Universal GFR determination based on two time points during plasma iohexol disappearance

Abstract

An optimal measurement of glomerular filtration rate (GFR) should minimize the number of blood draws, and reduce procedural invasiveness and the burden to study personnel and cost, without sacrificing accuracy. Equations have been proposed to calculate GFR from the slow compartment separately for adults and children. To develop a universal equation, we used 1347 GFR measurements from two diverse groups consisting of 527 men in the Multi center AIDS Cohort Study and 514 children in the Chronic Kidney Disease in Children cohort. Both studies used nearly identical two-compartment (fast and slow) protocols to measure GFR. To estimate the fast component from markers of body size and of the slow component, we used standard linear regression methods with the log-transformed fast area as the dependent variable. The fast area could be accurately estimated from body surface area by a simple parameter (6.4/body surface area) with no residual dependence on the slow area or other markers of body size. Our equation measures only the slow iohexol plasma disappearance curve with as few as two time points and was normalized to 1.73m2 body surface area. It is of the form: GFR=slowGFR/[1+0.12 (slowGFR/100)]. In a random sample utilizing a third of the patients for validation, there was excellent agreement between the calculated and measured GFR with low root mean square errors being 4.6 and 1.5ml/min per 1.73m2 for adults and children, respectively. Thus, our proposed simple equation, developed in a combined patient group with a broad range of GFRs, may be applied universally and is independent of the injected amount of iohexol.

Measurement and Estimation of Glomerular Filtration Rate in Children

“…GFR can then be derived from the slope of the slow curve but requires incorporation of a correction factor to compensate for overestimation of the GFR, which results from exclusion of the area under the fast curve. 12-16 Only 2 blood specimens are needed but must be timed appropriately; the first sample is obtained after the marker has equilibrated (~2 hours postinjection), whereas the second must be obtained at least 5 hours postinjection and potentially longer depending on the degree of CKD. The validity of this model may be compromised if the second sample is obtained too early as GFR can be overestimated from an inaccurate depiction of the lower slope of the plasma disappearance curve especially with low GFR.…”

Con: Should we abandon the use of the MDRD equation in favour of the CKD-EPI equation?

“…In the development data set, only urinary clearances of subcutaneously injected iothalamate were performed to measure GFR. In this measurement, precision is not the best [40] and, incidentally, the plasma clearance of iohexol has been shown to have a better precision and reproducibility [41][42][43]. Secondly, the relative lack of precision of the CKD-EPI equation is probably due to the studied population [7].…”

Estimating GFR in Adult Patients with Hematopoietic Cell Transplant

“…Blood samples were collected before iohexol infusion for hematocrit, serum Cr, iohexol blank, and CysC. GFR was measured by a twopoint iohexol plasma disappearance analysis using a onecompartment model approximation validated in both children and adults (19,20). After a time-zero blood sample was obtained, patients received a 5-ml intravenous injection of iohexol from a preweighed syringe (Omnipaque 300 GE Healthcare Amersham Division, Princeton, NJ).…”

“…In three participants, a finger-prick method was used to place blood on filter paper. GFR was computed from the iohexol dose divided by the area under the disappearance curve and scaled for body surface area of 1.73 m 2 (19,20). All blood samples were collected in serum separator tubes, inverted 5-10 times, and allowed to clot before being centrifuged at 3000 rpm (11873g) for 10 minutes.…”