Dejaco Alexander, Dorn Christoph, Paal Michael, Gruber Michael, Graf Bernhard M, Kees Martin G
Department of Anesthesia, University Hospital Regensburg, Regensburg, Germany.
Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
Front Pharmacol. 2024 Feb 1;15:1346343. doi: 10.3389/fphar.2024.1346343. eCollection 2024.
Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by high-performance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (-3.44 mL/min/1.73 m) compared to estimations based on creatinine alone (-0.76 mL/min/1.73 m), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73 m) and higher Lin's correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies.
准确评估肾功能具有重大的临床和科学意义,因为它是关键药物重要的药代动力学协变量。碘海醇清除率与肾小球滤过率几乎相同,但其测定通常需要静脉注射,因此存在内在风险。这促使我们展示一种利用真实世界数据在常规护理之外无需额外风险或采血来量化肾功能的方法。我们招募了37名接受高剂量碘海醇进行计算机断层扫描成像的重症监护患者,并通过高效液相色谱法(HPLC-UV)对一系列碘海醇血浆浓度进行了量化。通过对数线性回归和非线性最小二乘法拟合得出碘海醇清除率,并与通过CKD-EPI-2021公式估算的肾小球滤过率进行比较。非线性拟合不仅结果更准确,而且在处理时间不规则的数据点时更稳健。与仅基于肌酐的估计值(-0.76 mL/min/1.73 m²)相比,碘海醇清除率与基于肌酐和胱抑素C的估计值的一致性显示出略高的偏差(-3.44 mL/min/1.73 m²),但一致性界限明显更窄(±42.8 vs. 56 mL/min/1.73 m²)且林氏相关性更高(0.84 vs. 0.72)。总之,我们已经证明了碘海醇方法在重症监护医学中的可行性和性能,并描述了其在临床实践和药理研究中的应用工作方案。