GLOMERULAR-FILTRATION RATE MEASUREMENTS IN CLINICAL-TRIALS

To assess the utility and precision of GFR measurements in multicenter trials, the test performance and variability of GFR were analyzed in 2,250 patients enrolled in 44 clinical centers participating in either the Modification of Diet in Renal Disease (MDRD) Study or the Diabete s Control and Complications Trial (DCCT). GFR was measured as the rena l clearance of (I-125)iothalamate after an sc injection without epinep hrine. The studies used similar protocols for obtaining blood and urin e, training clinical center staff, and processing specimens in central laboratories. The performance of GFR measurements, assessed from adhe rence to protocol and quality control analyses, was excellent. The var iability among the four clearance periods (intratest coefficient of va riation (CV)) was acceptable; the median intratest CV for GFR was 9.4% in the MDRD Study and 11.7% in the DCCT. The pattern of decline in se rum counts was better approximated by an exponential rather than a lin ear relationship. The cause of the intratest variability in GFR measur ements was explored by univariate and multivariate analysis. The intra test CV was highest at the extremes of GFR. Among patients with a high GFR (>90 mL/min per 1.73 m2), most of whom were participants in the D CCT, the higher intratest GFR was due, in part, to a systematic declin e in GFR during the test. Among patients with a very low GFR (<13 mL/m in per 1.73 m2), technical difficulties in urine collections contribut ed substantially to the higher intratest CV. Other patient characteris tics, including age, gender, weight, serum glucose, renal diagnosis, a nd use of diuretics, were not strongly correlated with the intratest C V. The precision of GFR measurements was assessed from the variability from measurement to measurement (intertest CV). Among MDRD Study subj ects, in whom two measurements of GFR were performed over a 3-month in terval, the median intertest CV was relatively low (6.3%) and was only weakly related to the intratest CV. Thus, GFR measurements are reason ably precise, even if the intratest CV is high. Given the relatively h igh intratest CV that is characteristic of GFR measurements, the estim ate of GFR in an individual is more precise if multiple clearance peri ods, rather than a single period, are included. Similarly, the estimat e of mean GFR for a population is also more precise if multiple cleara nce periods are included. In conclusion, by the use of standardized me thods, an acceptable precision of GFR results can be obtained in multi center trials. The same methods can be applied in clinical practice. T he usefulness of GFR measurements in practice depends, in part, on the results of these and other ongoing clinical trials investigating ther apeutic interventions to prevent the onset or retard the progression o f renal disease.