Methods of assessing renal function

Department of Pediatrics, Children's Hospital, London Health Science Centre, University of Western Ontario, 800 Commissioners Road East, London, Ontario, Canada, N6A 5W9, .
Pediatric Nephrology (Impact Factor: 2.88). 02/2013; 29(2). DOI: 10.1007/s00467-013-2426-7
Source: PubMed

ABSTRACT 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.


Available from: Guido Filler, May 09, 2015
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sex may affect the performance of small molecular weight proteins as markers of GFR because of differences in fat mass between the two sexes. The hypothesis was that the diagnostic performance of β-trace protein, a novel marker of GFR, would be significantly better in boys than in girls. GFR, height, weight, serum creatinine, and β-trace protein were measured in 755 children and adolescents (331 girls) undergoing (99)technetium diethylenetriamine penta-acetic acid renal scans from July of 1999 to July of 2006. Boys and girls were separated into formula generation cohorts (284 boys and 220 girls) and formula validation cohorts (140 boys and 111 girls). GFR-estimating formulas on the basis of β-trace protein, creatinine, and height were derived using stepwise linear regression analysis of log-transformed data. The slope of the regression lines of the sex-specific eGFRs were compared. Bland-Altman analysis was used for testing agreement between (99)technetium diethylenetriamine penta-acetic acid GFR and calculated GFR both with this equation in boys and girls as well as previously established Benlamri, White, and Schwartz formulas. In the stepwise regression analysis, β-trace protein (R(2)=0.73 for boys and R(2)=0.65 for girls) was more important than creatinine (which increased R(2) to 0.81 for boys and R(2) to 0.75 for girls) and height (which increased R(2) to 0.88 for boys and R(2) to 0.80 for girls) in the data generation groups. GFR can be calculated using the following formulas:[Formula: see text]and[Formula: see text]Bland-Altman analysis showed better performance in boys than in girls. The new formulas performed significantly better than the previous Benlamri, White, and Schwartz formulas with respect to bias, precision, and accuracy. Improved and sex-specific formulas for the estimation of GFR in children on the basis of β-trace protein, serum creatinine, and height are now available. Copyright © 2014 by the American Society of Nephrology.
    Clinical Journal of the American Society of Nephrology 12/2014; DOI:10.2215/CJN.04860514 · 5.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose We assessed the reliability of calculating eGFR in children as compared to the iohexol disappearance test (GFR-I), which was performed 417 times in 353 children aged 2 and more. Material/methods eGFR was estimated with equations based on serum creatinine: Schwartz (1: eGFR-Scr), Cockroft–Gault (2: eGFR-CG) and MDRD (3: eGFR-MDRD), and on creatinine clearance (4: eGFR-U), or relying on serum cystatin C: Hoeck (5: eGFR-H), Bokenkamp (6: eGFR-B) and Filler (7: eGFR-F), and on the three Schwartz markers (8: eGFR-S3M). Mean relative error (RE), correlation (R), Bland–Altman analysis and accuracy of GFR-I were studied in all patients and in subgroups: at GFR < 60 ml/min/1.73 m2; in children aged ≤12 and >12. Results The results by eGFR-Scr, eGFR-S3M demonstrated no statistical difference to GFR-I at GFR < 60 ml/min/1.73 m2, but underestimated eGFR at higher filtration values by 11.6 ± 15.1% and 19.1 ± 16.4, respectively (p < 0.0000). The eGFR-B, eGFR-F and eGFR-MDRD equations illustrated important overestimation of reference GFR results (RE: 84 ± 44.2%; 29.5 ± 27.9%, 35.6 ± 62%; p < 0.0000 for all). The MDRD and C–G formulas showed statistically better consistency in children aged >12. A good agreement was achieved by the eGFR-H equation (5.1 ± 21.9%; p < 0.0000; R = 0.78). Conclusions (1) Schwartz equations show a good conformity at GFR < 60 ml/min/1.73 m2, but underestimate the results at higher GFR values. (2) The Bokenkamp equation with original coefficient should not be employed in children. (3) The use of the Hoeck formula in all children and C–G and MDRD formula in children aged >12 is possible. (4) The error of eGFR calculations increases at higher GFR values.
    Advances in Medical Sciences 08/2014; 60(1). DOI:10.1016/j.advms.2014.08.007 · 0.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To explore the potential of non-invasive reverse iontophoresis transdermal extraction of iohexol as a marker of glomerular filtration rate. Methods A series of in vitro experiments were undertaken to establish the feasibility of iohexol reverse iontophoresis and to determine the optimal conditions for the approach. Subsequently, a pilot study in paediatric patients was performed to provide proof-of-concept. Results The iontophoretic extraction fluxes of iohexol in vitro were proportional to the marker subdermal concentration and the reverse iontophoretic technique was able to track changes dynamically in simulated pharmacokinetic profiles. Reverse iontophoresis sampling was well tolerated by the four paediatric participants. The deduced values of the iohexol terminal elimination rate constant from transdermal reverse iontophoresis sampling agreed with those estimated by conventional blood sampling. Conclusions Reverse iontophoretic transdermal extraction fluxes mirrored the subdermal concentration profiles of iohexol, a relatively large neutral marker of glomerular filtration both in vitro and in vivo. The efficiency of extraction in vivo was well predicted by the in vitro model used.
    Pharmaceutical Research 09/2014; 32(2). DOI:10.1007/s11095-014-1488-y · 3.95 Impact Factor