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

## TL;DR

This study compares radioactive and non-radioactive methods for measuring kidney function and finds that the non-radioactive method gives equally accurate results for one key measure.

## Contribution

The study demonstrates that non-radioactive isotopologues can replace radiolabelled compounds for measuring glomerular filtration rate without clinically relevant bias.

## Key findings

- Non-radioactive mGFR measurements showed 100% accuracy within ±30% and 76% within ±10% compared to radioactive methods.
- Radiochemical impurities in the radioactive method caused significant bias in ERPF measurements.
- The non-radioactive method had a precision of 3.01% intratest coefficient of variation.

## Abstract

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.

GRAPHICAL ABSTRACT