Comparison of radioactive and non-radioactive iothalamate and hippuran to assess kidney function

Kidney function can be assessed by the measured glomerular filtration rate (mGFR) and effective renal plasma flow (ERPF) using the exogenous filtration markers ¹²⁵I-iothalamate and ¹³¹I-hippuran. These markers are unfavourable due to the radioactive burden for patients, personnel and the environment. We studied whether we could replace the measurement of these radiolabelled compounds ('warm method') with the measurement of their non-radioactive isotopologues ('cold method').

We determined mGFR and ERPF in 220 participants by both the warm (gamma counting) and cold (liquid chromatography-tandem mass spectrometry) methods on the same serum, urine and infusion solution samples. Agreement between the methods was evaluated using Passing-Bablok regression and Bland-Altman analysis. Accuracy criteria were that ≥80% of the warm and cold mGFR measurements were within ±30% (P₃₀) and ≥50% within ±10% (P₁₀). Precision of mGFR was assessed by the standard deviation (SD) of the bias and the intratest coefficient of variation (CV%) of the measurement methods were determined.

mGFR measurements showed a mean difference of 1.97% and no clinically relevant bias when comparing the warm and cold methods. mGFR was accurate with a P₃₀ of 100% and a P₁₀ of 76%. The cold method was precise; the SD was 8.04 ml/min and the intratest CV% was 3.01 ± 3.15%. The ERPF values showed a mean difference of 19.2% and a large constant and proportional bias. Radiochemical impurities, which influence the warm method, were found in the ¹³¹I-hippuran formulation, and these were the cause of the discrepancy between the two methods.

The cold method provides equivalent mGFR results compared with the warm method. The ERPF determined using the cold method is unaffected by radiochemical impurities that significantly affect the warm method.