Effect of extracellular fluid volume on single-sample measurement of glomerular filtration rate

Objective. The objective of our study was to evaluate the effect of extracellular fluid volume (ECV) on the accuracy of measurement of glomerular filtration rate from a single sample (GFR1).

Multi-sample GFR (GFR6) and ECV (per 1.73 m(2)) were measured with both Cr-51-EDTA and iohexol, injected into opposite arms (110 studies in 80 subjects). Six plasma samples were obtained bilaterally 20- 240 min post-injection to measure GFR6/1.73 m(2). GFR1/1.73 m(2) was calculated from 2-, 3- and 4-h samples using Jacobsson's formula for iohexol and the Christensen and Groth formula for Cr-51-EDTA. The quotient, GFR1/GFR6, was taken to indicate the accuracy of GFR1.

When GFR6 was <60 ml/min/1.73 m(2), GFR1/ GFR6 correlated positively with ECV at all single-sample times. When GFR6 was 60-90 ml/min/1.73 m(2) or >90 ml/min/1.73 m(2), GFR1/GFR6 correlated positively with ECV at 2 h, but negatively at 4 h, indicating that at some time between 2 and 4 h, GFR1/GFR6 was transiently independent of ECV. A plot of the regression gradient of GFR1/GFR6 on ECV against sample time indicated that the time of transient independence, at which time GFR1 depends exclusively on GFR6, was 3.2-3.9 h (depending on indicator combination used) when GFR6 was 60-90 ml/min/1.73 m(2) and 2.4-2.9 h when GFR was >90 ml/min/1.73 m(2). Transient independence when GFR6 was <60 ml/min/1.73 m(2) was not reached by 4 h and estimated to be 5-7 h.

The accuracy of GFR1 depends on ECV, overestimation or underestimation respectively depending on sample time and GFR. The time at which GFR1 is independent of ECV increases with decreasing GFR. If sampling time is too early, GFR1 overestimates GFR, but the reverse occurs when sampling is too late, even if GFR is abnormally low.