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

Abstract

Aims: Determination of systemic inulin clearance by the standard technique of constant intravenous infusion has long been accepted as a reliable method for measuring glomerular filtration rate (GFR) without urine collection, except in oedematous patients. However, recent studies using standard clearance techniques have claimed that systemic inulin clearance is significantly greater than renal clearance and therefore overestimates GFR. The main purpose of this investigation was to re-evaluate the relationship between systemic and renal inulin clearance using a different technical approach. A reassessment 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 the total area under the plasma concentration-time curve (AUC) following bolus intravenous injection. kenal clearance was calculated as the ratio of the total amount recovered in the urine to the AUC, and systemic clearance as dose/AUC.

Results: Inulin disposition kinetics were best described by a tri-exponential 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 volume; steady-state volume of distribution was 11.00 (1.21) 170 kg(-1), in accordance with the tenet that the inulin space is somewhat smaller than the extracellular fluid volume. The values of systemic and renal inulin clearances were very similar (96.1 (10.0) and 94.6 (12.5) ml min(-1) 70 kg(-1), respectively, in healthy subjects; 104.6 (16.3) and 102.6 (18.5) ml min(-1) in ascitic patients). They were also highly correlated to each other in both healthy subjects (r=0.96, P<0.001) and patients with ascites (r=0.98, P<O.001).

Conclusions: The method described here constitutes a simpler and more precise 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 short successive urine collections. By the present method we demonstrated that renal and systemic inulin clearances are virtually identical in both healthy subjects and patients with expanded extracellular fluid volume. Determination of systemic inulin clearance by the presently described technique is therefore a method of general validity for measuring GFR without urine collection.

Figure 1

Plasma decay curves of inulin in a healthy subject (•) and an ascitic patient (○). The solid lines are the curves obtained by nonlinear least-squares regression analysis of the data.