碘海醇血浆清除率测定法评估肾小球滤过率在慢性肾脏病中的临床应用

Clinical application of iohexol plasma clearance assay for determination of glomerular filtration rate in chronic kidney disease

目的探讨碘海醇血浆清除率测定法评估肾小球滤过率(glomerular filtration rate,GFR)在慢性肾脏病(chronic kidney disease,CKD)人群的临床应用价值,筛选临床上可替代同位素99m Tc‑二乙烯三胺五乙酸肾动态显像(Gates)法测定GFR(99m Tc‑mGFR)的较优方案。方法该研究为横断面研究。入选2022年10月至2023年9月在南京医科大学第二附属医院肾脏科住院的CKD患者为研究对象。碘海醇血浆清除率测定方法:分别在5 ml碘海醇静脉推注后2 h和4 h采血,采用高效液相色谱法检测血浆碘海醇浓度,并采用Bröchner‑Mortensen公式和Jacobsson公式计算双血浆及单血浆碘海醇清除率。血肌酐测定的估算肾小球滤过率(estimated glomerular filtration rate,eGFR)采用CKD流行病学协作公式计算。以99m Tc‑mGFR为金标准,应用Pearson相关分析法比较碘海醇双血浆清除率法测定的GFR(Iohexol‑DS‑mGFR)、碘海醇单血浆4 h清除率法测定的GFR(Iohexol‑SS4h‑mGFR)、碘海醇单血浆2 h清除率法测定的GFR(Iohexol‑SS2h‑mGFR)及eGFR与99m Tc‑mGFR的相关性;应用Bland‑Altman分析、95%一致性区间(95%limits of agreement,95%LoA)、组内相关系数等方法比较Iohexol‑DS‑mGFR、Iohexol‑SS4h‑mGFR、Iohexol‑SS2h‑mGFR及eGFR与99m Tc‑mGFR的诊断一致性。结果共计64例CKD患者入选该研究,年龄(58.91±13.08)岁,男性38例,女性26例。依据99m Tc‑mGFR分期,CKD 1期12例(18.8%),CKD 2期14例(21.9%),CKD 3期26例(40.6%),CKD 4期10例(15.6%),CKD 5期2例(3.1%)。Pearson相关分析结果显示,Iohexol‑DS‑mGFR、Iohexol‑SS4h‑mGFR、Iohexol‑SS2h‑mGFR及eGFR与99m Tc‑mGFR的相关系数分别为0.925、0.867、0.820、0.894(均P<0.001),在总研究人群中Iohexol‑DS‑mGFR、Iohexol‑SS4h‑mGFR、Iohexol‑SS2h‑mGFR和eGFR中位偏差绝对值分别为6.66、9.63、11.47和9.59 ml·min^(-1)·(1.73 m^(2))^(-1),P10(位于金标准GFR±10%区间的比例)分别为35.9%、29.7%、26.6%、29.7%,P30(位于金标准GFR±30%区间的比例)分别为87.5%、68.8%、60.9%、73.4%。结论碘海醇双血浆清除率与99m Tc‑mGFR具有较好的相关性和一致性,操作简便且安全,临床上可作为替代99m Tc‑mGFR的较优检测方案。

Objective To evaluate the clinical application value of iohexol plasma clearance assay in assessing glomerular filtration rate(GFR)in patients with chronic kidney disease(CKD),and identify alternative methods of 99mTc-diethylene triamine pentaacetic acid renal kinetic imaging(Gates)method for measuring GFR(99mTc‐mGFR).Methods It was a cross-sectional study.The CKD patients hospitalized in the Department of Nephrology at the Second Affiliated Hospital of Nanjing Medical University between October 2022 and September 2023 were enrolled.Iohexol plasma clearance was determined by collecting blood samples at 2 and 4 hours after intravenous administration of 5 ml iohexol,and high performance liquid chromatography was used to measure the plasma concentration of iohexol.Bröchner-Mortensen and Jacobsson formulas were used to calculate the double and single plasma iohexol clearance,respectively.CKD-epidemiology collaboration equation based on serum creatinine concentration was used to calculate the estimated GFR(eGFR).Pearson's coefficient was performed to analyze the correlation of iohexol dual plasma clearance assay-measured GFR(iohexol‐DS‐mGFR),iohexol single plasma 4 hours clearance assay-measured GFR(iohexol‐SS4h‐mGFR),iohexol single plasma 2 hours clearance assay-measured GFR(iohexol‐SS2h‐mGFR)and eGFR with 99mTc‐mGFR as the gold standard.Bland‐Altman analysis,95%limits of agreement,and intra-correlation coefficient were used to compare the diagnostic concordance of Iohexol‐DS‐mGFR,Iohexol‐SS4h‐mGFR,Iohexol‐SS2h‐mGFR and eGFR with 99mTc‐mGFR.Results The study enrolled 64 CKD patients,aged(58.91±13.08)years old,comprising of 38 males and 26 females.The distribution of patients across CKD stages based on 99Tc‐mGFR was as follows:12 patients(18.8%)in stage 1,14 patients(21.9%)in stage 2,26 patients(40.6%)in stage 3,10 patients(15.6%)in stage 4,and 2 patients(3.1%)in stage 5.The Pearson correlation analysis revealed that the correlation coefficients of iohexol‐DS‐mGFR,iohexol-SS4h‐mGFR,iohexol‐SS2h‐mGFR and eGFR with 99mTc‐mGFR were 0.925,0.867,0.820 and 0.894(all P<0.001),respectively.The median deviation of absolute value of iohexol‐DS‐mGFR,iohexol-SS4h‐mGFR,iohexol‐SS2h‐mGFR and eGFR in the total study population were 6.66,9.63,11.47 and 9.59 ml·min^(-1)·(1.73 m^(2))^(-1),respectively.The proportions of iohexol‐DS‐mGFR,iohexol-SS4h‐mGFR,iohexol‐SS2h‐mGFR and eGFR located in the gold-standard GFR±10%interval(P10)were 35.9%,29.7%,26.6%and 29.7%,respectively,and the proportions located in the gold-standard GFR±30%interval(P30)were 87.5%,68.8%,60.9%and 73.4%,respectively.Conclusions Iohexol dual plasma clearance is well correlated and consistent with 99mTc‐mGFR.It is a safe and easy alternative to isotope 99mTc‐mGFR for clinical use in determining GFR.