Ideal Marker Of Glomerular Filtration Rate Research Articles

3-Aminophenylboronic acid-mediated aggregation of gold nanoparticles for colorimetric sensing of iohexol in environmental and biological samples

Iohexol (IHO), as one of iodinated X-ray contrast, is often used as not only a chemical marker for tracking wastewater contamination in aquatic environment, but also an ideal glomerular filtration rate marker for explorating kidney disease. To these aims, it is important to establish reliable, fast, and cheap methods to detect IHO in environmental and biological samples. This work describes for the first time the development of a selective, sensitive and reliable colorimetric sensing assay for the fast determination of IHO in environmental and biological samples based on 3-aminophenylboronic acid (3-APBA) mediated aggregation of gold nanoparticles (AuNPs). In this approach, 3-APBA can assemble on the AuNPs surface through electrostatic interaction between its amino groups with the negatively charged citrate stabilizer of AuNPs to form AuNP@3-APBA. Subsequently, the aggregation and visual color change of the assembled AuNP@3-APBA are induced by the covalent reaction between boronic acid ligands of 3-APBA and cis-diols of IHO. The developed assay presented a very simple operating procedure and a rapid analysis time of around 10 min. The developed assay also exhibited good selectivity and a low limit of detection (LOD) of 0.005 mM for detecting IHO. Moreover, the developed assay showed comparable accuracy and precision to the high-performance liquid chromatography-diode array detector (HPLC-DAD) method when used for the rapid determination of IHO in river water and human urine samples. The recoveries of IHO at three spiking levels were in the range of 91.5–106.3% with relative standard deviation (RSD) values below 6.39%.

Search for new diagnostic markers of renal function in pregnant women

Over the past few years, the prevalence of chronic kidney disease in pregnant women has been increasing rapidly, which is one of the most important problems of obstetrics, urology, and nephrology. The severity of the disease is assessed by a decrease in glomerular filtration rate (GFR). However, modern formulas of GFR give errors, therefore, it is necessary to search for new diagnostic markers of renal function in pregnant women. It is believed that elimination of cystatin C from the circulation by more than 99% is carried out by the kidneys. In an intact form, this molecule is not thought to undergo either tubular reabsorption or secretion. In this sense, cystatin C can be considered an almost ideal marker of GFR. This article discusses the possibilities of using cystatin C as a marker of renal function in pregnant women.

Iohexol assay for direct determination of glomerular filtration rate: optimization and development of an HPLC-UV method for measurement in serum and urine

Determination of glomerular filtration rate (GFR) is considered the best indicator of renal function. Iohexol, a non-ionic contrast agent, is currently considered to be a reference marker since it meets all the requirements of an ideal GFR marker. The aim of our work is to develop and optimize a method for iohexol measurement by HPLC-UV. The results showing the following optimal conditions : a mobile phase with water and 5% of acetonitrile, a C18 analytical column (250 × 4 mm, 5 μm particle size) with a temperature of 40 °C and a flow rate of 1 ml/min. Serum samples are deproteinized by addition of perchloric acid (6%), while urine samples are only diluted. For both matrices, the method is linear (r2 > 0.99) and the recovery is > 98%. For selectivity, no interfering endogenous components at the retention time of iohexol was observed. The results of the matrix effect showed a clinically acceptable variation in most concentration levels except for 100 μg/mL, in urine, where the effect was slightly present. Iohexol stability in urine decreases significantly only after 3 freeze–thaw cycles and after freezing at −80 °C for two months. According to those findings results this method is simple, specific, linear, precise and robust, which allows its application for the direct measurement of the GFR after its analytical validation.

Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?

While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

Glomerular filtration rate estimation in renal transplant patients based on serum cystatin-C levels: Comparison with other markers of glomerular filtration rate

Purpose The assessment of glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin-C, a cysteine protease inhibitor, which can be measured by light-scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Conversely, many endogenous markers that are widely used for the estimation of GFR such as serum creatinine (SCr) are not ideal. The present study was undertaken to evaluate the clinical application of serum cystatin-C (CysC) as a new marker of GFR in renal transplant patients. Methods Eighteen patients (9 men) were enrolled in the study (mean age: 46.35, range: 31–67 years) to measure serum CysC levels and compare them, with SCr, creatinine clearance (CCr), as well as the Cockcroft-Gault equation (CG) or the MDRD as indicator of GFR. Spearman's correlation coefficient was used to determine the relationship between CysC and other markers. Results There was a significant negative correlation between serum CysC and CCr (r = −0.768). Moreover, the CysC level was negatively correlated with CG (r = −0.854), positively correlated with SCr (r = 0.629), and negatively correlated with MDRD (r = −0.604). Conclusions These results indicate that measurement of serum cystatin-C was useful and accurate to estimate GFR in renal transplant patients. The recent literature confirms our data although there are concerns about nonrenal influence on this test. Although serum CysC can generally be recommended as a marker for GFR, our study is still in progress seeking to validate the conclusions in a larger number of patients.

GLOMERULAR FILTRATION RATE ESTIMATION IN RENAL TRANSPLANT PATIENTS BASED ON SERUM CYSTATIN C LEVELS. COMPARISON WITH OTHER MARKERS OF GLOMERULAR FILTRATION RATE.

Abstract Purpose The assessment of glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin-C, a cysteine protease inhibitor, which can be measured by light-scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Conversely, many endogenous markers that are widely used for the estimation of GFR such as serum creatinine (SCr) are not ideal. The present study was undertaken to evaluate the clinical application of serum cystatin-C (CysC) as a new marker of GFR in renal transplant patients. Methods Eighteen patients (9 men) were enrolled in the study (mean age: 46.35, range: 31–67 years) to measure serum CysC levels and compare them, with SCr, creatinine clearance (CCr), as well as the Cockcroft-Gault equation (CG) or the MDRD as indicator of GFR. Spearman's correlation coefficient was used to determine the relationship between CysC and other markers. Results There was a significant negative correlation between serum CysC and CCr (r = −0.768). Moreover, the CysC level was negatively correlated with CG (r = −0.854), positively correlated with SCr (r = 0.629), and negatively correlated with MDRD (r = −0.604). Conclusions These results indicate that measurement of serum cystatin-C was useful and accurate to estimate GFR in renal transplant patients. The recent literature confirms our data although there are concerns about nonrenal influence on this test. Although serum CysC can generally be recommended as a marker for GFR, our study is still in progress seeking to validate the conclusions in a larger number of patients.

Developments in the assessment of glomerular filtration rate

The assessment of the glomerular filtration rate (GFR) is the most commonly used test of renal function. The accepted reference procedure employs an exogenous clearance marker whilst the most popular test is that of serum or plasma creatinine. All of these tests have limitations, although the surrogate endogenous markers are the most practical. Cystatin C, a low molecular weight protein which can be measured by light scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Data on reference ranges indicate that circulating cystatin C levels reflect the variation in GFR throughout life and the marker demonstrates a better correlation with the reference procedure than serum creatinine.

The Search Continues—An Ideal Marker of GFR

The glomerular filtration rate (GFR) is generally considered the best measure of renal function despite the fact that the kidney performs an array of duties, including salt and water balance, erythropoiesis, bone metabolism, electrolyte homeostasis, and blood pressure control. GFR is traditionally measured as the renal clearance of a particular substance from plasma and is expressed as the volume of plasma that can be completely cleared of that substance in a unit of time. The ideal marker for GFR determinations would appear endogenously in the plasma at a constant rate, be freely filtered at the glomerulus, be neither reabsorbed nor secreted by the renal tubule, and undergo no extrarenal elimination. Although the ideal marker for measuring GFR has yet to be found, these characteristics can be useful benchmarks for comparing the advantages and disadvantages of new methods for GFR quantification. Measurement of urea marked the beginning of efforts to quantify renal function with its isolation by Rouelle in 1773 (1). Subsequently, Strauss introduced blood urea as a diagnostic test for renal disease in 1903. The concept of clearance as a measure of renal function followed in 1929 (2) and was subsequently extended to creatinine in the early 1930s (1). Blood urea nitrogen (BUN) concentration is generally recognized to …

Extrarenal plasma clearance of iohexol and other markers of normal and reduced glomerular filtration rate.

T he ~clearance of markers of glomerular filtration rate (GFR) from plasma is used to determine tile GFR of the two kidneys in cooperation. The ideal GFR marker should have glomemlar, filtration as the only mechanism clearing it from plasma. The ideal GFR marker does not exist today, as all markers have some extrarenal clearance. The demands on the presently used GFR markers are maximal clearance by glomerular filtration, minimal excretion and reabsorption by the renal tubuli, and minimal extrarenal clearance. Two techniques used to determine GFR are the renal plasma clearance technique (often called simply renal clearance) and the total plasma clearance technique (often called simply plasma clearance). Both clearance techniques require plasma samples of tile GFR marker and use tile marker concentrat ions in those samples and various pharmacokinetic models to make mathematical formulas that describe tile plasma concentrat ion of the marker over time. The mathematical formulas then are used to calculate an area under the plasma concentrat ion curve (the vertical axis is plasma concentration of marker and the horizontal axis is time). The renal clearance technique gives tile GFR after dividing the amount of marker collected in the urine in a given period by tile area under the curve in tile same period. The major drawback of renal clearance is its sensitivity to inaccurate urine sampling of the marker and the occurrence of residual urine in the bladder. This may give false low or false high GFR values. The plasma clearance technique gives GFR after dividing the dose of the marker by tile area under the curve in the period from time of injection to infinity. The major drawback of plasma clearance is its ignorance of tile extrarenal excretion of the marker, which produces false high GFR values. We sought to improve the determination of GFR with plasma clearance techniques by investigating the extrarenal clearance of tile marker at different levels of GFR. If the extrarenal clearance of a GFR marker in a species is fairly constant at different levels of GFR, this known extrarenal clearance in that species could be subtracted from tile plasma clearance of the marker to get clearance values closer to tile true GFR. If the results show that the extrarenal This work was supported by the Swedish State (Medical Research Council) and by Nycomed Imaging (Oslo, Norway). From the Departments of 1Diagnostic Radiology, 2Nephrology, and 3Radiophysics, Malm0 University Hospital, Matm0, Sweden. Address reprint requests to T. Alm~n, MD, PhD, Department of Diagnostic Radiology, Maim0 University Hospital, S-205 02 Maim0, Sweden.