GADOLINIUM NEPHROTOXICITY: A MEASUREMENT OF GLOMERULAR FILTRATION RATE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 肾毒性的评价通常通过给予造影剂（CM）后48至72小时获得的血清肌酐水平进行-从肾损伤到血清肌酐测量值改变的临床滞后。血清肌酐升高0.5 mg%或25%是CIN的标准定义。当通过测量的肾小球滤过率（GFR）评估肾功能时，尚未建立标准。 很少有人知道注射后不久GFR的变化。 常见的模拟GFR评估，肌酐清除率，取决于Cockcroft和Gault以及MDRD（血清肌酐和修饰物）等公式。 该估计具有可疑的临床价值，因为它依赖于已知滞后48至72小时的血清肌酐测定。 碘化造影剂是一种纯肾小球滤液（由肾小球过滤，既不被肾小管排泄也不被肾小管重吸收）。小剂量（<50 ml）碘化CM对肾功能无影响（肾毒性通常被认为是剂量依赖性的）。 利用RENIGERZER PRX 90仪器定量非同位素碘的血浆水平（即，使用含有不透射线CM的碘的浓度），可以从单个血浆样本中确定GFR。与常规放射性核素51 Cr-EDTA相比，RENZER单样品技术的可靠性更高。 本研究的目的是测量肾功能正常（血清肌酐<1.4 mg/ml）患者的“真实的”GFR，这些患者将接受钆给药以进行临床指征MRI。 将招募需要钆CM增强MRI研究的成人患者（>18岁）。 患者将同意接受钆CM增强MRI研究。 在MRI成像研究之前，将使用30 ml（300 mg/ml）碘不透射线造影剂进行GFR测定，并抽血。 患者将按照成像方案注射钆CM进行MRI研究，并抽血。 将通过RENDEZER GFR测定分析GFR，其基于CM中碘的血浆衰减。3小时后（考虑到血管外/血管内偏移的平衡），使用多点图进行的初步研究表明GFR测定与x轴（时间）一致，结果为直线图。随后将该多点分析修改为碘化CM注射后3小时的单一样品。将在RENDERZER中分批分析血浆样本。 如果GFR测定值在3小时内与基线研究相比保持不变，则确认钆CM对肾功能无影响。 但是，如果GFR降低（>25%），则表示造影剂诱导的肾毒性。选择该百分比变化是为了符合诊断不透射线造影剂肾毒性的公认血清肌酐升高25%。 初步实验表明，钆不会干扰碘的Renalyzer测定，因此证明使用碘化造影剂来确定患者的GFR是合理的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The evaluation of nephrotoxicity has classically been performed by serum creatinine levels obtained 48 to 72 hours after administration of contrast media (CM) - the clinical lag from the renal insult to an altered serum creatinine measure. A 0.5 mg% or a 25% increase of serum creatinine is the standard definition of CIN. No criteria has been established when renal function is assessed by measured glomerular filtration rate (GFR). Little is known of GFR alterations in time shortly after injection. The common simulated GFR evaluation, creatinine clearance, is dependent upon formulas such as Cockcroft and Gault and MDRD (serum creatinine and modifiers). This estimation has a questionable clinical value, since it is dependent upon serum creatinine assays that are known to lag by 48 to 72 hours. Iodinated contrast media is a pure glomerular filtrate (filtered by the glomerulus and is neither excreted nor reabsorbed by the tubules). In small doses (<50 ml) the iodinated CM has no documented impact upon renal function (nephrotoxicity is usually considered to be dose dependent). Utilizing the RENALYZER PRX90 instrument to quantify plasma levels of non isotopic iodine (i.e., concentration of the administered iodine containing radio-opaque CM), GFR can be determined from a single plasma sample. Reliability of the RENALYZER single sample technique has compared favorably with the usual radionuclide 51Cr-EDTA. The goal of this investigation is to measure "real" GFR in patients with normal renal function (serum creatinine <1.4 mg/ml) who will have gadolinium administered for a clinically indicated MRI. Adult patients (>18 years) in need of gadolinium CM-enhanced MRI study will be recruited. The patients will be consented for the MRI study with gadolinium CM enhancement. Prior to the MRI imaging study, GFR determination will be performed utilizing a 30 ml (300 mg/ml) iodine radio-opaque contrast agent, and blood will be drawn. The patients will have their MRI study with the injection of gadolinium CM as per imaging protocol, and blood will be drawn. GFR will be analyzed by RENALYZER GFR determination, which is based upon the plasma attenuation of the iodine in the CM. After three hours (allowing for an equilibrium of extra vascular/intravascular shift), initial investigation with a multi plot graph demonstrated GFR determinations consistent with the x axis (time) and results in a straight line graph. This multiple plot assay subsequently was modified to a singe sample 3 hours after iodinated CM injection. The plasma samples will be analyzed in the RENALYZER in batches. If the GFR determination remains unchanged from the baseline study over the 3 hours, there is a confirmation of no effect of the gadolinium CM upon renal function. However, if there is a decrease in GFR (>25%), this will represent contrast-induced nephrotoxicity. This percentage change was chosen to comply with the accepted 25% increase in serum creatinine for the diagnosis of nephrotoxicity of radio-opaque contrast media. Initial experimentation has shown that gadolinium does not interfere with the Renalyzer assay of iodine, thus justifying the use of an iodinated contrast agent to establish the patient's GFR.