Determination of inulin clearance by bolus intravenous injection in healthy subjects and ascitic patients: equivalence of systemic and renal clearances as glomerular filtration markers

Aims Determination of systemic inulin clearance by the standard technique o f constant intravenous infusion has long been accepted as a reliable method for measuring glomerular filtration rate (GFR) without urine collection, e xcept in oedematous patients. However, recent studies using standard cleara nce techniques have claimed that systemic inulin clearance is significantly greater than renal clearance and therefore overestimates GFR. The main pur pose of this investigation was to re-evaluate the relationship between syst emic and renal inulin clearance using a different technical approach. A rea ssessment was also made of inulin disposition kinetics. Methods Systemic and renal inulin clearances were simultaneously evaluated, in healthy subjects and patients with oedema and ascites, by analysis of t he total area under the plasma concentration-time curve (AUC) following bol us intravenous injection. Renal clearance was calculated as the ratio of th e total amount recovered in the urine to the AUG, and systemic clearance as dose/AUG. Results Inulin disposition kinetics were best described by a tri-exponentia l model. In healthy subjects the volume of the central compartment (mean (s .d.) value 3.86 (1.00) 70 kg(-1)) was slightly greater than the plasma volu me; steady-state volume of distribution was 11.00 (1.21) 170 kg(-1) in acco rdance with the tenet that the inulin space is somewhat smaller than the ex tracellular fluid volume. The values of systemic and renal inulin clearance s were very similar (96.1 (10.0) and 94.6 -1 70 kg(-1), respectively, in he althy subjects; 104.6 (16.3) and 102.6 (12.5) mi min(-1) in ascitic patient s). They were also highly correlated to each other (18.5) mi min(-1) in bot h healthy subjects (r=0.96, P<0.001) and patients with ascites (r=0.98, P<0 .001). Conclusions The method described here constitutes a simpler and more precis e technique for measuring renal inulin clearance than the standard method, which is based on constant infusion and timed collections of urine samples, since it avoids errors connected with shea successive urine collections. B y the present method we demonstrated that renal and systemic inulin clearan ces are virtually identical in both healthy subjects and patients with expa nded extracellular fluid volume. Determination of systemic inulin clearance by the presently described technique is therefore a method of general vali dity for measuring GFR without urine collection.