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Purpose of Review: This article answers the question of whether creatinine is the best biomarker for monitoring neonatal glomerular filtration rate (GFR) in view of recent advances in measuring neonatal renal function., Recent Findings: We rely largely on serum creatinine for the estimation of GFR in the newborn, even though creatinine is freely exchanged through the placenta. During the first few days of life, the serum creatinine reflects maternal renal function or the maternal creatinine. Back filtration of creatinine in preterm newborns is also a serious limitation. This review summarizes current knowledge on the prenatal and postnatal handling of creatinine as well as that of other, more novel biomarkers of GFR, such as cystatin C (CysC) and β-trace protein (BTP). Only small amounts of CysC cross the placenta, whereas BTP does not cross the placenta at all. However, BTP measurements are not widely available. Recent studies on renal volumetry are also discussed., Summary: Currently, CysC may be the most suitable marker of neonatal renal function, but its availability is still limited, it is more costly, and the best method of reporting acute kidney injury and neonatal estimated GFR remains to be established.

Cystatin C may be a more accurate marker of the glomerular filtration rate (GFR) than creatinine. We evaluated the performance of the creatinine-based abbreviated modification of diet in renal disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and 6 cystatin C-based equations in estimating GFR (eGFR) in a heterogeneous sample of patients. Measured GFR (mGFR) was obtained from the plasma clearance of 99mtechnetium Diethylenetriaminepentaacetic acid in 42 adult patients referred for nuclear GFR testing (January to March 2008). We evaluated the bias, precision, and accuracy of the abbreviated MDRD, CKD-EPI, Filler, Grubb, Hoek, Larsson, Le Bricon, and Rule eGFR equations. Participants had a mean mGFR of 70.9 mL/min/1.73 m2 (range: 22-125 mL/min/1.73 m2), a median age of 57 years (interquartile range: 45, 66), were 62% male, and were 38% liver transplant recipients. Correlation coefficients between eGFRs and mGFR ranged from 0.65 to 0.87 (each P<0.001). The cystatin C-based Hoek equation had the best overall performance with a low bias (-1.4 mL/min/1.73 m2), good precision (13.3 mL/min/1.73 m2), and greatest accuracy, with 93% of values within 30% of mGFR. Although the CKD-EPI equation had the lowest bias (-0.6 mL/min/1.73 m2), it had poor precision (20.7 mL/min/1.73 m2) and low accuracy, with only 69% of values within 30% of mGFR. The Hoek equation remained accurate and had the least bias when patients were grouped according to the history of liver transplantation and the mGFR above or below 60 mL/min/1.73 m2. In this heterogeneous sample, the cystatin C-based Hoek equation performed the best overall, regardless of mGFR level or history of liver transplantation., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background and Objectives: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF)., Design, Setting, Participants, & Measurements: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF (131I-hippurate clearance) to calculate the FF (FF=GFR/ERPF). The eGFRs were calculated using the commonly used Schwartz (creatinine), Filler (CysC), and Benlamri (BTP) formulas. Agreement of the eGFRs with the measured isotope GFRs was assessed by Bland-Altman plots. Correlation analysis was performed using nonparametric tests to compare FF with eGFR-GFR., Results: The 127 children at a median age (with 25th percentile, 75th percentile) of 11.9 (8.5, 14.9) years had a mean 51Cr EDTA-GFR of 100.6±32.1 ml/min per 1.73 m2 and a median 131I-hippurate clearance (ERPF) of 588 (398,739) ml/min per 1.73 m2. Mean FF was 17.7±4.5% with no correlation between the FF and the error (eGFR-GFR) for CysC and BTP eGFR, whereas there was a significant negative correlation between the error for Schwartz eGFR and FF., Conclusions: There is a significant negative correlation between the error for the Schwartz eGFR and the FF. CysC and BTP are not affected by differences in FF.

Background: Cystatin C and beta-trace protein (BTP) are low-molecular-weight proteins that have generated interest as alternative endogenous markers of glomerular filtration rate (GFR). Studies examining the effect of demographic, biometric, clinical, and biochemical variables on cystatin C levels have yielded conflicting results, perhaps because of the reliance on inferior methods of GFR determination. The aim of this study is to examine the independent effect of various clinical parameters on serum concentrations of creatinine, cystatin C, and BTP in kidney transplant recipients., Study Design: Cross-sectional study., Setting & Participants: 207 kidney transplant recipients with stable kidney function., Predictors: GFR, age, race, sex, body mass index, albumin level, proteinuria, smoking status, prednisone, and calcineurin inhibitor and mycophenolate mofetil use., Outcomes & Measurements: Multiple linear regression analysis was used to examine the relationship between predictor variables and cystatin C, BTP, and creatinine levels. GFR was measured by using technetium 99m-radiolabeled diethylenetriaminepentaacetic acid clearance., Results: After adjusting for GFR, cystatin C and BTP levels were significantly lower in women compared with men. Greater albumin concentration was associated with significantly lower cystatin C and BTP concentrations. There was a statistically significant, but clinically small, association between body mass index and cystatin C level, but no association between the other demographic variables or medications analyzed., Limitations: Predominantly white population; results may not be applicable to other racial groups., Conclusion: Important nonrenal factors can influence BTP and cystatin C concentrations and need to be considered when interpreting BTP and cystatin C values in kidney transplant patients.

Background: Current clinical guidelines recommend that renal transplant recipients (RTRs) be classified into chronic kidney disease (CKD) stage using a creatinine-based estimate of glomerular filtration rate (GFR). However, creatinine-based equations are inaccurate in RTRs leading to frequent CKD stage misclassification. It is not known whether the classification of CKD stage would be improved using a cystatin C-based estimate of GFR., Methods: We measured (99m)Tc-DTPA GFR, cystatin C and creatinine in 198 stable RTRs. GFR was estimated using cystatin C-based equations (Filler, Le Bricon and Rule) and four creatinine-based equations. We determined the proportion, overall and by CKD stage, that were classified correctly by each equation as compared to the (99m)Tc-DTPA GFR., Results: The Filler equation correctly classified 76% of patients compared to only 65% with the abbreviated modification of diet in renal disease (MDRD) equation and 69% with the Cockcroft-Gault equation. In CKD stages two and four, the Filler equation correctly classified 77% and 60% of patients whereas the abbreviated MDRD equation correctly classified 46% and 93% of patients. The area under the curve by receiver operating curve analysis for overall stage classification was uniformly poor for all equations (0.52-0.56)., Conclusions: The cystatin C-based Filler and Le Bricon GFR estimates classified slightly more patients into the correct CKD stage than the standard creatinine-based equations in stable RTRs although the overall diagnostic accuracies were similar. The differences are modest and prospective studies will be needed to determine if the adoption of these equations for classification would lead to improved recognition of CKD complications or patient care.

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean (99m)Tc-DTPA GFR was 58 +/- 23 ml/min per 1.73 m(2). The cystatin C-based equations of Filler and Le Bricon had the lowest bias (-1.7 and -3.8 ml/min per 1.73 m2), greatest precision (11.4 and 11.8 ml/min per 1.73 m2), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m2. The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

There is controversy about the feasibility of cystatin C (CysC) as a marker of glomerular filtration rate (GFR) post-transplant (Tx). We studied intra-patient variability of CysC in comparison with serum creatinine (SCr) in 20 children (11 males, mean age 11.5 +/- 6.4 yr) with solid organ transplants (14 kidney, four liver, and two combined liver + kidney transplants). The mean age at Tx was 7.0 +/- 5.6 yr. A total of 178 simultaneous SCr and CysC measurements (median 8 per patient) were analyzed. In addition, GFR was calculated using the Schwartz and a novel CysC-based formula. Intra-individual coefficient of variations (CV) was calculated as ratio of standard deviation over mean. The mean CV was significantly lower for SCr (7.71 +/- 4.16%) when compared with CysC (10.27 +/- 4.87, p = 0.04), but was no longer significantly different when excluding patients with a bladder augment. The CV of the GFR estimated by Schwartz formula (7.44 +/- 3.77) was significantly lower than GFR calculated from CysC (12.52 +/- 7.37), p = 0.001. The mean ratio between the Schwartz GFR and the GFR calculated from CysC was 102.6 +/- 12.8%, not significantly different from 100% (p = 0.3796). The only potential confounding factors to explain increased CV after Tx were gender and bladder augmentation, whereas calcineurin inhibitors or steroids did not influence CV. With the limitation of a small number of subjects, our data suggest that the CysC and the CysC-calculated GFR is equivalent but not better than SCr and Schwartz formula. We therefore conclude that measurement of CysC can be used for longitudinal intra-individual follow-up of renal function post-Tx.

Background: Because of the limitations of serum creatinine as a marker of glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys-C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators of reduced GFR., Methods: We obtained serum samples from 225 children (age range, 0.2-18 years) with various renal pathologies who were referred for nuclear medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring), beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP; Roche)., Results: Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73 m(-2)). One hundred fifty children (independent of gender and age) with values >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian distributions of BTP and Cys-C concentrations. The upper reference limits (97.5 percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706, respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r = 0.500 and 0.557, respectively). ROC analysis showed a significantly higher diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP increased the diagnostic sensitivity by approximately 30%, but it was not more sensitive than Cys-C or the Schwartz GFR estimate., Conclusions: BTP is superior to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in children, but it is not better than the Schwartz GFR estimate.

Background: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m2 (chronic kidney disease (CKD) stage 2). We compared agreement and accuracy of the Pierce U25 (ages 2–25), Pottel (ages 2–100), and CKD-EPI (ages 18–100) formulae to GFR measurements. Methods: Post hoc analysis of the three eGFRs compared to 367 99m technetium-diethylene-triamine penta-acetic acid (99Tc DTPA) GFR measurements (240 patients) using 3 sampling points and Brockner/Mørtensen correction (body surface area calculation based on ideal weight) on simultaneous serum creatinine and cystatin C measurements. Results: Overall, the U25 formula performed well with a Spearman r of 0.8102 (95% confidence interval 0.7706 to 0.8435, p < 0.0001) while diagnostic accuracy was low in patients with normal mGFR. The U25 formula reclassified 29.5% of patients with normal mGFR as CKD stage 2; whereas the average of the modified Schwartz formula based on serum creatinine and the Filler formula based on cystatin C, only over-diagnosed CKD stage 2 in 8.5%, 24.5% within 10% and 62.7% within 30%. We therefore combined both. The average Schwartz/Filler eGFR had 36.5% of results within 10%, 84.7% within 30%, and normal mGFR accuracy was 26.8%, 63.9% for 10% and 30%, respectively, outperforming the CKD-EPI and Pottel formulae. Conclusions: The Pierce U25 formula results correlated well with mGFR < 75 mL/min/1.73 m2. Over the entire GFR range, accuracy was better for patients with a higher mGFR, when averaging the combined Schwartz/Filler formulae. More work is needed to prospectively confirm our findings in other centers. [ABSTRACT FROM AUTHOR]

The article focuses on the need for validating estimated glomerular filtration rate (eGFR) formulae in diverse populations, particularly in underrepresented groups such as African children. Topics include the historical development of eGFR formulae, the limitations of existing approaches when applied to different demographics, and the importance of global collaboration to improve GFR estimation methods across various populations.

The article comments on a paper by Chloe Braun and colleagues on the estimation of glomerular filtration rate in pediatric and adult patients with acute kidney injury (AKI). Topics mentioned include the proposed formula for estimating baseline creatinine by age and sex, the link between serum creatinine and muscle mass, and the use of electronic health records with rule-based algorithms for immediate detection of AKI.

Aim: Review of current knowledge on assessing renal function in term and preterm neonates. Methods: Literature review and analysis of own data. Results: Prematurity, genetic, environmental and maternal factors may alter peak nephron endowment and life‐long renal function. Nephrogenesis continues until 34‐36 weeks of gestation, but it is altered with premature delivery. Variability of nephron endowment has a substantial impact on the clearance of renally excreted drugs. Postnatally, glomerular function rate (GFR) increases daily, doubles by two weeks, and slowly reaches full maturity at 18 months of age. Ideally, renal function biomarkers should be expressed as age‐independent z‐scores, and evidence suggests indexing these values to post‐conceptual age rather than chronological age. Newborn and maternal serum creatinine correlate tightly for more than 72 hours after delivery, rendering this biomarker unsuitable for the assessment of neonatal renal function. Cystatin C does not cross the placenta and may be the preferred biomarker in the neonate. Here, we provide preliminary data on the natural evolution of the cystatin C eGFR in infancy. Conclusion: Cystatin C may be superior for GFR estimation in neonates, but the best approach to drug dosing of renally excreted drugs remains to be established. [ABSTRACT FROM AUTHOR]

Background: Galloway-Mowat syndrome (GAMOS) (OMIM #251300) is a severe autosomal recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies caused by WDR73 as well as OSGEP, TP53RK, TPRKB, or LAGE3 mutations.Objective: We report on the hitherto undescribed urological and nephrological complications of the homozygous c.974G>A (p.Arg325Gln) OSGEP mutations in a 7-year-old Caucasian girl.Case diagnosis: The patient came to the attention of pediatric nephrology at the age of 3 years and 11 months, when she presented with status epilepticus due to profound hypomagnesemia (0.31 mmol/L, normal 0.65-1.05). A 24-h urine demonstrated a magnesium loss of 0.6 mmol/kg/day with associated proteinuria suggesting renal tubulopathy. Subsequently, she developed recurrent urinary tract infections (UTIs) and was diagnosed with neurogenic bladder dysfunction. The patient continued to have UTIs associated with seizures and sequential cultures growing multi-drug-resistant organisms despite of antibiotic prophylaxis. In addition, the proteinuria (median microalbumin/creatinine ratio 647 mg/mmol) increased, and she developed partial Fanconi syndrome. At age 7, she developed a large bladder calculus (3.3 × 3.2 cm) and three left non-obstructing renal calculi associated with elevated urinary cystine, hypercalciuria, and ongoing hypomagnesemia and required surgical intervention. Glomerular filtration rate (GFR) remained normal and she never developed frank nephrotic syndrome (average albumin 31 g/L).Conclusions: It is unclear if patients with OSGEP mutations with tubular symptoms rather than nephrotic syndrome should be considered a different entity. Nephrological and urological complications of OSGEP mutations can be challenging and require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Objectives Recent findings suggest that beta-trace protein (BTP), a small molecular weight protein, is at least equal if not superior to serum creatinine as a marker of glomerular filtration rate (GFR), particularly since it is independent from height, gender, age, and muscle mass. The authors sought to summarize knowledge on BTP and its use as a marker of GFR using the most recent literature available. Design and methods The authors compiled key articles and all relevant recent literature on this topic. Physical and chemical features of the molecule are described, as well as factors that may affect its expression. The use of BTP in estimating GFR as a whole and in specific patient groups, including pregnant women, neonates and infants, children and adolescents, and patients who have undergone renal transplantation is discussed. The use of BTP as a marker for cardiovascular risk factors is also briefly addressed. Results Although its performance in the general population is marginally inferior to cystatin C, studies have suggested that it may be superior in accurately estimating GFR in select patient groups such as pregnant women and neonates. Conclusions This novel marker shows promise, but further research is required to clarify findings from available data. [ABSTRACT FROM AUTHOR]

Serum creatinine does not share the properties of an ideal marker of glomerular filtration rate (GFR) like inulin, but continues to be the most widely used endogenous marker of GFR. In the search of a better biomarker of GFR, the small molecular weight protein cystatin C has been introduced with features more similar to that of inulin, such as constant production and no non-renal elimination. However, it has not enjoyed widespread use despite its significantly improved diagnostic performance in the detection of impaired GFR and its independence of body composition. A variety of formulae based on either cystatin C or creatinine or both have been developed to estimate GFR. We summarize the currently used methods of GFR measurement, their limitations and analytical errors. The review also summarizes the history, features and the feasibility of cystatin C measurements as well as the most widely used formulae for the estimation of GFR in children. The diagnostic performance of the cystatin C derived eGFR formulae at various levels of GFR is also discussed. An eGFR formula derived from pooled studies analyzing both creatinine and cystatin C, and using a biology-based mathematical approach may be advantageous. [ABSTRACT FROM AUTHOR]

Beta-trace protein (BTP) is a novel marker of glomerular filtration rate (GFR). To date, no pediatric formula for calculating GFR based on BTP has been developed. We measured GFR, serum creatinine and BTP in 387 children who underwent 474 99mTc-diethylene triamine pentaacetic acid renal scans. A BTP-based formula for estimating GFR was derived using stepwise linear regression analysis. A separate control group of 116 measurements in 99 children was used to validate the novel formula. A formula was also developed for each gender. The novel formula is: GFR = 10^(1.902 + (0.9515xLOG(1/BTP))). The Spearman rank correlation coefficient between the BTP-derived GFR estimate and the measured GFR was 0.80 [95% confidence interval (CI) 0.76–0.83], which is substantially better than that derived with the Schwartz formula ( r = 0.70, 95% CI 0.65–0.74). The Bland–Altman analysis revealed a mean bias of 1.21% [standard deviation (SD) 28%] in the formula development dataset, which was virtually identical to the 1.03% mean bias (29.5% SD) in the validation group and no different from the Schwartz formula bias. The percentage of values within 10% (33.0 vs. 28.3%) and 30% deviation (76.8 vs. 72.6%) were better for BTP-based formula than for the Schwartz formula. Separate formulas according to gender did not perform better than that for the pediatric population. This BTP-based formula was found to estimate GFR with reasonable precision and provided improved accuracy over the Schwartz GFR formula. [ABSTRACT FROM AUTHOR]

The aim is to review the tools for early detection of renal dysfunction after pediatric solid organ transplantation. Currently, the most widely used marker for detection of renal dysfunction involves measurement of GFR. Inulin clearance forms the “gold standard” method for measuring GFR; however, nuclear medicine methods (51Cr EDTA and 99Tc DTPA isotope clearance studies) have replaced inulin clearance. The measurement of serum creatinine has a low sensitivity for the early detection of renal damage. The Schwartz formula using patient height and serum creatinine requires center-specific constants and has limitations associated with creatinine determination. These limitations may be overcome using a cystatin C-based GFR estimation. In diabetic nephropathy, and more recently in hemolytic uremic syndrome, microalbuminuria has been established as a useful screening tool for renal damage, while its predictive value in the transplantation setting needs to be established. All transplant recipients should be screened for hypertension. Early referral for ambulatory 24-h blood pressure monitoring and involvement of pediatric nephrologists should be considered. All pediatric solid organ transplant recipients receiving CNI should be screened regularly for high blood pressure and early evidence of renal damage using either GFR scans or cystatin C-based GFR estimations. [ABSTRACT FROM AUTHOR]

The Cockcroft-Gault formula should not be used in children.Background.Although designed for adults, the Cockcroft-Gault formula was recently proposed for use in children≥13 years of age.Methods.We compared the feasibility of the Cockcroft-Gault formula against the standard pediatric Schwartz formula and a novel cystatin C–based formula. Our patient cohort included 262 children aged 1 to 18 years with various renal pathologies, who underwent a 99-technetium diethylenetriaminepentaacetate (99Tc DTPA) glomerular filtration rate (GFR) renal scan. Calculations were performed in Système International (SI) units using published constants and recalculated constants from our patient population. Agreement was assessed using Bland and Altman analysis.Results.Published and recalculated constants for the Cockcroft-Gault formula were 1.23 and 0.96, respectively, for boys, and 1.05 and 0.90, respectively, for girls. The published and recalculated constants for the Schwartz formula were 48 and 49.9, respectively, for boys≥13 years old, and 38 and 46.2, respectively, for all girls and for boys<13 years old. Using published constants, there was agreement between GFR and Cockcroft-Gault formula in boys≥13 years old (average bias 5.0± 23.5%) while there was an average error of−19.0%± 36.4% for all ages. Similarly, the average bias with Schwartz for boys≥13 years old was−6.8± 24.0% and for all patients was−12.8± 24.2%. Using recalculated constants, the average bias with Cockcroft-Gault in boys≥13 years old was−19.8± 23.5% and for all patients was−38.5± 35.2%. Similarly, the average bias with Schwartz for boys≤13 years old was−1.1± 24.3% and for all patients was 3.0± 24.0%. The novel cystatin C–based GFR calculations showed an average error of−4.9± 20.3% in the adolescent boys and 2.4± 20.4% for all ages.Conclusion.Cockcroft-Gault formula showed the worst agreement with GFR, regardless of using published or recalculated constants. The cystatin C–based approach resulted in the least error, and should be used for estimation of GFR. [ABSTRACT FROM AUTHOR]

To assess the validity of Cystatin-C (Cys-C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women.Prospective cross sectional study.Obstetric unit of a tertiary care hospital.One hundred and thirty-seven normal pregnant women and 13 women postpartum.Twenty-four hour creatinine clearance (CrCl), serum creatinine, Cys-C and BTP concentrations were measured on normal pregnant women in the first trimester (n= 5), second trimester (n= 68) and third trimester (n= 64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th centile).Serum concentrations of Cys-C and BTP compared with creatinine clearance and serum creatinine.The median serum creatinine throughout gestation was 53μmol/L (39, 71), and median CrCl was 143 mL/minute (91 to 216). Postpartum, creatinine rose to 74μmol/L (58, 86) and CrCl decreased to 104 mL/minute (71, 159). For Cys-C, the median concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP. Comparing the second and third trimesters, there was no significant difference between CrCl (median 145vs141 mL/minute) and BTP concentrations (median 0.51vs0.55 mg/L), while median Cys-C was significantly higher in the third trimester (0.61vs0.88 mg/L;P<0.001). Unlike creatinine and BTP, Cys-C levels decreased to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either of these markers to the standard used for GFR was between Cys-C and CrCl in the third trimester, and the correlation was weak (r= 0.27 for 1/Cys-CvsCrCl).These data demonstrate that despite claims to the contrary, Cys-C is a poor marker of GFR during pregnancy. Similarly, BTP shows little promise. [ABSTRACT FROM AUTHOR]

Abstract: Objective:: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). Methods:: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. Conclusions:: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular. [Copyright &y& Elsevier]

Editorial. Focuses on the evaluation of the use of cystatin C as a marker of glomerular filtration rate (GFR) over serum creatinine with the Schwartz formula in pediatric renal transplant patients. Comparison between cystatin C and GFR; Difference between the intercepts and elevation; Analysis of distinction between non-renal and renal transplant recipients.

Definitions of pediatric acute kidney injury (AKI) use changes of serum creatinine. There is a paucity of well-designed studies in infants because of creatinine age-dependency. The emerging role of cystatin C as a superior marker of renal dysfunction led to a carefully conducted study on AKI in infants by Zappitelli et al. This Commentary calls for the development of age-independent serum creatinine and estimated glomerular filtration rate z scores. [ABSTRACT FROM AUTHOR]

The management of pediatric patients with congenital heart disease and pediatric heart transplant recipients has become complex. One of the issues a pediatric cardiologist has to be mindful about is renal function, which is often impaired in these patients due to a variety of causes. There is consensus that glomerular filtration rate (GFR) is the best surrogate marker for renal function. Inulin clearance is the gold standard method for measurement of GFR, but it is invasive, cumbersome and requires bladder catheterization in smaller children. Nuclear medicine methods replaced the measurement of inulin clearance, but these methods are poorly standardized, not evaluated using appropriate two-compartmental models and have several drawbacks, including inaccuracy due to plasma protein binding or exposure to radiation. The most widely used endogenous marker of GFR, serum creatinine, is afflicted by multiple shortcomings, particularly in pediatric cardiology patients with congenital heart disease or cardiomyopathy. Creatinine is affected by dietary intake, nutritional status and muscle mass, which are often altered in these patients. Small molecular weight proteins such cystatin C may be the most promising endogenous alternatives. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the reference intervals for serum cystatin C (CysC) and beta-trace protein (BTP) as markers of renal function in preterm and term neonates. Design and Methods: Blood samples of 128 neonates (34% female) admitted to the NICU were analyzed to determine the levels of serum creatinine (enzymatically), CysC and BTP (nephelometric, Siemens Health Care). Results: The reference intervals, categorized by age, were reported for the 128 neonates. Median (lower/upper limit) BTP were 1.85 (0.57/3.16) and 1.27 (0.51/2.07) mg/L on days 1 and 3. In keeping with maturation of renal function after birth, CysC and BTP fell from days one to day three after birth, whereas creatinine did not. Conclusion: Our data provides reference intervals for the levels of creatinine, CysC, and BTP in neonates on days 1 and 3 after birth and demonstrates that CysC and BTP reflect neonatal renal function, whereas creatinine reflects maternal renal function. [Copyright &y& Elsevier]

The limitations of estimates of glomerular filtration rate (GFR) based only on serum creatinine measurements have spurred an interest in more sensitive markers of GFR. Beta-trace protein (BTP), a low-molecular-weight glycoprotein freely filtered through the glomerular basement membrane and with minimal non-renal elimination, may be such a marker. We have recently derived two GFR estimation equations based on BTP. To validate these equations, we measured BTP and the plasma clearance of 99mTc-DTPA in 92 adult kidney transplant recipients and 54 pediatric patients with impaired kidney function. GFR was estimated using the serum creatinine–based Modification of Diet in Renal Disease (MDRD) Study equation for adults, the Schwartz and updated Schwartz equations in children, and 4 novel BTP-derived equations (our 2 equations and 2 proposed by Poge). In adults, our BTP-based equations had low median bias and high accuracy such that 89–90% of estimates were within 30% of measured GFR. In children, the median bias of our 2 equations was low and accuracy was high such that 78–83% of estimates were within 30% of measured GFR. These results were an improvement compared to the MDRD and Schwartz equations, both of which had high median bias and reduced accuracy. The updated Schwartz equation also performed well. [ABSTRACT FROM AUTHOR]