99mTc-DTPA Clearance Research Articles

Effects of Empagliflozin in Type 2 Diabetes With and Without Chronic Kidney Disease and Nondiabetic Chronic Kidney Disease: Protocol for 3 Crossover Randomized Controlled Trials (SiRENA Project).

Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) have revolutionized the treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), reducing the risk of cardiovascular and renal end points by up to 40%. The underlying mechanisms are not fully understood. The study aims to examine the effects of empagliflozin versus placebo on renal hemodynamics, sodium balance, vascular function, and markers of the innate immune system in patients with DM2, DM2 and CKD, and nondiabetic CKD. We conducted 3 double-blind, crossover, randomized controlled trials, each with identical study protocols but different study populations. We included patients with DM2 and preserved kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m2), DM2 and CKD, and nondiabetic CKD (both with estimated glomerular filtration rate 20-60 mL/min/1.73 m2). Each participant was randomly assigned to 4 weeks of treatment with either 10 mg of empagliflozin once daily or a matching placebo. After a wash-out period of at least 2 weeks, participants were crossed over to the opposite treatment. End points were measured at the end of each treatment period. The primary end point was renal blood flow measured with 82Rubidium positron emission tomography-computed tomography (82Rb-PET/CT). Secondary end points include glomerular filtration rate measured with 99mTechnetium-diethylene-triamine-pentaacetate (99mTc-DTPA) clearance, vascular function assessed by forearm venous occlusion strain gauge plethysmography, measurements of the nitric oxide (NO) system, water and sodium excretion, body composition measurements, and markers of the complement immune system. Recruitment began in April 2021 and was completed in September 2022. Examinations were completed by December 2022. In total, 49 participants completed the project: 16 participants in the DM2 and preserved kidney function study, 17 participants in the DM2 and CKD study, and 16 participants in the nondiabetic CKD study. Data analysis is ongoing. Results are yet to be published. This paper describes the rationale, design, and methods used in a project consisting of 3 double-blind, crossover, randomized controlled trials examining the effects of empagliflozin versus placebo in patients with DM2 with and without CKD and patients with nondiabetic CKD, respectively. EU Clinical Trials Register 2019-004303-12; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004303-12, EU Clinical Trials Register 2019-004447-80; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004447-80, EU Clinical Trials Register 2019-004467-50; https://www.clinicaltrialsregister.eu/ctr-search/search?query=and+2019-004467-50. DERR1-10.2196/56067.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults

Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. Cross-sectional diagnostic test substudy of a randomized clinical trial. Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April2021. Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, β-trace protein (BTP) and/or β2-microglobulin (B2M). The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). Registered at ClinicalTrials.gov with registration number NCT03741283. Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as β-trace protein and β2-microglobulin did not further improve accuracy.

Comparison of glomerular filtration rate estimating equations in Indian geriatric patients with cancer.

e24025 Background: Accurate estimation of glomerular filtration rate (eGFR) is essential for dose calculation of certain anticancer drugs. It is particularly important in older cancer patients because of age-related compromise in renal function. 99mTc-DTPA plasma clearance for GFR measurement poses practical difficulties in the elderly and is expensive. Therefore, we investigated the predictive accuracy of eight commonly used eGFR equations against 99mTc-DTPA plasma clearance as the gold standard in Indian geriatric oncology population. Methods: A cross-sectional study was conducted in the geriatric oncology clinic of Tata Memorial Hospital, India, from June 2021 to November 2022. Age, sex, weight, BUN and serum creatinine were obtained from the hospital records. Serum cystatin C was estimated using sandwich ELISA (Sigma, Germany). GFR was estimated using Cockcroft-Gault (CG); 6 variable MDRD; 4 variable MDRD; CKD-EPI creatinine; CKD-EPI cystatin; CKD-EPI creatinine-cystatin; BIS 1; and BIS 2 equations. GFR was also measured by 99mTc-DTPA plasma technique (Gates’ method). The agreement between different eGFR methods and the measured GFR was analyzed using Bland-Altman test. Results: Out of 311 enrolled patients, 276 patients having full covariate data required for estimation of eGFR by all eight equations were included in the analysis. Majority were males (N = 214). Median age (range) of the patients was 68 (60 – 88) years. Median of measured GFR using 99mTc-DTPA was 71 (17 – 141) ml/min. The performance i.e., bias and 95% Limit of Agreement (LoA) of eGFR equations against measured GFR is shown in table 1. Overall, the BIS 2 equation with least bias of 0.854 and narrowest 95% LoA (-31.23 to 32.94) had the highest agreement with ‘gold standard’. In fact, BIS 2 performed consistently well across age (60-70, 71-80, 81-90) and BMI (≤18.5, 18.6-24.9, ≥25) groups (data not shown). BIS 2 was followed by CKD-EPIcr-cys and CKD-EPIcys with best estimates of bias and 95% LoA (Table 1). Interestingly, all three equations have cystatin C as a covariate. 4vMDRD had the highest bias (-24.08) and least agreement with DTPA (-86.52 – 38.36). Post hoc analysis showed that 59/115 (51.3%) patients who were cisplatin-ineligible (GFR < 60) based on CG were cisplatin-eligible based on BIS 2, while 19/161 (11.8%) patients who were cisplatin-eligible based on CG were actually ineligible as per BIS 2. Conclusions: Equations derived using cystatin C in general, and BIS 2 in particular, have highest predictive accuracy for GFR estimation in older cancer patients. [Table: see text]

Validation of the EKFC equation for glomerular filtration rate estimation and comparison with the Asian-modified CKD-EPI equation in Chinese chronic kidney disease patients in an external study

Objectives The aim of this study is to determine whether new European Kidney Function Consortium (EKFC) equation is more applicable than Asian-modified CKD-EPI equation in clinical practice, having a higher accuracy in estimating GFR in our external CKD population. Methods We calculated estimated GFREKFC and GFRCKD-EPI independently using the EKFC and Asian-modified CKD-EPI formulas, respectively. The clinical diagnostic performance of the two equations was assessed and compared by median bias, precision, accuracy (P 30) and so on, using 99mTc-DTPA dual plasma sample clearance method as a reference method for GFR measurement (mGFR). The equation that met the following targets was superior: (1) median bias within ± 3 mL/min/1.73 m2; (2) P 30 > 75%; and (3) better precision and 95% limits of agreement in Bland–Altman analysis. Results Totally, 160 CKD patients were recruited in our external cohort. GFREKFC was highly related to mGFR, with a regression equation of GFREKFC=mGFR × 0.87 + 5.27. Compared with the Asian-modified CKD-EPI equation, EKFC equation demonstrated a wider median bias (–1.64 vs. 0.84 mL/min/1.73 m2, p < 0.01) that was within 3 mL/min/1.73 m2 and not clinically meaningful. Furthermore, the precision (12.69 vs. 12.72 mL/min/1.73 m2, p = 0.42), 95% limits of agreement in Bland–Altman analysis (42.4 vs. 44.4 mL/min/1.73 m2) and incorrect reclassification index of the two target equations were almost identical. Although, EKFC equation had a slightly better P 30 (80.0% vs. 74.4%, p = 0.01). Conclusions The overall performance of EKFC equation is acceptable. There is no clinically meaningful difference in the performance of the Asian-modified CKD-EPI and EKFC equations within the limits imposed by the small sample size.

Estimated glomerular filtration rate based on creatinine, cystatin C, β-trace protein and β2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, β-trace protein (BTP) and β2 microglobulin (B2M) among patients undergoing major amputation. This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P= 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P =0.006) and eGFRcre[2021] (+6.3 mL/min, P =0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P> 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline

SummaryIntrathecal administration enables central nervous system delivery of drugs that do not bypass the blood-brain barrier. Systemic administration of hypertonic saline (HTS) enhances delivery of intrathecal therapeutics into the neuropil, but its effect on solute clearance from the brain remains unknown. Here, we developed a dynamic in vivo single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging platform to study the effects of HTS on whole-body distribution of the radiolabeled tracer 99mTc-diethylenetriaminepentaacetic acid (DTPA) administered through intracisternal, intrastriatal, or intravenous route in anesthetized rats. Co-administration of systemic HTS increased intracranial exposure to intracisternal 99mTc-DTPA by ∼80% during imaging. In contrast, HTS had minimal effects on brain clearance of intrastriatal 99mTc-DTPA. In sum, SPECT/CT imaging presents a valuable approach to study glymphatic drug delivery. Using this methodology, we show that systemic HTS increases intracranial availability of cerebrospinal fluid-administered tracer, but has marginal effects on brain clearance, thus substantiating a simple, yet effective strategy for enhancing intrathecal drug delivery to the brain.

Measurement and Estimation of Glomerular Filtration Rate in Children With Neurogenic Bladder: A Prospective Study

ObjectiveTo evaluate the performance of different equations used to estimate glomerular filtration rate (GFR) in children with neurogenic bladder (NB). MethodsThe GFR measured with the technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) dual-plasma sample clearance method was defined as the true GFR (tGFR). The Chronic Kidney Disease in Children (CKiD) equation for serum creatinine (Scr) and/or cystatin C (Cys C) was used for GFR calculation. Estimated GFR (eGFR) using CKiDScr, CKiDCys C, and CKiDScr+Cys C equations was compared with tGFR in children with NB. ResultsIn total, 458 children with NB were prospectively enrolled in this study. The mean tGFR was 73.84 ± 18.54 ml/min/1.73 m2, mean eGFRScr was 77.94 ± 18.38 ml/min/1.73 m2, mean eGFRCys C was 74.20 ± 17.64 ml/min/1.73 m2, and mean eGFRScr+Cys C was 75.70 ± 18.07 ml/min/1.73 m2. The correlation between the Scr-based equation and 99mTc-DTPA clearance method was low (r = 0.648). The Cys C-based equations exhibited the strongest correlations: CKiDCys C (r=0.891) and CKiDScr+Cys C (r = 0.879). The overall prevalence of chronic kidney disease (CKD) was 20.7%, 19.7%, 17.5%, and 12.4% according to tGFR, eGFRCys C, eGFRCys C+Scr and eGFRScr, respectively. The area under the curve (AUC) for the Receiver operating characteristic (ROC) curve of the CKiDCys C equation was the highest (AUCCKiDcys = 0.956). ConclusionThe Cys C-based CKiD equation was the most accurate for estimating GFR compared with 99mTc-DTPA clearance method in children with NB. The CKiDScr equation overestimated the GFR. The CKiDCys C equation can be used to detect initial stages of CKD in children with NB.

Measurement of glomerular filtration rate and its current status in African countries GFR measurement and its status in Africa

Glomerular filtration rate (GFR) is usually estimated rather than measured as this only requires measurement of an endogenous filtration marker. In certain clinical settings a more accurate measure of GFR is essential. The most commonly used endogenous filtration marker is creatinine. Exogenous filtration markers include nonradiopharmaceuticals such as inulin, iohexol and unlabelled iothalamate, or radiopharmaceuticals such as 51Crethylenediaminetetraacetic acid (51Cr-EDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). Inulin is considered an ideal filtration marker but the clearance of iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol have all been shown to have sufficient accuracy for measuring GFR. For radiopharmaceuticals, a well counter is required to measure the amount of activity in patient samples. Iohexol or unlabelled iothalamate require samples to be measured using high performance liquid chromatography with ultraviolet detection (HPLC-UV), liquid chromatography-tandem mass spectrometry (LC-MS/MS) or x-ray fluorescence (XRF). Due to the practical challenges of measuring urinary clearance, measurement of GFR in clinical settings is almost exclusively based on plasma clearance of a filtration marker. This can follow a long-established approach based on the ratio of the tracer administered to the area under the plasma concentration curve. Alternatively, a single plasma sample giving an apparent volume of distribution at a given time point can be used to accurately measure GFR. While techniques exist for the measurement of GFR in a number of African countries, preliminary evidence suggests that facilities are very limited. There is a need for support for both equipment and training to establish GFR measurement facilities in several centres on the continent. Keywords: measured glomerular filtration rate;, mGFR;, Africa

Age-specific normal reference ranges for 99mTc-DTPA glomerular filtration rate to use with two-sample slope-intercept method and Jodal Brochner-Mortensen correction.

Glomerular filtration rate (GFR) varies with age, the calculation method, and the correction factor for slope-intercept overestimation. Hence, any normal reference range accompanying the results should be suitably adapted to the method used. For Nuclear Medicine Departments using a two-sample slope-intercept method, the lack of appropriate age-specific normal reference range has been a hindrance to adopting the recently updated Jodal Brochner-Mortensen (JBM) correction over other older and more widely used methods. A retrospective analysis of the routine GFR calculation and clinical reports generated locally from 2006 to 2020 was carried out. GFR was calculated with 99mTc-DTPA plasma clearance using a two-sample slope-intercept method with JBM correction. Age-specific normal range equations were developed from normal healthy subjects. Published normal reference ranges were modified with appropriate correction reversal and compared with the locally developed reference ranges. Age-specific normal GFR reference ranges for 99mTc-DTPA with slope-intercept method and JBM correction were developed and validated with current literature. Normal reference range (Mean ± 2SD) for Normalised GFR (ml min-1 (1.73m2)-1) within 95% confidence limits suitable for use with JBM correction is 100.6 ± 35.2 for children above 2years and 102.9 - 0.00629 × (Age)2 ± 19.4 for adults. Availability of age-specific normal GFR reference ranges applicable to the target population and appropriately tailored to the calculation method and correction factor enables Nuclear Medicine Departments to update their calculation methods in line with the current literature and also facilitates accurate reporting and evaluation of the calculated GFR results.

Technetium‐99m‐MAG3 and technetium‐99m‐DTPA: Renal clearance measured by the constant infusion technique – Old news?

Accurate, precise and straightforward methods for measuring glomerular filtration rate (GFR) and/or renal plasma flow (RPF) are still in demand today. The time-consuming constant infusion technique (CIT) is the gold standard and preferred for research, whereas the simple, but less precise, single injection technique (SIT) is used in clinical settings. This study investigated the use of 99m Tc-DTPA and 99m Tc-MAG3 by CIT as a measure of renal function. We developed and evaluated a model to balance the primer dose and infusion rate in an attempt to obtain plasma steady state as quickly as possible. 14healthy subjects received 99m Tc-DTPA and 6hypertensive patients received 99m Tc-MAG3 in a standardized protocol. All participants had an eGFR above 60 ml/min and none had fluid retention. An intravenous primer injection of the relevant tracer was followed by a sustained infusion over 4.5h with the same radiopharmaceutical. Blood and urine samples were collected at fixed intervals. 99m Tc-DTPA clearance reached steady state after 210min (plasma clearance 78±18ml/min, urine clearance 110±28ml/min), whereas 99m Tc-MAG3 clearance achieved steady state after 150min (plasma clearance 212±56ml/min, urine clearance 233±59ml/min). Constant infusion technique with fixed primer and infusion rate using 99m Tc-MAG3 is feasible for research purposes. The longer time for reaching plasma steady state using 99m Tc-DTPA makes CIT with this tracer less optimal. If the primer/sustained balance can be optimized, for example using a priori SIT information, 99m Tc-DTPA as tracer for CIT may also be feasible.

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.

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at 6 academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m2 at a 5% significance level. Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/minute/1.73 m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1 year after surgery. The change in mGFR 1 year after surgery was -6.6 ml/minute/1.73 m2 in the hypothermia group and -7.8 ml/minute/1.73 m2 in the control group (mean difference 1.2 ml/minute/1.73 m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 ml/minute/1.73 m2; mean difference 0.5 ml/minute/1.73 m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

TA COMPARISON OF THE CREATININE CLEARANCE BY GFR ESTIMATING EQUATIONS WITH MEASURED GFR BY ISOTOPE SCAN IN VOLUNTARY LIVING KIDNEY DONOR

Background: Glomerular filtration rate (GFR) is essential for renal function evaluation. The need for estimating GFR stems from the shortcomings of interpreting plasma creatinine alone, the cost and complexities of determining a gold standard GFR with either inulin or radionuclides like iothalamate, and the inaccuracies associated with the measurement of a 24 h urine creatinine clearance. It is of special concern in Voluntary Kidney Donor(VKD) in living donor transplantation. Equations like Cockcroft- Gault formula (CGF), Modified Diet in Renal Disease (MDRD) and the Chronic kidney disease- Epidemiology Collaboration equation (CKD-EPI) are useful in estimating GFR. This study is to validate the different GFR estimating equations, and their correlation with measured GFR by nuclear Isotope scan in VKD. Methods: We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 814 healthy adult (=>18yrs) individuals. Using mGFR as the gold standard, we evaluated the efficiency of three different GFR estimation equations (CGF, MDRD and CKD-EPI) and calculated their precision and correlation. Result: In our population, the mean mGFR was 81.46 ± 14.35 mL/min/1.73m2. In correlation analysis, the three equations have significant linear correlation with mGFR (p<0.01), and the linear regression demonstrated moderate explanatory capacity of eGFR produced by CKD-EPI (R2 = 0.22), CGF (R2 = 0.15) and MDRD (R2 = 0.12). The slopes in the Bland-Altman analysis of CGF, MDRD and CKD-EPI are -0.68, -0.41 and -0.18. Intraclass coefficients was highest for CKD-EPI (0.63), followed by CGF (0.51) and MDRD (0.49). Thus, The CGF, MDRD and CKD-EPI formula produced eGFR with strong correlation with mGFR, moderate explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis and high intra-class correlation coefficients. Conclusion: This study concludes significant correlation between measured GFR and the GFR estimating equations: CGF, CKD EPI and MDRD. Of the three, CKD -EPI has the highest precision of GFR prediction in VKD.

Simultaneous glomerular filtration rate determination using inulin, iohexol, and 99mTc-DTPA demonstrates the need for customized measurement protocols

Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and 99mTc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma 99mTc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (<30, 30-59, and≥60 ml/min/1.73m2) and the edema stage using urinary inulin clearance as the gold standard. The mean inulin GFR of the 77 participants was 33 ml/min/1.73m2. Delay of both the initial and the final samples in plasma iohexol protocols yielded the highest accuracy in the setting of low GFR (<30 ml/min/1.73m2). Early initial and final samples yielded the highest accuracy in the setting of high GFRs (≥60 ml/min/1.73m2). No sampling strategy was accurate in edematous patients. Thus, our study demonstrates that customization of GFR protocols according to the anticipated level of GFR are required to optimize protocol accuracy.

P0656FULL AGE SPECTRUM EQUATION IN THE ESTIMATION OF GLOMERULAR FILTRATION RATE IN RUSSIAN ADULT PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Glomerular filtration rate (GFR) is the most important and accurate parameter of kidney function in the course of chronic kidney disease (CKD). Renal or plasma inulin, diethylenetriaminepentaacetate (DTPA), ethylenediaminetetraacetate (EDTA), radiocontrast agents (iohexol, iothalamate) and some other substances clearances are the reference methods for determining GFR. However, these methods cannot be applied routinely because of the inconvenience. Several available methods have been developed to estimate GFR in a simpler manner and at low costs. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is widely used to evaluate the GFR in practice. However, this equation is not accurate for the full age spectrum. In 2016, the new equation, full age spectrum equation, based on the serum creatinine (FAScr), was developed and can be applicable to all ages. However, data on the benefits of using the FAScr-method in different populations are contradictory. In particular, it is unclear whether the FAScr provides any advantages over the CKD-EPI method in adults. In this regards, we attempted to compare data obtained FAScr method with results some non-reference and reference methods in adult Russian population. Method We examined 120 Caucasian patients (M:F - 52:68; age 18-76 year) with CKD 1 - 5 stages. Patients with nephrotic syndrome and congestive heart failure were excluded. GFR (reference method) measured by plasma clearance of 99mTc-DTPA (CDTPA). CDTPA determined by one- compartment model 2-4 h method using a Chantler-Barratt linear correction. Estimation GFRs (eGFR) were established by Cockcroft-Gault creatinine clearance (CG), CKD-EPI (creatinine), FAScr and Modification of Diet in Renal Disease (MDRD) methods. Also, renal creatinine clearance (Ccr; UV/P method) was measured. Only GFRs values corrected on 1.73 m2 body surface area had been use. Results The values of GFR (Mean(SEM)) are: CDTPA 67.0(2.46); FAS 69.7(2.50); CKD-EPI 64.3(2.54); MDRD 60.9(2.62); CG 77.6(3.31); Ccr 85.2(3.40), мл/мин/1.73 m2. MDRD was significantly lower (paired Student t-test with correction on multiply comparison by Benjamini-Hochberg method) than CDTPA (P=0.0024), CG (P=0.0001) or Ccr (P&amp;lt;0.0001) were significantly higher. The bias (CDTPA minus non reference GFR) were: FAS -2.67(1.71); CKD-EPI 2.72(1.58); MDRD 6.12(1.78); CG -10.57(2.51); Ccr -18.22(2.26), ml/min. All biases are significantly differ between themselves (P from 0.00064 to &amp;lt;0.000001). The percentage of P30 of the FAS 81.6(3.5) was not significant differ from P30 of CKD-EPI (78.3(3.8); P=0.524) or MDRD (71.7(4.1); P=0.071). However, P30 of CG (67.5(4.3),%; P=0.01) or Ccr (54.2(5.42),%; P&amp;lt;0,001) were significant lower, than P30 of FAS. There were significant comparable direct correlations between CDTPA and FAS (r=0.764), CKD-EPI (r=0.801), MDRD (r=0.756), CG (r=0.656), Ccr (r=0.749); P&amp;lt;0.00001 in all cases. Conclusion In adult Russian population FAScr-method of GFR estimation had not any advantage over CKD-EPIcr-method.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16–226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) –6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.

The variation of selective uNGAL levels after robot-assisted partial nephrectomy: Early results of a prospective single center study.

Acute kidney injury (AKI) secondary to nephron-sparing surgery represents a significant problem in order to preserve renal function. Since serum creatinine alone underestimates the early detection of AKI several biomarker have been investigated. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is considered a good biomarker for AKI. We report our experience in 28 patients affected by localized renal cell carcinoma and submitted to robot-assisted partial nephrectomy (RAPN). In each patient selective urinary NGAL levels were dosed before surgery, then 2 and 48 hours after the procedure, through a ureteral catheter inserted into the excretory axis of the operated kidney. Moreover, we evaluated split renal function of the preserved renal parenchyma by a 99mTC-DTPA renal scintigraphy, performed before surgery and three months later. AKI was diagnosed, according to internationally criteria, in 3 patients (10.7%). The baseline selective urinary NGAL level was 20.02 ng/ml. This level significantly increased after surgery with a selective urinary NGAL level that reached 56.36 ng/ml (p < 0.0001). Moreover, a significant reduction in 99mTC-DTPA clearance of the operated kidneys after three months was detected (p < 0.0001). Selective urinary NGAL assay represent a sensitive biomarker of acute kidney injury after robotic nephron sparing surgery, capable of predicting the functional outcome of the operated kidney.

Evaluation of the Royal Free Hospital Cirrhosis Glomerular Filtration Rate Formula in Hispanic Patients with Cirrhosis: An External Validation

Glomerular filtration rate (GFR) measurement in patients with liver cirrhosis (LC) is the ideal method for adequate evaluation of kidney function. However, it is invasive, costly, and not widely accessible. Moreover, GFR estimation in patients with cirrhosis has been inaccurate. The aim of the present study was to evaluate and validate the recently described Royal Free Hospital (RFH) formula in a Hispanic cohort of patients with LC and compare it with other formulas, including the CKD-EPI cystatin C equation. GFR was measured through the renal clearance of Tc-99m DTPA; it was cross-sectionally evaluated and compared with GFRs that were estimated utilizing the following formulas: RFH, Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease-6, CKD-EPI cystatin C, CKD-EPI Creatinine, and CKD-EPI Cystatin C-Creatinine. We included 76 patients (53% women). The mean measured GFR in the entire cohort was 64 ml/min/1.73m2; 54% of the patients had a GFR < 60 ml/min/1.73 m2 at the time of evaluation. The RFH formula and the CKD-EPI cystatin C formula showed the best performance, with a p30 of 62% and 59%, respectively. All formulas performed poorly when GFR was < 60 ml/min/1.73 m2. The RFH formula showed a better performance than the other formulas based on serum creatinine in a Hispanic population with LC. There was no difference in performance between the RFH formula and the CKD-EPI cystatin C formula.

Validity of current equations to estimated glomerular filtration rate in geriatric population

Background Despite the estimation of glomerular filtration rate (GFR) being the best index of kidney function, and estimated glomerular filtration rate (eGFR) being limited by differences in creatinine generation among different age groups, the data regarding the accuracy of serum creatinine-based formulae on the geriatric population is still scarce. Aim Our aim is to investigate the accuracy of the eGFR equations to predict renal function in geriatric population versus the measurement of true GFR by diethylenetriaminepentaacetic acid (99mTc-DTPA). Patients and methods The study included 160 elderly persons, with 93 (58%) females. All persons were from Minia Governorate, Egypt. GFR was estimated using Modification of Diet in Renal Disease, abbreviated Modification of Diet in Renal Disease, Walser, Nankivell, Cockcroft–Gault, Mayo Clinic, and Chronic Kidney Disease Epidemiology Collaboration. The true GFR was determined for all participants with 99mTc-DTPA. Results All the seven eGFR estimations correlated with 99mTc-DTPA clearance (P Conclusion In the geriatric population, the overall performance of these seven prediction equations did not give a precise assessment of kidney function, that is, all analyzed formulae lacked the precision to estimate true GFR.