A practical method of measuring glomerular filtration rate by iohexol clearance using dried capillary blood spots.
BACKGROUND
Exogenous tracer-based methods of measuring glomerular filtration rate (GFR) are difficult to perform, whilst creatinine-based estimation formulae are inaccurate.


METHODS
We assessed a new technique of measuring iohexol clearance using timed dried capillary blood spots. A reference GFR was measured in 81 subjects (GFR 15-124 ml/min/1.73 m(2)) by iohexol clearance using three venous samples (2, 3 and 4 h after an intravenous bolus). GFR was estimated by six test methods; iohexol clearance using (i) 3 blood spots (2, 3, 4 h); (ii) 2 blood spots (2, 4 h) and (iii) 1 blood spot (4 h); (iv) the Modification of Diet in Renal Disease (MDRD) formula; (v) the Cockcroft-Gault formula, and (vi) a formula estimating GFR from serum cystatin C concentration. For each test method the bias and precision were calculated as the mean and standard deviation (SD) of the 'GFR differences' (test method GFR - reference GFR).


RESULTS
The limits of agreement (bias +/-1.96 x SD; in ml/min/1.73 m(2)) were: (i) 1.1 +/- 15.1 for 3-spot iohexol clearance; (ii) 0.6 +/- 14.9 for 2-spot iohexol clearance; (iii) 4.5 +/- 21.2 for 1-spot iohexol clearance; (iv) -15.7 +/- 33.3 for the MDRD formula; (v) -9.6 +/- 32.9 for the Cockcroft-Gault formula, and (vi) -12.1 +/- 31.7 for the Cystatin C formula. The accuracy of all six test methods was similar among individuals with GFR <60 ml/min/ 1.73 m(2); however, in individuals with GFR > or =60 ml/min/ 1.73 m(2), the MDRD, Cockcroft-Gault and Cystatin C formulae were all imprecise and systematically underestimated GFR.


CONCLUSIONS
Blood spot iohexol clearance provides a potentially practical method of estimating GFR accurately in large-scale epidemiological studies especially among individuals without established chronic kidney disease.
Mafham
Marion M
MM
Renal Studies Group, Clinical Trial Service Unit, Old Road Campus, Oxford, UK. mmafham@yahoo.co.uk
Niculescu-Duvaz
Ioana
I
Barron
Jeffrey
J
Emberson
Jonathan R
JR
Dockrell
Mark E C
ME
Landray
Martin J
MJ
Baigent
Colin
C
D000328:Adult; D002196:Capillaries; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007472:Iohexol / Q000493:pharmacokinetics*; D007674:Kidney Diseases / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012016:Reference Values; D012680:Sensitivity and Specificity
D007472:Iohexol; D003404:Creatinine