Reference Glomerular Filtration Rate Research Articles

Improved GFR estimation by combined creatinine and cystatin C measurements

Plasma creatinine may not reflect glomerular filtration rate (GFR) especially in the early stages of chronic kidney disease (CKD). Plasma cystatin C (cysC), however, has the potential to more accurately determine early GFR reduction. We sought to improve the creatinine-based GFR estimation by including cysC measurements. We derived a reference GFR from standard dual plasma sampling (99m)Tc-DTPA clearance in a training cohort of 376 randomly selected adult Chinese patients with CKD. We compared reference values to estimated GFR and applied multiple regression models to one equation based solely on cysC, and to another combining plasma creatinine (Pcr) and cysC measurements of the training cohort. The results were validated by testing an additional 191 patients. The difference, precision, and accuracy of the two estimates were compared with the modified Modification of Diet in Renal Disease (MDRD) equation for Chinese patients, and another estimate combining cysC and modified MDRD calculations. The estimated GFR combining Pcr and cysC measurements more accurately matched the reference GFR at all stages of CKD than the other equations, particularly in patients with near-normal kidney function.

A Practical Method of Measuring Glomerular Filtration Rate by Iohexol Clearance Using Dried Capillary Blood Spots

Background: Exogenous tracer-based methods of measuring glomerular filtration rate (GFR) are difficult to perform, whilst creatinine-based estimation formulae are inaccurate. Methods: We assessed a new technique of measuring iohexol clearance using timed dried capillary blood spots. A reference GFR was measured in 81 subjects (GFR 15–124 ml/min/1.73 m²) by iohexol clearance using three venous samples (2, 3 and 4 h after an intravenous bolus). GFR was estimated by six test methods; iohexol clearance using (i) 3 blood spots (2, 3, 4 h); (ii) 2 blood spots (2, 4 h) and (iii) 1 blood spot (4 h); (iv) the Modification of Diet in Renal Disease (MDRD) formula; (v) the Cockcroft-Gault formula, and (vi) a formula estimating GFR from serum cystatin C concentration. For each test method the bias and precision were calculated as the mean and standard deviation (SD) of the ‘GFR differences’ (test method GFR – reference GFR). Results: The limits of agreement (bias ±1.96 × SD; in ml/min/1.73 m²) were: (i) 1.1 ± 15.1 for 3-spot iohexol clearance; (ii) 0.6 ± 14.9 for 2-spot iohexol clearance; (iii) 4.5 ± 21.2 for 1-spot iohexol clearance; (iv) –15.7 ± 33.3 for the MDRD formula; (v) –9.6 ± 32.9 for the Cockcroft-Gault formula, and (vi) –12.1 ± 31.7 for the Cystatin C formula. The accuracy of all six test methods was similar among individuals with GFR <60 ml/min/ 1.73 m²; however, in individuals with GFR ≧60 ml/min/ 1.73 m², the MDRD, Cockcroft-Gault and Cystatin C formulae were all imprecise and systematically underestimated GFR. Conclusions: Blood spot iohexol clearance provides a potentially practical method of estimating GFR accurately in large-scale epidemiological studies especially among individuals without established chronic kidney disease.

Development of formulae for accurate measurement of the glomerular filtration rate by renal dynamic imaging

Currently, the widely adopted renal dynamic imaging in clinical practice uses Gates' method to calculate the glomerular filtration rate (GFR), but many researchers have proven that Gates' method may result in bias. Thus, this article explores alternative improved formulae to calculate GFR by renal dynamic imaging. Three hundred and sixty-seven patients were selected and their GFR values were measured using renal dynamic imaging and the two-plasma method with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) as the imaging agent. With the two-plasma GFR as reference value, two equations were obtained from linear and non-linear regression analyses between the renal uptake percentage and two-plasma GFR. The 367 patients were divided into two random groups, with the first group used to derive the regression formulae and the second to verify the formulae. Finally, all patients were studied to derive the formulae to calculate GFR. The comparison of our formulae with the commonly used Gates' formula was conducted by the Bland-Altman method. The linear and non-linear GFR formulae were as follows: GFR (ml/min/1.73 m2)=(631.633 x renal uptake percentage - 2.040) x 1.73/BSA (BSA, body surface area) and GFR (ml/min/1.73 m2)=(-1996.585 x renal uptake percentage2 + 1013.526 x renal uptake percentage - 12.739) x 1.73/BSA, respectively. The biases of the GFR values calculated using the linear and non-linear formulae and Gates' formula relative to the two-plasma GFR were -2.5 +/- 19.1 ml/min/1.73 m2, -2.0 +/- 19.3 ml/min/1.73 m2 and 3.4 +/- 19.4 ml/min/1.73 m2, respectively. The GFR values calculated using our new formulae correlate better with the reference GFR value than does GFR calculated by Gates' formula, and the GFR values measured using the non-linear formula are more accurate than those obtained using the linear formula.

The accuracy of cystatin C and commonly used creatinine‐based methods for detecting moderate and mild chronic kidney disease in diabetes

The accuracy of measuring serum cystatin C levels for detecting various stages of chronic kidney disease (CKD) in diabetes is still unclear. In a cross-sectional study of 251 subjects, a reference glomerular filtration rate (GFR) was measured using (99c)Tc-DTPA plasma clearance (iGFR). Multivariate analysis was used to identify independent clinical and biochemical associations with serum cystatin C and iGFR levels. The diagnostic accuracy of cystatin C and commonly used creatinine-based methods of measuring renal function (serum creatinine, the MDRD four-variable and Cockcroft-Gault formulae) for detecting mild and moderate CKD was also compared. In the entire study population the same five variables, age, urinary albumin excretion rates, haemoglobin, history of macrovascular disease and triglyceride levels were independently associated with both cystatin C and iGFR levels. A serum cystatin C level cut-off > 82.1 nmol/l (1.10 mg/l) had the best test characteristics as a screening tool for detecting moderate CKD (< 60 ml/min per 1.73 m(2)) when compared with creatinine-based methods. At the upper threshold for mild CKD (< 90 ml/min per 1.73 m(2)), cystatin C also had greater diagnostic accuracy than creatinine, but had similar diagnostic accuracy when compared with creatinine-based formulae for predicting renal function. This study suggests that the clinical and biochemical parameters associated with serum cystatin C levels are closely linked to those associated with GFR and highlights the potential usefulness of screening for moderate or mild CKD in subjects with diabetes by simply measuring serum cystatin C levels.

Comparison of 99mTc-DTPA renal dynamic imaging with modified MDRD equation for glomerular filtration rate estimation in Chinese patients in different stages of chronic kidney disease

The renal dynamic imaging method (modified Gate's method) with (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) is simple and less time consuming for glomerular filtration rate (GFR) estimation than other methods. However, its diagnostic performance as a surrogate marker of GFR is questioned increasingly. Recently, the modified Modification of Diet in Renal Disease (MDRD) study equation based on data from Chinese patients of chronic kidney disease (CKD) showed significant performance improvement. In the present study, the renal dynamic imaging methods and the modified abbreviated MDRD equation were compared with the plasma clearance method. Four hundred and eighty two patients with CKD were selected. GFR were estimated simultaneously using three methods: (i) modified Gate's method (gGFR); (ii) the modified abbreviated MDRD equation (c-aGFR) and (iii) dual plasma sampling method (rGFR). Using rGFR as the reference method, gGFR and c-aGFR were compared with rGFR in each stage of CKD. Both gGFR and c-aGFR were correlated well with rGFR (r(gGFR) = 0.81 and r(c-aGFR) = 0.90, P < 0.001). In the overall performance, c-aGFR had less bias (849.5 vs 933.1 arbitrary units), higher precision (57 vs 78.4 ml/min/1.73 m(2)) and higher accuracy than gGFR. For gGFR, the 15, 30 and 50% accuracies were 32.4, 56.0 and 79.1%, respectively; for c-aGFR, the corresponding accuracy rose to 43.2%, 75.5% and 90.9%, respectively. In each stage of CKD, the modified abbreviated MDRD equation also outperformed the modified Gate's method in the GFR estimation. Our results indicated that the performance of the renal dynamic imaging in total GFR estimation was not better than the modified abbreviated MDRD equation in our patient group, and should not be used as a surrogate marker of GFR, especially in clinical trials. We presume that the dynamic renal imaging methods for estimation of GFR can be improved by using proper reference GFR, more adequate background subtraction and soft-tissue attenuation correction, in a relatively larger sample size.

Development of an outpatient finger-prick glomerular filtration rate procedure suitable for epidemiological studies

Development of an outpatient finger-prick glomerular filtration rate (GFR) procedure suitable for epidemiological studies. In clinical practice, reference GFR procedures are rarely used; in large-scale research studies, a great deal of effort and experience is required to obtain them, which is a considerable disincentive to using GFR as an end point. The major problem for both clinical staff and the subject is the length of time that the procedure takes, requiring continuous attendance in the outpatient clinic or its vicinity. Using iohexol as a marker, we therefore propose an alternative approach, which addresses this fundamental deterrent to a more widespread use of GFR measurement. Eighty-two GFR measurements were performed in a mixture of healthy subjects and patients with differing degrees of renal impairment with a wide range of GFRs. Serum was obtained from blood samples to enable a reference GFR to be calculated. Blood spots were collected on filter paper at the same intervals (120, 180, and 240 min), allowed to dry, and then sent through the post. Serum and blood spots were analyzed simultaneously for each individual by automated reverse-phase high-pressure liquid chromatography. Standard linear regression analyses confirmed a good agreement (r2 = 0.953) between the iohexol serum GFR and iohexol blood spots GFR. Bland-Altman analysis confirmed that there was no concentration bias. Paired comparisons (Wilcoxon's paired signed rank test) showed no significant difference between the two measurements. Capillary sampling is simple, effective, and significantly reduces the time and costs of performing plasma clearance GFR measurements. This approach will make the GFR measurement more accessible for clinical practice and large-scale epidemiological studies may become feasible.

Glomerular filtration rate measured using the Patlak plot technique and contrast‐enhanced dynamic MRI with different amounts of gadolinium‐DTPA

We determined the optimum gadolinium (Gd)-DTPA dose and time window for calculating the glomerular filtration rate (GFR) using contrast-enhanced (CE) dynamic MRI and the Patlak plot technique. Twelve adult volunteers with healthy kidneys were included in the study. As a reference method the GFR was measured by iopromide plasma clearance. A three-dimensional gradient-echo (GRE) sequence with a flip angle of 50 degrees was used for MRI. Signal was measured using a body surface coil with four elements. Each volunteer was examined on four days using 2 mL, 4 mL, 8 mL, or 16 mL of Gd-DTPA 0.5 mmol/mL dissolved with sodium chloride (NaCl) 0.9% to a total of 60 mL. The injection rate was 1 mL/second. A Patlak plot was calculated from the kidney and aorta signals. The mean reference GFR was 133 mL/min (min-max, 116-153 mL/min). The best correlation of GFR calculated from MRI data compared to the reference method was found in a time window 30-90 seconds after aortic signal rise using 16 mL Gd-DTPA. Pearson's correlation coefficient was r = 0.83, and the standard deviation (SD) from the line of regression was 10.5 mL/minute. We found a significantly lower average GFR(MR) using 16 mL Gd-DTPA compared to 4 mL and 2 mL in the late time window 60-120 seconds post aortic rise. A dose of 16 mL Gd-DTPA was optimal for measuring GFR using dynamic MRI and the Patlak plot technique. The slope should be measured in a time window of 30-90 seconds post aortic rise.

Assessing Suitability for Renal Donation: Can Equations Predicting Glomerular Filtration Rate Substitute for a Reference Method in the Indian Population?

Background: Accurate measurement of donor renal function has important long-term implications for both the donor and recipient. As the use of recommended filtration markers is limited by cumbersome and costly techniques, renal function is typically estimated using 24-hour urinary creatinine clearance (urine-CrCl). Prediction equations used for rapid bedside estimation of glomerular filtration rate (GFR) are simple and overcome the inaccuracies of urinary collection and, if validated, can expedite the donor workup besides reducing the cost. We assessed the suitability of urine-CrCl and prediction equations for evaluating potential Indian renal donors. Methods: 173 consecutive renal donors were enrolled. The predictive capabilities of the Cockcroft and Gault equation for creatinine clearance (CrCl) corrected for body surface area (CG-CrCl), CG-CrCl corrected for GFR (CG-GFR), MDRD-1, MDRD-2 and urine-CrCl were evaluated with ^99mTc-diethylenetriaminepentaacetic acid (DTPA)-GFR as reference GFR. Results: The study population had a mean age of 44.1 years with 74% being females. Mean DTPA-GFR was 83.85 ml/min/1.73 m². The median percent absolute difference was most with urine-CrCl and least with CG-GFR (21.84 and 13.82). The Pearson’s correlation varied from 0.08 to 0.26 (urine-CrCl and MDRD-1). The precision was most with MDRD-1 and least with urine-CrCl (0.07 and 0.01). The bias was least with CG-GFR and most with MDRD-2 (1.34 and 17.16). The number of subjects with predicted GFR values within 30% of DTPA was most with MDRD-1 (86%) and least with urine-CrCl (69%). The sensitivity for selecting a donor with a GFR of ≧80/ml/min/1.73 m² was the most with CG-GFR (65.7%), while specificity was maximum with MDRD-2 (90.1%). Conclusion: Our results in potential Indian renal donors show that of all the prediction equations MDRD-1 is the most precise and accurate, while CG-GFR is the least biased. However, the poor correlation and level of error exhibited by these equations makes them suboptimal for donor evaluation.

Prediction of two-sample99mTc-diethylene triamine pentaacetic acid plasma clearance from single-sample method

To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1.73 m2, the diagnostic sensitivity of a cut off value of aGFR = 45 ml/min/1.73 m2 was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM. When GFR > or =30 ml/min/1.73 m2, tGFR can be predicted from sGFR, which will simplify the reference GFR measurement in clinical trials. sGFR becomes widely scattered when tGFR is less than 30 ml/min/1.73 m2. To obtain reliable reference GFR values, it is recommended that DPSM be used in clinical trials when aGFR is less than 45 ml/min/1.73 m2.

Susceptibility of glomerular filtration rate estimations to variations in creatinine methodology: a study in older patients

It is recommended that measurement of serum creatinine should be supplemented with a creatinine-based estimation of glomerular filtration rate (GFR). The influence of creatinine methodology on these estimates is not always appreciated. We have studied differences in creatinine methods and their influence on GFR estimation specifically in older people. In all, 46 older patients (mean age 80 y, range 69-92 y) with predominantly mild or moderate kidney disease were studied. Serum creatinine was measured using a rate Jaffe method and two different enzymatic methods. Isotope dilution mass spectrometry served as the reference creatinine method. GFR was estimated using both the Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault formulae: a 51Cr-EDTA GFR estimation served as the reference GFR method. Both enzymatic methods produced creatinine results that were significantly different (P<0.001) from the reference method. The Jaffe method over- and underestimated creatinine at low and high concentrations, respectively. The most likely explanation for these differences relates to standardization of the assays. Irrespective of creatinine method, the Cockroft and Gault formula tended to underestimate GFR, and the MDRD formula to overestimate GFR. Use of the differing creatinine methods to estimate GFR produced predictable biases of the estimate, with mean GFR estimates varying by 14% across the creatinine methods. Estimates of GFR depend critically upon the accuracy and precision of the creatinine measurement used in their calculation.

Renal function impairment in workers previously exposed to cadmium.

Cadmium-induced renal effects were followed (1989) in 16 workers previously exposed to cadmium, who had been shown 5 years earlier to have had tubular damage; all but 1 worker had persistent tubular damage (beta 2-microglobulin > 60 micrograms/mmol creatinine). The mean glomerular filtration rate (GFR) decreased from 77.3 to 71.7 ml/min/1.73 m2, which is 2.0 ml/min more than would have been expected from aging only. There was a negative correlation between loss of tubular function (relative clearance of beta 2-microglobulin) and the ratio of observed versus reference GFRs in accordance with a 1984 study. The results confirm that cadmium-induced tubular damage is irreversible. They also suggest that the glomerular dysfunction after cadmium exposure is irreversible and progressive also after exposure stops. A nonsignificant correlation was found between cumulative cadmium exposure and decreased GFR.

Measurement of glomerular function during cisplatin therapy.

1. Creatinine-based methods for measuring glomerular filtration rate (GFR) were compared with the plasma clearance of 99mTc DTPA as an accurate index of GFR in patients prior to and during cisplatin therapy. 2. Measured creatinine clearances using either unsupervised 24 h or supervised 4 h collections correlated less well with the reference GFR than did predicted creatinine clearances derived from serum creatinine using formulae or a nomogram. 3. Predicted creatinine clearance appears to be at least as sensitive as measured creatinine clearance for screening GFR in patients receiving cisplatin. However, owing to the inherent inaccuracy in any creatinine-based method, if the prediction is within 20% of the value at which dose reduction of cisplatin is considered, an isotopically determined GFR should be carried out to optimise dosage adjustments.

A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, I: establishment of a body weight-related formula for the distribution volume of iohexol

This study was performed in order to develop a method for estimation of the glomerular filtration rate (GFR) from a single plasma sample based upon the plasma disappearance rate of the non-ionic contrast medium iohexol. The apparent distribution volume for iohexol was measured in 100 infants and children and used for establishment of a weight-related empirical formula for the distribution volume. Using the distribution volume obtained by this formula, a preliminary GFR was calculated from the iodine concentration measured in a plasma sample taken 3 h after injection of iohexol. When this estimate was corrected by another empirically established correction factor, a high degree of agreement was found between a GFR reference method and the 3-h single plasma sample method. In another group of 13 children the 3-h single plasma sample GFR was estimated twice with a 2-day interval, and the day-to-day variations were found to be similar to those obtained with other standard methods.