Iothalamate clearance and its use in large-scale clinical trials.

Several recently completed or ongoing large-scale clinical trials, including the Modification of Diet in Renal Disease Study, the Diabetes Control and Complications Trial, and the African-American Study of Kidney Disease and Hypertension, have all chosen the renal clearance of sodium 125I-iothalmate to monitor renal disease progression. The need for accurate and precise renal testing at multiple clinical sites, with centralized renal sample processing, clearly exceeds the limited scope of most other glomerular filtration rate methods. Analysis of 3580 studies combined from the Modification of Diet in Renal Disease Study and Diabetes Control and Complications Trial demonstrates that trained clinical personnel can successfully perform the 125I-iothalamate clearance glomerular filtration rate method in large-scale studies. Overall, intratest and interest glomerular filtration rate coefficients of variation of approximately 10 and 6% are acceptable for such studies. Strict standardization of glomerular filtration rate protocol with respect to water loading, equilibration time after injection, and pre-study fasting is of crucial importance. Other confounding phenomena, including regression to the mean of progression slopes, must be considered before renal results of an intervention can be assessed. The 125I-iothalamate clearance glomerular filtration rate method offers good accuracy and precision, reasonable clinical convenience, straightforward and efficient central laboratory analysis, and reasonable cost and safety for large-scale clinical trials.