title: Extracellular distribution volumes of hydrophilic solutes used to measure the glomerular filtration rate: comparison between chromium-51-EDTA and iohexol.
abstract: Extracellular fluid volume (ECV) is larger when measured with Tc-99m-DTPA ( approximately 500 Da) than inulin (6 kDa). As part of an assessment of the suitability of the non-radioactive marker, iohexol, against the gold standard tracer, Cr-51-EDTA, for measurement of the glomerular filtration rate (GFR) based on a postal service, we took the opportunity to determine if this volume dependence is present for diffusible markers less disparate in size than inulin and Tc-99m-DTPA. Cr-51-EDTA ( approximately 400 Da) and iohexol ( approximately 900 Da) were administered into the opposite arms of 20 normal volunteers (fasting and non-fasting) and 60 patients (non-fasting), including 36 diabetics, 10 cancer patients and 13 dermatology patients. Blood was obtained from both arms 20, 40, 60, 120, 180 and 240 min after injection and assayed for a marker injected contra-laterally. The glomerular filtration rate (GFR) and mean indicator transit time, T, were measured from the bi-exponential clearance curves. ECV, the product of GFR and T, was subdivided into V(1) (administered indicator divided by the sum of zero-time intercepts of the two exponentials) and V(2) (the difference between V(1) and ECV). Variables were scaled to 1.73 m(2). For all 100 studies, the mean GFR from Cr-51-EDTA was 3 ml min(-1) higher than iohexol (p < 0.01). ECV was 0.41 L higher (p < 0.02) and V(1) 0.65 L higher (p < 0.001) from Cr-51-EDTA but V(2) was 0.33 L lower (p < 0.02). V(1)/ECV was 0.031 higher from Cr-51-EDTA (p < 0.01). ECV and V(2) from Cr-51-EDTA were both higher in diabetics (15.1 [1.7] and 5.0 [0.095] L, respectively) compared with normal non-fasting subjects (13.7 [1.5] and 4.3 [1.0]; p < 0.01). ECV and the volumes of its sub-compartments are different between markers that are less than an order of magnitude different in size.
authors.affiliation: Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bird
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: A Robert
authors.initials: AR
authors.lastname: Michell
authors.forename: A Michael
authors.initials: AM
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D003287:Contrast Media; D003627:Data Interpretation, Statistical; D003920:Diabetes Mellitus / Q000503:physiopathology; D004435:Eating / Q000502:physiology; D004492:Edetic Acid; D045604:Extracellular Fluid / Q000502:physiology*; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007472:Iohexol; D007674:Kidney Diseases / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology; D012016:Reference Values; D015203:Reproducibility of Results; D012871:Skin Diseases / Q000503:physiopathology
chemical_list: D003287:Contrast Media; D007472:Iohexol; D004492:Edetic Acid