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Feasibility and Impact of the Measurement of Extracellular Fluid Volume Simultaneous with GFR by ¹²⁵I-Iothalamate

Folkert W. Visser^*, Jaap H. J. Muntinga, Rudi A. Dierckx, and Gerjan Navis^*

Departments of ^* Nephrology and Nuclear Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; and Department of Medical Physiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands

Correspondence: Dr. Folkert W. Visser, University Medical Center Groningen, Department of Internal Medicine, Division of Nephrology, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Phone: 31-50-3612277; Fax: 31-50-3619310; E-mail: f.visser{at}int.umcg.nl

The feasibility, validity, and possible applications of the assessment of extracellular fluid volume (ECFV) simultaneous with glomerular filtration rate (GFR) were assessed in a series of validation studies using the constant infusion method of ¹²⁵I-iothalamate (IOT). In 48 subjects with a broad range of GFR, distribution volume (V_d) of IOT corresponded well with V_d bromide (16.71 ± 3.0 and 16.73 ± 3.2 l, respectively, not significant), with a strong correlation (r = 0.933, P < 0.01) and without systematic deviations. Reproducibility assessment in 25 healthy male subjects showed coefficients of variation of 8.6% of duplicate measurement of V_d IOT during strictly standardized (50 mmol Na⁺/d) sodium intake. An increase in dietary sodium intake (200 mmol Na⁺/d) induced a corresponding rise in V_d IOT of 1.11 ± 1.5 l (P < 0.01). In 158 healthy prospective kidney donors, the impact of indexing of GFR to ECFV was analyzed. Age, gender, height, and body surface area (BSA) were determinants of GFR. Whereas GFR, GFR/BSA, and GFR/height were gender-dependent, GFR/ECFV was gender-independent and not related to height or BSA. This supports the potential of normalizing GFR by ECFV. Thus, ECFV can be simultaneously assessed with GFR by the constant infusion method using IOT. After appropriate validation, also other GFR tracers could be used for such a simultaneous estimation, providing a valuable resource of data on ECFV in renal studies and, moreover, allowing GFR to be indexed to the body fluid compartment it clears: the ECFV.