Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after (51)Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited.

SummaryBackground and objectives The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation.Design, setting, participants, & measurements We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium-99m-diethylene-triamine penta-acetic acid ( 99m Tc DTPA).Results We compared various cystatin C equations across GFR strata Ͻ60, Ͻ90, Ն135, and Ն150 ml/min per 1.73 m 2 for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective 99m Tc DTPA, in the GFR categories Ͻ60 and Ͻ90 ml/min per 1.73 m 2 , whereas the Bö kenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories Ն135 and Ն150 ml/min per 1.73 m 2 . The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR Ͻ60 and Ͻ90 ml/min per 1.73 m 2 , whereas the Bö kenkamp equation had a higher sensitivity for GFR Ն135 and Ն150 ml/min per 1.73 m 2 . ConclusionsThe diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations.

According to the Barker hypothesis, intrauterine growth restriction and premature delivery adversely affect cardiovascular health in adult life. The association of childhood hypertension as a cardiovascular risk factor and birth weight has been understudied. In a prospective cohort study, the authors evaluated the effect of birth weight, gestational age, maternal prepregnancy body mass index (BMI), and child BMI z score at the time of enrollment on the systolic and diastolic blood pressure (BP) z score in 3024 (1373 women) consecutive outpatient clinic patients aged 2.05 to 18.58 years. The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age‐dependent z scores. The median z scores of BMI (+0.48, range −6.96–6.64), systolic BP (+0.41, range −4.50–6.73), and diastolic BP (+0.34, range −3.15–+6.73) were all significantly greater than the NHANES III reference population. Systolic BP z score did not correlate with birth weight or gestational age, but did correlate with maternal prepregnancy BMI (r=.090, P<.0001) and BMI z score (r=.209, P<.0001). Diastolic BP z score positively correlated with birth weight (0.037, P=.044), gestational age (r=.052, P=.005), BMI z score(r=.106, P<.0001), and maternal prepregnancy BMI (r=.062, P=.0007). In contrast to what would be expected from the Barker hypothesis, the authors found no negative correlation between BP z score and birth weight or gestational age. This study suggests that a high BMI, a big mom, and a high birth weight are more important risk factors for hypertension during childhood than low birth weight or gestational age. J Clin Hypertens (Greenwich). 2011;13:35–41. ©2010 Wiley Periodicals, Inc.

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Summary 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.

In children, body mass exerts a minimal effect on the performance of CysC eGFR estimation.

Serum creatinine does not share the properties of an ideal marker of glomerular fi ltration 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 signifi cantly 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.

Background and objectives: Cystatin C, a low molecular weight protein, is produced by nucleated cells, filtered by glomeruli, and degraded by tubules at a constant rate. Its serum concentration has been proposed as a marker of GFR. Its size should make it dialyzable. It is hypothesized that serum cystatin C levels are influenced by the method and intensity of dialysis received.Design: This is a cross-sectional pilot study of cystatin C in functionally anephric dialysis patients. It was measured predialysis in 14 patients on conventional (3 to 5 h, 3 ؋ wk) hemodialysis; eight on nocturnal hemodialysis (three to seven nights, 6 to 8 h); three on daily hemodialysis (6 d, 1 1 ⁄2 to 2 1 ⁄2 h); and 10 on automated peritoneal dialysis. All had urea kinetic studies and values for single pool Kt/V (Sp Kt/V), standard weekly Kt/V (Std Kt/V), and protein equivalent of nitrogen appearance (nPNA; g/kg/d). C reactive protein (CRP; mg/L) and thyroid stimulating hormone (TSH; mIU/L) were measured as factors known to influence cystatin C.Results: There was no correlation between cystatin C and Sp Kt/V, but there was a significant inverse linear correlation with Std Kt/V and there were significant differences between treatment modalities in cystatin C levels and in Std Kt/V. The estimation of cystatin C was reliable and stable over 3 to 6 wk and its levels uninfluenced by nPNA, CRP, or TSH.Conclusion: Serum cystatin C levels are influenced by the method and intensity of dialysis and may have a role in treatment adequacy monitoring.