Is 125I iothalamate an ideal marker for glomerular filtration?

Abstract

The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37°C; a difference that was abolished at 0°C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (C(IOT)) was twice (P < 0.05) that of EDTA (C(EDTA)) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. C(EDTA) was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P < 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEF(IOT) was significantly reduced (P < 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P < 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P < 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P < 0.005) and 22% (unchanged) for PAH and EDTA, respectively. In six healthy volunteers the renal clearance of unlabelled IOT (HPLC method) equated that of creatinine but exceeded that of inulin with 38% (P < 0.01). This difference was reduced 34% (P < 0.05) by probenecid (1 g i.v.). In nineteen patients with a single or two kidneys the average plasma clearance (single injection technique; slope-intercept method) of IOT was 13% higher than that of EDTA (P < 0.001); a difference which was significantly (P < 0.01) reduced to half after pretreatment with probenecid (1 g i.v.); in some patients this difference was marked. The results show that IOT is subject to a significant and in some cases marked renal tubular secretion in chicken, rats, and humans. IOT therefore, is not an ideal marker for glomerular filtration.