Mohamed Abdulfataah A A, Gansevoort Ron T, van de Merbel Nico C, van Londen Marco, de Borst Martin H, Zijlma Rolf, Junier Lenneke A T, Heerspink Hiddo J L, Stevens Jasper
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Clin Kidney J. 2025 Sep 23;18(10):sfaf293. doi: 10.1093/ckj/sfaf293. eCollection 2025 Oct.
Kidney function can be assessed by the measured glomerular filtration rate (mGFR) and effective renal plasma flow (ERPF) using the exogenous filtration markers I-iothalamate and I-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% (P) and ≥50% within ±10% (P). 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 P of 100% and a P 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 I-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.
肾功能可通过使用外源性滤过标记物碘肽酸钠和碘马尿酸来测量肾小球滤过率（mGFR）和有效肾血浆流量（ERPF）进行评估。由于对患者、工作人员和环境存在放射性负担，这些标记物并不理想。我们研究了是否能用其非放射性同位素类似物的测量（“冷法”）替代这些放射性标记化合物的测量（“热法”）。
我们采用热法（γ计数法）和冷法（液相色谱 - 串联质谱法）对220名参与者的同一血清、尿液和输液溶液样本测定mGFR和ERPF。使用Passing - Bablok回归和Bland - Altman分析评估两种方法之间的一致性。准确性标准为热法和冷法测量的mGFR中≥80%在±30%（P）范围内，≥50%在±10%（P）范围内。通过偏差的标准差（SD）评估mGFR的精密度，并确定测量方法的批内变异系数（CV%）。
比较热法和冷法时，mGFR测量的平均差异为1.97%，且无临床相关偏差。mGFR的P值为100%，P值为76%，测量准确。冷法精密度良好；标准差为8.04 ml/min，批内CV%为3.01±3.15%。ERPF值的平均差异为19.2%，存在较大的恒定和比例偏差。在碘马尿酸制剂中发现了影响热法的放射化学杂质，这是两种方法存在差异的原因。
与热法相比，冷法提供了等效的mGFR结果。使用冷法测定的ERPF不受显著影响热法的放射化学杂质的影响。
