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Published on: May 10, 2013
Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children
G J Schwartz1, S Furth, S R Cole
1Department of Pediatrics, University of Rochester School of Medicine, Golisano Children's Hospital at Strong, Rochester, New York 14642, USA. George_Schwartz@urmc.rochester.edu
Insights
Measuring glomerular filtration rate (GFR) in children using iohexol plasma disappearance is accurate with just four blood samples. This method is more reliable than estimated GFR or urinary clearance for pediatric chronic kidney disease studies.
Area of Science:
- Pediatric Nephrology
- Diagnostic Biomarkers
- Pharmacokinetics
Background:
- Accurate measurement of glomerular filtration rate (GFR) is crucial for diagnosing and managing chronic kidney disease (CKD) in children.
- Traditional GFR estimation methods in pediatric populations have limitations, necessitating validated alternative approaches.
Purpose of the Study:
- To evaluate the accuracy and reliability of using iohexol plasma disappearance curves for measuring GFR in children.
- To inform the design of a nationwide pediatric CKD cohort study by establishing an optimal GFR measurement protocol.
Main Methods:
- Iohexol was administered intravenously to 29 children, with serial blood samples collected over 360 minutes.
- High-performance liquid chromatography was used to assay iohexol concentrations.
- Glomerular filtration rate (GFR) was calculated using double exponential modeling of the plasma disappearance curve (GFR(9)) and compared with reduced data points (GFR(4), GFR(2)).
Main Results:
- GFR measurements using four plasma points (GFR(4)) showed excellent correlation (r=0.999) and no bias compared to nine-point measurements (GFR(9)).
- A two-point (GFR(2)) calculation also demonstrated strong correlation (r=0.986) with GFR(9).
- The Schwartz formula for estimated GFR overestimated actual GFR, while urinary iohexol clearance showed poor correlation due to collection variability.
Conclusions:
- Iohexol plasma disappearance curves provide an accurate and reliable method for measuring GFR in children.
- A four-point sampling strategy is sufficient for accurate GFR determination, with potential for even fewer points in some cases.
- This validated method supports its use in large-scale pediatric chronic kidney disease research.
Abstract:
To guide the design of a nation-wide cohort study of chronic kidney disease in children, we determined how iohexol plasma disappearance curves could be used in children to measure glomerular filtration rate (GFR). Iohexol (5 ml) was administered intravenously and blood samples were obtained at 10, 20, 30, 60, 120, 240, 300, and 360 min after injection (N=29) and assayed by high performance liquid chromatography. Four urines were also collected following the injection. Intra-assay coefficient of variation (CV) in serum was 1.3% at 100 mg/l, 2.6% at 15 mg/l, and 3.4% for duplicate unknowns. GFR(9) was computed from iohexol dose and area under the nine-point blood disappearance curve, using double exponential modeling. Only 2.8% of 254 data points deviated by >3 CV from the curves. GFR(4) calculated from 10, 30, 120, and 300 min points correlated well with GFR(9) (r=0.999) and showed no bias (means+/-s.d. of GFR(9) and GFR(4)=59.3+/-36.3 and 59.4+/-36.0 ml/min per 1.73 m(2)). Relationship of GFR(9) and one-compartment GFR followed quadratic equation as previously reported by Brochner-Mortensen, allowing GFR to be calculated from 120 and 300 min points. This GFR(2) correlated well with GFR(9) (r=0.986). Estimated GFR from Schwartz height/creatinine formula correlated with GFR(9)(r=0.934) but overestimated GFR by 12.2 ml/min per 1.73 m(2). Urine iohexol clearance was poorly correlated (r=0.770) with GFR(9) owing to variability in urine collections (median CV=24%). GFR can be measured accurately using four-point iohexol plasma disappearance (in most cases, two points suffice); estimated GFR and urinary clearances are less useful.
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