Plasma Clearance Method Research Articles

GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques.

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.

Comparison of Two Methods for Estimation of Glomerular Filtration Rate: Double Plasma Sampling Method and Renography with 99mTc-DTPA

: Glomerular filtration rate (GFR) is a crucial metric that is widely used to evaluate kidney function. A method with high accuracy to estimate GFR is renal scintigraphy using radiopharmaceutical 99m-technetium diethylenetriamine pentaacetic acid (99mTc-DTPA) in SPECT (single-photon emission tomography) system. In addition, there is another method, the double plasma sampling method (DPSM) using the same radiopharmaceutical to determine GFR. This study aims to evaluate and compare GFR results collected from 42 patients by the two methods. The result indicates that the two methods have a high correlation with r = 0.857 and r = 0.711 (p&lt;0.05), respectively in the two patient groups. Therefore, DPSM shows a high possibility for clinical application in certain situations.&#x0D; Keywords:&#x0D; 99mTc-DTPA, glomerular filtration rate, renography.&#x0D; References&#x0D; [1] K. Itoh, Comparison of Methods for Determination of Glomerular Filtration Rate: Tc-99m-DTPA Renography, Predicted Creatinine Clearance Method and Plasma Sample Method, Annals of Nuclear Medicine, Vol. 17, No. 7, 2003, pp. 561-565, https://doi.org/10.1007/BF03006669.[2] J. O. Hernandez, A. R. Torres, F. C. Rodriguez, Comparison of Four Methods for Measuring Glomerular Filtration Rate by Inulin Clearance in Healthy Individuals and Patients with Renal Failure, Nefrologia, Vol. 30, No. 3, 2010, pp. 324-330, https://doi.org/10.3265/Nefrologia.pre2010.Mar.10238.[3] L. A. Stevens, A. S. Levey, Measured GFR as a Confirmatory Test for Estimated GFR, Journal of the American Society of Nephrology, Vol. 20, No. 11, 2009, pp. 2305-2313, https://doi.org/10.1681/asn.2009020171.[4] F. J. Hoek, F. A. Kemperman, R. T. Krediet, A Comparison Between Cystatin C, Plasma Creatinine and the Cockcroft And Gault Formula for the Estimation of Glomerular Filtration Rate, Nephrology Dialysis Transplantation, Vol. 18, No. 10, 2003, pp. 2024-2031, https://doi.org/10.1093/ndt/gfg349.[5] W. S. Watson, A Simple Method of Estimating Glomerular Filtration Rate, European Journal of Nuclear Medicine and Molecular Imaging, Vol. 19, No. 9, 1992, pp. 827, https://doi.org/10.1007/bf00182829.[6] P. W. Blue, J. H. Jackson, N. Ghaed, Re: Glomerular Filtration Rate Determined in Conjunction with Routine Renal Scanning, Radiology, Vol. 156, No. 2, 1985, pp. 553, https://doi.org/10.1148/radiology.156.2.553-a.[7] G. F. Gates, Split Renal Function Testing Using 99m-Tc DTPA. A Rapid Technique for Determining Differential Glomerular Filtration, Clinical Nuclear Medicine, Vol. 8, No. 9, 1985, pp. 400-407, https://doi.org/10.1097/00003072-198309000-00003.[8] K. W. Tobis et al., Difference in Estimated GFR with Two Different Formulas in Elderly Individuals, International Urology and Nephrology, Vol. 38, No. 2, 2006, pp. 381-385, https://doi.org/10.1007/s11255-006-0065-7.[9] C. D. Russell et. Al., Measurement of Glomerular Filtration Rate: Single Injection Plasma Clearance Method Without Urine Collection, Journal of Nuclear Medicine, Vol. 26, No. 11, 1985, pp. 1243-1247.[10] M. J. Surma, A. Plachcinska, J. Kusmierek, Modification of a Two Blood Sample Method Used for Measurement of GFR with 99mTc-DTPA, Nuclear Medicine Review - Central &amp; Eastern Europe, Vol. 21, No. 1, 2018, pp. 43-47, https://doi.org/10.5603/nmr.2018.0013.[11] J. S. Fleming et al., Guidelines for the Measurement of Glomerular Filtration Rate Using Plasma Sampling, Nuclear Medicine Communications, Vol. 25, No. 8, 2004, pp. 759-769, https://doi.org/10.1097/01.mnm.0000136715.71820.4a.[12] A. Piepsz et al., Guidelines for Glomerular Filtration Rate Determination in Children, European Journal of Nuclear Medicine and Molecular Imaging, Vol. 28, No. 3, 2001, pp. BP31-BP36.&#x0D;

Modified Schwartz formula and 99mTc-DTPA plasma clearance methods to calculate glomerular filtration rate in critically ill children.

Studies comparing the modified Schwartz formula with measured GFR (m-GFR) are lacking in critically ill children. This prospective cohort study enrolled children aged 1 month to 12 years, within 24 h of admission. m-GFR measured by technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) and calculated by Russell's two-sample slope-intercept method. Serum creatinine was estimated by modified Jaffe method and estimated GFR (e-GFR) calculated by modified Schwartz formula. The primary outcome was to find agreement between the two methods. Bias, precision, and accuracy were calculated. Secondary outcomes were the incidence of AKI (by p-RIFLE criteria) and the difference between the two methods to diagnose AKI. A total of 208 pairs were analyzed. e-GFR showed good agreement with m-GFR with a mean bias of -4.37 ml/min/1.73 m2 and precision (SD of bias) of 33.07, 95% limit of agreement -69.18 to 60.45, and intraclass correlation of 74% (95%CI 66-80%, P < 0.001). e-GFR underestimated m-GFR by 19.8% (95% CI 7.9-31.7%). Accuracy of e-GFR values within 10%, 20%, and 30% of m-GFR were 68.3%, 72.6%, and 78.8%, respectively. Incidence of AKI within 24 h was 60.1% by e-GFR and 54.3% by m-GFR (kappa 0.569, P < 0.001; sensitivity of 85.8%, 95%CI (78-91.7%). The modified Schwartz formula shows good agreement with 99mTc-labeled DTPA double plasma sample clearance method for calculating GFR in critically ill children aged 1 month to 12 years. The underestimation of GFR should be kept in mind while applying the formula at the bedside in PICU. Protocol accessible at Clinical Trial Registry of India (CTRI) www.ctri.nic.in . (Trial Registered Prospectively and Registration No. CTRI/2017/10/010014) ([Registered on: 06/10/2017] Trial Registered Prospectively.) (Title "Measured glomerular filtration rate using Diethylenetriaminepentaacetic acid (DTPA) renal scan versus estimated glomerular filtration rate using modified Schwartz formula in critically ill children: A prospective observational, analytical study."). A higher resolution version of the Graphical abstract is available as Supplementary information.

The correlation between kidney volume and measured glomerular filtration rate\xa0in an Asian ADPKD population: a prospective cohort study

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder that leads to end stage renal disease (ESRD). Cyst expansion in ADPKD is strongly associated with the decline in renal function. However, the correlation between total kidney volume (TKV) and glomerular filtration rate (GFR) at an early stage has not been well demonstrated. There is growing evidence that utilization of estimated GFR (eGFR) may induce misleading information in a population with near normal renal function. Therefore, a more accurate method is essential.MethodsA prospective cohort of ADPKD patients was conducted with clinical data and laboratory collection. Measured GFR (mGFR) was assessed by iohexol plasma clearance method using ultra performance liquid chromatography. eGFR was calculated using the CKD-EPI equation. Kidney volumes were evaluated using MRI imaging protocol.ResultsThirty two patients completed the study. The mean age was 56 years old. The mean initial mGFR was 83.8 mL/min/1.73m2. The mean change in mGFR per year was –2.99 mL/min/1.73m2/year. The mean initial height-adjusted TKV (htTKV) was 681.0 mL/m. The mean percentage change in htTKV per year (%ΔhtTKV/y) was 4.77 %/year. mGFR had a better association with clinical parameters than eGFR. Initial mGFR was significantly and inversely correlated with initial htTKV and age. The percentage change in mGFR per year was significantly and inversely correlated with the %ΔhtTKV/y and 24-hr urine albumin. The %ΔhtTKV/y was significantly correlated with initial htTKV.ConclusionsOur studies demonstrated that mGFR using iohexol is a more reliable and accurate method than eGFR for evaluating GFR changes in the early stages of ADPKD patients. There is a strong inverse correlation between kidney volume and mGFR in an Asian ADPKD population. The initial htTKV is a good predictor of kidney volume progression. The %ΔhtTKV/y is a good early surrogate marker for the decline in renal function. 24-hr urine albumin is also a good indicator for renal progression.

Comparison of 51Cr-EDTA and 99mTc-DTPA for glomerular filtration rate measurement.

The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. Mean age was 52.2 ± 14.5years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0mL/min, respectively, with a mean bias of 2.00 ± 2.25mL/min, an accuracy within 10% of 95% [95% CI 91-99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6mL/min, respectively, with a mean bias of 1.96 ± 3.32mL/min, an accuracy within 10% of 91% [95% CI 85-97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

P0110 / #800: MEASURED GLOMERULAR FILTRATION RATE USING DTPA PLASMA CLEARANCE VERSUS ESTIMATED GLOMERULAR FILTRATION RATE USING MODIFIED SCHWARTZ FORMULA IN CRITICALLY ILL CHILDREN: A OBSERVATIONAL STUDY

Aims & Objectives: To study the strength of agreement between the Measured (m-GFR) by 99mTc-DTPA renal clearance and Estimated GFR (e-GFR) by modified Schwartz formula in critically ill children in PICU. Methods: Children aged 1 month to 12 years admitted in PICU, were included in the study within 24 hours of admission to PICU with stable hemodynamic parameters. One mCi (mile Curie) of freshly prepared 99mTc-DTPA dispensed in pre-weighed syringes was injected intravenously followed by 2 ml of normal saline flush.Two blood samples for GFR estimation and simultaneous SCr were taken at two hour and four-hour following injection in a heparinized vial. The counting of samples was done within by Russell’s two-sample slope-intercept method was performed. GFR was calculated as follows by using the modified Schwartz formula, e-GFR = k x L / Sr Results: Bland–Altman plot for GFR by 99mTc-DTPA plasma clearance and bedside Schwartz method showed a mean difference of 4.538 (95% confidence interval [CI] = -0.388–8.895). The limit of agreement ranged from -61.32to 69.87. ICC coefficient in our study showed moderate correlation in the whole study group, in subjects more than 24 months of age and in patients suffering from AKI.One thirty-one (64.8%) patients were diagnosed with AKI as per p-RIFLE classification.One hundred twenty-seven patients (62.87%) diagnosed AKI within 24 hours of PICU stay by using bedside Schwartz formula and 117 of them also matching AKI criteria if GFR was considered as per m-GFR value. Conclusions: We found good agreement between measured and estimated GFR in pediatric patients.

The failure of glomerular filtration rate estimating equations among obese population.

BackgroundObesity is a major public health with increasing numbers of obese individuals are at risk for kidney disease. However, the validity of serum creatinine-based glomerular filtration rate (GFR) estimating equations in obese population is yet to be determined.MethodsWe evaluated the performance of the reexpressed Modification of Diet in Renal Disease (MDRD), reexpressed MDRD with Thai racial factor, Thai estimated GFR (eGFR) as well as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations among obese patients, defined as body mass index (BMI) ≥25 kg/m2 with the reference measured GFR (mGFR) determined by 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method. Serum creatinine levels were measured using standardized enzymatic method simultaneously with GFR measurement. The statistical methods in assessing agreement for continuous data including total deviation index (TDI), concordance correlation coefficient (CCC), and coverage probability (CP) for each estimating equation were compared with the reference mGFR. Accuracy within 10% representing the percentage of estimations falling within the range of ±10% of mGFR values for all equations were also tested.ResultsA total of 240 Thai obese patients were finally recruited with mean BMI of 31.5 ± 5.8 kg/m2. In the total population, all eGFR equations underestimated the reference mGFR. The average TDI values were 55% indicating that 90% of the estimates falling within the range of -55 to +55% of the reference mGFR. The CP values averaged 0.23 and CCC scores ranged from 0.75 to 0.81, reflecting the low to moderate levels of agreement between each eGFR equation and the reference mGFR. The proportions of patients achieving accuracy 10% ranged from 23% for the reexpressed MDRD equation to 33% for the Thai eGFR formula. Among participants with BMI more than 35 kg/m2 (n = 48), the mean error of all equations was extremely wide and significantly higher for all equations compared with the lower BMI category. Also, the strength of agreement evaluated by TDI, CCC, and CP were low in the subset of patients with BMI ≥35 kg/m2.ConclusionEstimating equations generally underestimated the reference mGFR in subjects with obesity. The overall performance of GFR estimating equations demonstrated poor concordance with the reference mGFR among individuals with high BMI levels. In certain clinical settings such as decision for dialysis initiation, the direct measurements of GFR are required to establish real renal function among obese population.

Validation of non-invasive transcutaneous measurement for glomerular filtration rate in lean and obese C57BL/6J mice.

The measurement of glomerular filtration rate (GFR) in experimental rodents is pivotal to understanding the progression of kidney disease and benefits of treatment strategies. A non-invasive clearance device has been developed, which measures transcutaneous decay of injected FITC-sinistrin in conscious rodents. The technique was validated against the well-established plasma clearance method in the same mice, but on consecutive days, using only models of uninephrectomy and polycystic kidney disease. We aimed to validate this widely used technique in the same lean or obese mice, at the same time. Five-week-old male C57BL/6J mice were randomised to a high fat diet (n = 12) or normal diet (n = 11) for 10 weeks. Transcutaneous and plasma clearance of FITC-sinistrin were measured simultaneously in each mouse. In lean mice, there was a positive correlation between transcutaneous and plasma derived GFR (P < .01, R2 = .704), although there was an approximate 40% underestimation by the transcutaneous method (P < .0001). In obese mice, no correlation was observed between transcutaneous and plasma derived GFR, nor elimination half-life which removes any effect of the conversion factor and injected dose. The limits of agreement in a Bland-Altman plot were narrower when we used new conversion factors derived from mice in the current study and, in lean mice, a generic conversion factor which assumes 20% extracellular volume. The non-invasive clearance device may be useful for serial GFR measurements in lean and healthy mice, provided validation studies have been carried out, but its utility in obesity requires further study.

Agreement and Precision Analyses of Various Estimated Glomerular Filtration Rate Formulae in Cancer Patients

The accuracy of the estimated glomerular filtration rate (eGFR) in cancer patients is very important for dose adjustments of anti-malignancy drugs to reduce toxicities and enhance therapeutic outcomes. Therefore, the performance of eGFR equations, including their bias, precision, and accuracy, was explored in patients with varying stages of chronic kidney disease (CKD) who needed anti-cancer drugs. The reference glomerular filtration rate (GFR) was assessed by the 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method in 320 patients and compared with the GFRs estimated by i) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, ii) the unadjusted for body surface area (BSA) CKD-EPI equation, iii) the re-expressed Modification of Diet in Renal Disease (MDRD) study equation with the Thai racial factor, iv) the Thai eGFR equation, developed in CKD patients, v) the 2012 CKD-EPI creatinine-cystatin C, vi) the Cockcroft-Gault formula, and vii) the Janowitz and Williams equations for cancer patients. The mean reference GFR was 60.5 ± 33.4 mL/min/1.73 m2. The bias (mean error) values for the estimated GFR from the CKD-EPI equation, BSA-unadjusted CKD-EPI equation, re-expressed MDRD study equation with the Thai racial factor, and Thai eGFR, 2012 CKD-EPI creatinine-cystatin-C, Cockcroft-Gault, and Janowitz and Williams equations were −2.68, 1.06, −7.70, −8.73, 13.37, 1.43, and 2.03 mL/min, respectively, the precision (standard deviation of bias) values were 6.89, 6.07, 14.02, 11.54, 20.85, 10.58, and 8.74 mL/min, respectively, and the accuracy (root-mean square error) values were 7.38, 6.15, 15.97, 14.16, 24.74, 10.66, and 8.96 mL/min, respectively. In conclusion, the estimated GFR from the BSA-unadjusted CKD-EPI equation demonstrated the least bias along with the highest precision and accuracy. Further studies on the outcomes of anti-cancer drug dose adjustments using this equation versus the current standard equation will be valuable.

Toxicity and toxicokinetics of Amanita exitialis in beagle dogs

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 ± 124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12–48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24–72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. α-Amanitin, β-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12–24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0–2 d urine accounted for more than 90% of the total urine excretion.

Validation of a routine two-sample iohexol plasma clearance assessment of GFR and an evaluation of common endogenous markers in a rat model of CKD.

Endogenous markers of kidney function are insensitive to early declines in glomerular filtration rate (GFR) and in rodent models, validated, practical alternatives are unavailable. In this study, we determined GFR by modeling the plasma clearance of two compounds, iohexol and inulin, and compared the findings to common endogenous markers. All plasma clearance methods of both iohexol and inulin detected a decline in renal function weeks prior to any increase in endogenous marker. Iohexol plasma clearance and inulin plasma clearance had a very high agreement and minimal bias when using 12‐sample models. However, only iohexol could be accurately simplified to a two‐sample, one‐compartment estimation strategy. Following an IV injection of low‐dose iohexol and two timed blood samples at 30 and 90 min, one can accurately approximate a complex 12‐sample strategy of plasma clearance. This method is simple enough to use in routine, longitudinal analysis of larger cohort animal studies.

Iohexol plasma clearance, a simple and reliable method to measure renal function in conscious mice.

In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice. We used two groups of mice: testing and validation, formed by 16 animals (8 male and 8 female) each. Iohexol was injected intravenously into the tail vein (6.47mg), and tail tip blood samples were collected at 1, 3, 7, 10, 15, 35, 55, and 75min. Iohexol plasma clearances were calculated in two ways: (1) two-compartment model (CL2) using all time points and (2) one-compartment model (CL1) using only the last four points. In the testing group, CL1 overestimated the true clearance (CL2). Therefore, CL1 was recalculated applying a correction factor calculated as the ratio between CL2/CL1. The latter was considered as the simplified method. CL2 averaged 223.3 ± 64.3μl/min and CL1 252.4 ± 76.4μl/min, which lead to a CF of 0.89. Comparable results for CL2, CL1, and simplified method were observed in the validation group. Additionally, we demonstrated the capacity of the simplified method to quantitatively assess different degrees of renal function in three mouse models: hyperoxaluric-CKD (87.4 ± 28.3μl/min), heminephrectomized (135-0 ± 50.5μl/min), and obese (399.6 ± 112.1μl/min) mice. We have developed a simple and reliable method to evaluate renal function in conscious mice under diverse clinical conditions. Moreover, the test can be repeated in the same animal, which makes the method useful to examine renal function changes over time.

Measuring and estimating glomerular filtration rate in children.

Glomerular filtration rate (GFR) is the best index for kidney function in health and disease. Knowledge of the GFR is essential for the detection (diagnosis) and monitoring of renal function during disease progression and for ensuring correct medication doses. Inulin clearance (plasma or urine) is currently considered to be the gold standard for measuring GFR, but in clinical practice the measurement of other exogenous filtration markers from the plasma often replaces that of inulin clearance. Different protocols can be used to determine the area under the plasma disappearance curve, and an understanding of these methods is important. GFR can also be estimated by GFR equations (eGFR), which are most often used in clinical practice because they only require a knowledge of the serum creatinine or cystatin C level and demographic information. eGFR equations are easy to use but they do have their limitations, and it is important to know how these equations were derived and in which circumstances they can be used most accurately. The aim of this review is to explain how GFR can be measured using the renal clearance and the plasma clearance method and which eGFR equations can be applied to children, as well as how and when these equations can be used in clinical practice.

Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate.

Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. Data from a nine-sample combined plasma exogenous creatinine-iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5-98.2%; specificity 60-91.3%) or borderline (sensitivity 91.1-96%; specificity 76.5-81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

Measurement of glomerular filtration rate in cats: methods and advantages over routine markers of renal function.

Routinely used markers of renal function in clinical practice include urea and creatinine. However, these are insensitive markers, particularly in the early stages of kidney disease. Measurement of glomerular filtration rate (GFR) is regarded as the most sensitive index of functioning renal mass. It may be useful for feline patients in varying clinical scenarios; for example, where a more accurate measurement of renal function may aid diagnosis, to enable response to therapeutic interventions to be more closely monitored, or to evaluate renal function prior to the use of nephrotoxic or renally cleared drugs. Traditional methods of measuring GFR, such as renal clearance or multisample plasma clearance techniques, are generally impractical for clinical use. Limited sampling and single sample plasma clearance methods using the filtration marker iohexol have been validated in cats. These have the advantages of reduced stress to cats associated with repeated sampling and reduced costs of analysis, and therefore offer greater clinical utility. Attempts to develop an estimated GFR (eGFR) formula similar to that used in human patients have been made in cats, although currently an accurate and reliable formula is not available. This review presents the basis for the theoretical understanding and practical measurement of GFR for any veterinary practitioner wishing to obtain a more accurate and sensitive assessment of renal function than routinely used markers provide. The review draws evidence from peer-reviewed publications, the author's PhD thesis and also clinical experience.

Abstract 9847: Glomerular Filtration Rate in Pediatric Heart Transplant Recipients Can be Measured During Routine Catheterization and is Best Estimated by the Full CKiD Formula

Identification of chronic kidney disease (CKD) after pediatric heart transplantation (PHT) is limited by inaccuracies in creatinine-based estimates of glomerular filtration rate (GFR); iohexol plasma clearance is a proven method of measuring GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol during routine coronary angiography in PHT recipients, and that the recently developed CKiD GFR estimating formula, utilizing serum creatinine and cystatin C, provides a better estimate of GFR than creatinine or cystatin equations alone. We performed a cross-sectional study of PHT recipients, ages 2-18 yrs, undergoing surveillance coronary angiography. GFR was measured by obtaining iohexol levels at 2, 4, and 5 hours post-iohexol infusion for angiography, then calculating area under the curve of iohexol disappearance from plasma. Agreement between measured GFR and multiple GFR estimating equations was assessed with Bland Altman plots, correlation, and % of estimates within +/- 10 and 30% of measured GFR. Of 40 enrolled subjects, 31 had complete GFR data. Median age was 15.0 yrs [IQR 7.6, 16.6], time since HT was 5.9 yrs [2.0, 10.8], height %ile was 26 (7, 48), serum creatinine was 0.7 (0.5, 0.8) mg/dL, cystatin C was 0.83 (0.72, 0.91) mg/L, and measured GFR was 89.5 (78.7-107.0) ml/min/1.73m 2 (mean 93.8, SD22.5). A comparison of measured GFR to estimated GFR is shown in Table 1; the full CKiD formula showed best agreement with measured GFR. Conclusions: 1. We describe a novel modified iohexol plasma clearance method to measure GFR in PHT recipients undergoing coronary angiography. 2. Measured median GFR in this cohort is 89.5 ml/min/1.73m2, suggesting early CKD. 3. The full CKiD formula performs best with respect to bias, accuracy, and correlation.

CDK-EPI equation may be the most proper formula based on creatinine in determining glomerular filtration rate in Chinese patients with chronic kidney disease

To compare the performance of the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation, the 24-h creatinine clearance rate (24hCCr), Cockroft-Gault (C-G) formula, the abbreviated Modification of Diet in Renal Disease (aMDRD) equation, the modified Modification of Diet in Renal Disease (mMDRD) equation in determining glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and detect the most proper method to measure GFR in clinical practice. One hundred and fifty-four patients with CKD were enrolled in the present study. (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance method measured by dual plasma sampling method (rGFR) was considered as the reference standard. GFR was estimated simultaneously using five methods: (1) CDK-EPI equation (eGFR1); (2) 24hCCr (eGFR2); (3) C-G formula (eGFR3); (4) abbreviated MDRD equation (eGFR4); (5) mMDRD equation (eGFR5). The comparison of correlation, regression, bias, precision, accuracy, limit of agreement, and receiver-operating characteristics (ROC) for detecting CKD (with a GFR cutoff of 60 mL min(-1) 1.73 m(-2)) among the methods was analyzed to identify the most suitable method. All the equations correlated well with rGFR, and the correlation coefficient of CDK-EPI equation was the highest (reGFR1 = 0.922, P < 0.001). The Bland-Altman analysis showed that the limit of agreement for CDK-EPI equation was -25.5 to 30.3 mL min(-1) 1.73 m(-2), which was the least range among the tested equations. The CDK-EPI equation represented the best capability in precision (14.24 mL min(-1) 1.73 m(-2)). The ROC curve showed the best performance in detecting CKD. The accuracy within ±30 % of CDK-EPI equation, 24hCCr, and mMDRD equation was 72.08, 69.48, and 70.13 %, respectively, and no statistical significant difference was found (P > 0.05). However, CDK-EPI equation had the highest accuracy when compared with the other two equations (P < 0.05). And its performance on bias showed no statistically significant difference compared with other four equations. Although its bias and accuracy did not overmatch the other four equations in our patient group, the CDK-EPI equation outperformed the other equations based on creatinine in correlation, precision, limit of agreement, and detecting CKD, and it is very simple, time-saving, and cost-effective. So we recommend intensely that the CDK-EPI equation is the most suitable method in determining GFR in Chinese patients with CKD and can be applied generally in clinical practice.

Monitoring renal function during chemotherapy

Renal function is monitored during chemotherapy because chemotherapeutic drugs are excreted by the kidneys and are potentially nephrotoxic. Doses are adjusted according to the glomerular filtration rate (GFR), i.e. the more reduced the GFR, the lower the treatment dose. Plasma clearance of (51)Cr-EDTA is a reliable indicator of GFR before and during treatment with potentially nephrotoxic drugs, but its measurement is costly. GFR can also be estimated using an algorithm that converts plasma creatinine concentration to GFR, e.g. the MDRD equation. The aim of this investigation was to evaluate the reliability of estimated GFR (eGFR) in detecting changes in GFR as assessed by the MDRD equation in cancer patients treated with nephrotoxic chemotherapeutic drugs. We included all patients from the Department of Oncology undergoing chemotherapy who were referred to the Department of Nuclear Medicine for measurement of GFR by the (51)Cr-EDTA plasma clearance technique at least four times during the study period of 12 months. The eGFR was calculated from plasma creatinine concentration and the MDRD formula. GFR was determined by the (51)Cr-EDTA plasma clearance method. In 48 patients with a mean age of 47 years, GFR decreased from 86 to 73 ml/min/1.73 m(2) (mean values, p < 0.002) from the first to the last measurement, whereas plasma creatinine concentration and eGFR remained unchanged. In 13 patients (27 %) the finding of a decreased GFR led to adjustment of the dose of the chemotherapy drug. Eight of the 13 patients with decreased GFR also had a reduced eGFR but five patients had a normal eGFR. These five patients would have been treated with the nephrotoxic drug at a dose that was too high. Neither creatinine plasma concentration nor eGFR (MDRD) can be recommended as a replacement for measurement of GFR with the (51)Cr-EDTA plasma clearance method in patients treated with nephrotoxic cytostatic drugs.

Comparison of glomerular filtration rate estimated by plasma clearance method with modification of diet in renal disease prediction equation and Gates method

Glomerular filtration rate (GFR) prediction equations are widely used in clinical practice for quick assessment of kidney function. Gates method using radionuclide technique is an alternative to prediction equations for quick assessment of GFR. Aim of the study was to compare Gates method and modification of diet in renal disease (MDRD) equation in a sizeable patient population with wide range of renal function to evaluate their clinical utility. GFR was estimated in 897 subjects with wide range of renal function by gates method, and MDRD equation and results were compared against measured GFR. Subjects were divided in to 4 groups (0-30 ml, 31-60 ml, 61-90 ml, >90 ml) on the basis of measured GFR and comparison between two methods done through linear regression analysis. Analysis of R2 indicated that 56% of the interindividual variability for Gates GFR was in accordance to variation in measured GFR, in the GFR range of (0-30 ml), this value dropped to 39% in the GFR range of 31-60 ml, 40% in the GFR range of 61-90 ml, 26.4% in the GFR range of >90 ml, the corresponding figure for MDRD GFR were 47.9%, 31.1%, 17.6% and 16.1%, respectively. Gates method is more precise for GFR estimation at all levels of renal function.

Renal function evaluation in an integrative cardio‐renal pharmacology model using Culex Empis® automated drug infusion system and radio telemetry

Recently we showed utility of a novel integrative pharmacology system (CUlex TElemetry: CUTE) that allows simultaneous evaluation of CNS/CV/Renal functions with automated blood sampling in the same rat. To evaluate potential risk of drug‐induced renal and cardiac dysfunction, or their bidirectional effects, a new procedure was developed for simultaneous estimation of heart and global renal function. Briefly, inulin‐FITC (2.5 mg/mL) and p‐aminohippuric acid (PAH; 40 mg/mL) were continuously co‐administered (i.v., 0.5 mL/hour) in conscious, unrestrained Han Wistar rats using Empis® automated drug infusion system combined with CUTE. Steady state was reached after 60 min, and 11 blood samples were collected over the next 3 days. Plasma clearance of inulin and PAH were determined using Fick's principle (renal clearance = infusion rate/plasma level). There were no significant differences in estimated glomerular filtration rate (eGFR) between plasma clearance (0.95 ± 0.05) vs. reference urinary clearance method (1.07 ± 0.14 mL/min/100g BW). Mean blood pressure (102.6 ± 3.54 mmHg) and heart rate (422.9 ± 8.26 bpm) were not altered by infusion of markers for 3 days. This new approach allows simple, rapid and reproducible evaluation of renal function with respect to traditional procedures, making it a useful model for preclinical cardio‐renal safety assessment.