Rationale & Objective

Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single- and multiple-sample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts.

Study Design

Cross-sectional investigation.

Setting & Participants

Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n = 805), the Berlin Initiative Study (BIS, n = 570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n = 1,324).

Tests Compared

High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single- versus multiple-sample protocols.

Outcomes

Measures of agreement between methods.

Results

Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin’s concordance correlation coefficient ρ was >0.96 and C_b (accuracy) was >0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were −0.25 and −0.15 mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively.

Limitations

Lack of comparison with an independent gold-standard method.

Conclusions

Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies.

中文翻译：

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跨人群的血浆碘海醇清除率的可比性。

理由与目标

尽管有几个重要且众所周知的局限性，但基于肌酐或半胱氨酸蛋白酶抑制剂C水平的肾小球滤过率（GFR）估算是目前流行病学研究和临床试验中评估GFR的标准方法。血浆碘海醇清除率已被提议作为一种廉价的GFR测量方法，可以在许多研究项目中替代估计的GFR。但是，碘海醇试验缺乏标准化，以及使用不同的方案（例如单样品和多样品方法）可能会妨碍跨研究的比较。我们在3个以人口为基础的欧洲人群中比较了iohexol测定法和GFR测量方案。

学习规划

横断面调查。

设置与参与者

年龄，基因/环境易感性-肾脏研究（AGES-Kidney； n = 805），柏林倡议研究（BIS，n = 570）和肾脏碘海醇清除率调查随访研究（RENIS-FU; n）的参与者= 1,324）。

测试比较

碘海醇的高效液相色谱分析。血浆碘海醇的清除率是使用单样品方案或多样品方案计算得出的。

结果

方法之间的一致性度量。

结果

从这三项研究中获得冷冻样品，并在北挪威大学医院的实验室中重新测量了碘海醇的浓度。Lin的一致性相关系数ρ> 0.96，C _b在所有3个队列中，重新测量的血清iohexol浓度相对于原始血清iohexol的（准确性）均大于0.99，并且Pass-Bablok回归未发现测量之间的差异，但对数转换的斜率是1.025（95％CI，1.006-1.046） AGES-肾脏测量。将AGES-Kidney和BIS中的多样品碘海醇清除率测量值与源自相同碘海醇测量值的单样品GFR进行了比较。AGES-Kidney和BIS中多样品相对于单样品GFR的平均偏差为-0.25和-0.15 mL / min，绝对差异的99％和97％分别在多样品结果的10％以内。

局限性

缺乏与独立金标准方法的比较。

结论

在3个研究队列中，碘海醇试验与清除方案之间的一致性是重要的。我们的发现表明，在这些研究中可以比较血浆碘海醇的清除率。