Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease

Abstract

Measuring the glomerular filtration rate (GFR) by iohexol plasma disappearance in children requires optimization of duration and sampling times since shortening the study may overestimate GFR. To determine these parameters, we analyzed iohexol plasma disappearance curves using multiple sampling points in each of 27 children in the Chronic Kidney Disease in Children (CKiD) study. The GFR measured after 5 h was comparable to that after 6 h, but shortening to 4 h resulted in a significant 3% overestimation of GFR. We also sought to reduce the number of blood samples to determine GFR. This was done by adapting the Brochner-Mortensen equations to derive the relationship between a single-compartment two-sample (slow GFR model) disappearance curve and that from a double exponential analysis (two-compartment four-sample model) in the first clinic visit of 489 children. Using polynomial regression methods, we developed coefficients to accurately measure GFR from a single-compartment model. These coefficients were employed to recalculate the GFR and compare these to values measured with the two-compartment four-sample model in 361 of these children in their second clinic visit. There was excellent correlation (r=0.999) and no bias or change in between-individuals' dispersion. Hence, the GFR can be accurately measured in children with chronic kidney disease using the slow component of the iohexol plasma disappearance curve, provided the duration of study is at least 5 h.

1

Iohexol-based GFR as a function of time of sampling for the slow curve. GFR for each of the 27 studies of the pilot study was calculated after 4, 5, and 6 hours of sampling.

2

Relationship between GFRs based on the slow component only (x axis) and the four point GFR (double exponential, y axis) in 489 subjects at Visit 1 of the CKiD study. The regression equation for GFR is given near the bottom of the graph.

3

Comparison of GFR2 (based on the slow component using constants determined from Visit 1) to four-point GFR4 studies in Visit 2 (N= 362) of the CKiD study. Panel A, Percentile (2.5^th, 5^th, 10^th, 25^th, 50^th, 75^th, 90^th, 95th and 97.5^th) boxplots showing a high correlation (r= 0.999). Panel B, linear regression of GFR2 on GFR4 showing a very close agreement and a very high correlation.

3

Comparison of GFR2 (based on the slow component using constants determined from Visit 1) to four-point GFR4 studies in Visit 2 (N= 362) of the CKiD study. Panel A, Percentile (2.5^th, 5^th, 10^th, 25^th, 50^th, 75^th, 90^th, 95th and 97.5^th) boxplots showing a high correlation (r= 0.999). Panel B, linear regression of GFR2 on GFR4 showing a very close agreement and a very high correlation.

4

Bland-Altman analysis of GFR2 versus four-point GFR in the 362 subjects at Visit 2 of the CKiD study showing an insignificant bias of -0.002. The ratio of the SD of the GFR2 and the four-point GFR was essentially equal to 1.