Despite thorough saline flushing there is still a relatively high risk of falsely low iGFR due to marker contamination in blood samples from the injection site. Hence, blood sampling from a second intravenous access is recommended for routine iohexol GFR measurements in children.Clinical trial registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Glomerular filtration rate in children and young adults with haemato‐oncological disease and infection is best described by three‐compartment iohexol model

Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato-oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single- or two-point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR). Hospitalised patients (0.5-25years) with haemato-oncological disease and infection were included if their eGFR was ≥80ml/min/1.73m2 at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated. Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136ml/min/1.73m2 (74-234) and age 15.1years (0.8-26.0). Three-compartment model with allometric scaling of central, one peripheral compartment and clearance (with power 0.75) to weight fitted the best. Median (range) iGFR was 103ml/min/1.73m2 (68-140). All except one eGFR equation overestimated GFR. Lund-Malmö revised eGFR equation performed the best, followed by Gao equation. Of single- or two-point mGFR formulas, 15 overestimated iGFR. Modified Jacobsson formula at 5.5hours performed the best, followed by Fleming formula at 3hours. In children and young adults with haemato-oncological disease and infection, renal function is best described by iohexol clearance from three-compartment pharmacokinetic model, while eGFR equations and single- and two-point mGFR formulas overestimate iGFR.

Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values

The CKD-EPI creatinine-based estimation equation for glomerular filtration rate (GFR) cannot be used in children, overestimates GFR in young adults, and its combination with the KDIGO recommended pediatric CKiD (Schwartz bedside) equation causes implausible increases in estimated GFR when switching from pediatric to adult care. By establishing sex-specific creatinine growth curves for children and young adults, creatinine levels of children and young adults below age 40 years were adjusted with 40 as assigned age and applied in the CKD-EPI equation. Validation was performed in 4005 children (2-17 years) and 3309 young adults (18-39 years) using metrics based on bias, precision, and accuracy including percentage of estimates within 30% (P30) of measured GFR (mGFR). Comparisons were made with the CKiD and Schwartz-Lyon equations in children. CKD-EPI with age-adjusted creatinine instead of actual age and creatinine led to extensive improvements in bias, precision, and accuracy at all ages, in both sexes and at all levels of mGFR. At mGFR below and above 75 mL/min/1.73m2, the P30 increased from 12% to 75% and 33% to 88% in children, respectively, and from 56% to 73% and 83% to 92% in young adults, respectively. In children adjusted CKD-EPI was more accurate than CKiD, especially above mGFR 75 mL/min/1.73m2 (P30 88% vs. 82%), while Schwartz-Lyon was more accurate than adjusted CKD-EPI at mGFR below 75 mL/min/1.73m2 (P30 81% vs. 75%). Thus, the proposed strategy based on age-adjusted creatinine in children and young adults makes the CKD-EPI equation applicable across the full spectrum of age and kidney function.

Puberty Is Associated with Decline in Estimated Glomerular Filtration Rate in Children with CKD

Puberty Is Associated with Decline in Estimated Glomerular Filtration Rate in Children with CKD

Relationship between Vesicoureteral Reflux and Glomerular Filtration Rate in Children.

Vesicoureteral reflux (VUR) is one of the most common urinary tract anomalies in children and causes renal damage and studies focusing on the effect of VUR on renal function are rare. We recruited 35 primary VUR patients with recurrent urinary tract infection (UTI) and 10 non-VUR patients with recurrent UTI. Contrast-enhanced voiding urosonography (ceVUS) was performed for VUR grading, and renal dynamic imaging was used for evaluating glomerular filtration rate (GFR, mL/min). Standardized GFR (sGFR), namely GFR/BSA (mL·min-1·m-2), was calculated based on the body surface area (BSA). Total sGFR (tsGFR, mL·min-1·m-2) was obtained from the sum of sGFR on the left and right sides of all the children. The risk of renal regurgitation was equal in the unilateral reflux group. The sGFR of children with grade IV (45.74±18.05 mL·min-1·m-2) and grade V (49.67±23.63 mL·min-1·m-2) reflux was significantly lower than that in children with grade III (77.69 ±22.21 mL·min-1·m-2). The renal function compensation of contralateral non-reflux kidney increased in unilateral reflux group, which was higher than that in the control group and level II, IV and V of reflux group respectively. In VUR group of the same grade, sGFR decreased with the age at diagnosis. In unilateral grade V reflux group, the tsGFR was lower than that in the unilateral grade III reflux group (133.51±48.21 vs. 186.87±53.49 mL·min-1·m-2). The patients with VUR of unilateral grade II were significantly older than those with VUR of unilateral grades III and IV. This study indicates that severe VUR is significantly associated with decreased renal function. Therefore, VUR should be diagnosed early and managed individually.

Can estimated glomerular filtration rate replace measured glomerular filtration rate in children receiving platinum agents

Can estimated glomerular filtration rate replace measured glomerular filtration rate in children receiving platinum agents

Estimated glomerular filtration rate in children: adapting existing equations for a specific population.

Creatinine-based glomerular filtration rate (GFR)-estimating equations frequently do not perform well in populations that differ from the development populations in terms of mean GFR, age, pathology, ethnicity, and diet. After first evaluating the performance of existing equations, the aim of this study was to demonstrate the utility of an in-house modification of the equations to better fit a specific population. Estimated GFR using 8 creatinine-based equations was first compared to 2-sample 51Cr-ethylenediaminetetra-acetic acid plasma clearance in non-cancer and cancer groups independently. The groups were then divided into development and validation sets. Using the development set data, the Microsoft® Excel SOLVER add-in was used to modify the parameters of 7 equations to better fit the data. Using the validation set data, the performance of the original and modified equations was compared. Two hundred fifty-six GFR measurements were performed in 160 children. GFR was overestimated in both groups (non-cancer 4.3-22.6ml/min/1.73m2, cancer 17.2-46.6ml/min/1.73m2). The root mean square error (RMSE) was 19.1-21.8ml/min/1.73m2 (non-cancer) and 18.6-20.8ml/min/1.73m2 (cancer). The P30 values were 49.1-73.0% (non-cancer) and 19.6-66.0% (cancer). Modifying the parameters of seven equations resulted in significant improvements in the P30 values in the non-cancer (65.0-85.0%) and cancer (79.6-87.8%) groups. Modifying the parameters of pediatric GFR estimating-equations using a simple Excel-based tool significantly improved their accuracy in both non-cancer and cancer populations. Graphical abstract.

P06 Improving renal function monitoring during chemotherapy- a role for cystatin C?

AimRenal toxicity causes major morbidity following chemotherapy- abnormal iGFRs may be detected in up to 73.7% of patients.1 Creatinine is universally used as a biomarker to track fluctuating function and to calculate surrogate glomerular filtration rate (GFR) in the form of estimating equations.2 There is concern regarding the suitability of creatinine as a biomarker in this population, and it is proposed that cystatin C as a biomarker alone and also included in estimating equations may offer improved clinical suitability and accuracy.3MethodsIn this prospective, longitudinal study over a period of 18 months, 132 combined isotope GFR (iGFR), creatinine and cystatin C measurements were taken from 48 paediatric oncology patients at a Northern Children’s Hospital. Correlation and agreement analysis was performed for both individual biomarkers and estimating equations. Sensitivity data, along with ROC curve analysis was performed for all biomarkers and estimating equations. Data from three identified patients was isolated to examine individual patient variation over time.ResultsCreatinine identified only 1/32 patients with an abnormal iGFR (&lt;90 ml/min/1.73 m2) compared to cystatin C which identified 12/32. Creatinine values and both estimating equations failed to change significantly over a period of declining iGFR though cystatin C did show a significant inverse increase (p&lt;0.05). Bland Altman analysis for both the creatinine and combined equation showed poor agreement (mean difference -64 ml/min/1.3 m2 and -20 ml/min/1.73 m2 respectively). All biomarkers and equations showed poor sensitivity to detect an abnormal iGFR either below 70 ml/min/1.73 m2 or 90 ml/min/1.73 m2. A transformation factor applied to the equations significantly improved the sensitivity and clinical applicability of all equations. The data from three individual patients failed to reveal any significant intra-patient relationships.ConclusionData from this study cannot support the use of creatinine or cystatin C as a single biomarker to monitor renal function in children undergoing chemotherapy. Newer cystatin C and creatinine combined equations, whilst offering statistical superiority, do not offer the clinical superiority to replace iGFR or provide a tool for accurate dose calculations. A transformation factor can be applied to the results gained from the estimating equations to significantly improve the detection of abnormal iGFR, though work in other patient cohorts is needed to support this. Previous work also supported the use of a transformation factor, though application of their transformation factor to this current cohort failed to replicate the 100% sensitivity findings previously demonstrated4. Three patients were identified from the cohort and their paired iGFR and estimated GFR were monitored prospectively, over a period of approximately a year. Significant variation was observed between iGFR and eGFR at each time point for all three patients and therefore personalisation of GFR estimation from baseline iGFR and demographic data could not be proposed. This requires exploration in a larger cohort with the possible inclusion of additional baseline variables.ReferencesCRUK Survival trends over time in Children’s Cancers. 1.2015. https://www.cancerresearchuk.org/health-professional/cancer-statistics/childrens-cancers/survival#heading-Two Accessed 28th March 2019.NICE ( 2013) CG169 Acute kidney injury: Prevention, detection and management of acute kidney injury up to the point of renal replacement therapy.Barnfield, MC, Burniston, MT, Reid, U, et al. Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer. Nuclear Medicine Communications 2013;34:609–614.Dodgshun, AJ, Quinlan, C, Sullivan, MJ. Cystatin C based equation accurately estimates glomerular filtration rate in children with solid and central nervous system tumours: enough evidence to change practice? Pediatric Blood and Cancer 2016;63:1535–1538.