Plasma Clearance Of Iohexol Research Articles

Measured glomerular filtration rate predicts liver related deaths better than estimated glomerular filtration rate in advanced chronic liver disease

Background & aimsRenal dysfunction is prevalent in advanced chronic liver disease (aCLD) and is associated to liver-related death (LRD). This makes a reliable evaluation of renal function (RF) a crucial aspect. RF can be estimated by formulas or measured by gold standard method. Estimated RF is not reliable in aCLD. However, there is a lack of information on the reliability of formulas in the prediction of LRD. MethodsWe analysed a cohort of patients with aCLD in whom RF was measured by the plasma clearance of iohexol (mGFR) and estimated (eGFR) by formulas: MDRD, CKD-EPI, Royal Free Hospital (RFHC), GRAIL and Mindikoglu-eGFR. LRD was defined as death from hepatic causes. Multivariable analysis was used to evaluate association of mGFR or eGFR with LRD. Results161 patients were evaluated, with median follow-up of 28 months, 58 died from LRD. In overall group mGFR (OR 0.99; p = 0.022) and formulas: CKD-EPI (OR 0.98; p = 0.044), GRAIL (OR 0.98; p = 0.038) was associated with LRD. In patients with normal creatinine levels (≤ 1.1 mg/dL), mGFR (OR 0.99; p = 0.031) was whereas any formula was not associated with LRD. ConclusionseGFR appears as an unreliable method for predicting LRDs in aCLD, especially in those with lower creatinine levels. By contrast, mGFR seems to be a superior predictor.

Iohexol Plasma Clearance Measurement Protocol Standardization: A Consensus of the European Kidney Function Consortium

Iohexol Plasma Clearance Measurement Protocol Standardization: A Consensus of the European Kidney Function Consortium

Measured GFR Implemented in a US Clinical Practice: Comparing 4-Hour and 10-Hour Plasma Iohexol Clearance

Measured GFR Implemented in a US Clinical Practice: Comparing 4-Hour and 10-Hour Plasma Iohexol Clearance

Development and Validation of an Accurate Creatinine-Based Equation to Estimate Glomerular Filtration Rate for the Adult Indian Population: Design and Methods

Background Existing creatinine-based equations to estimate glomerular filtration rate (GFR), developed primarily in populations of European and African American ancestry, do not accurately reflect the GFR in the Indian population due to differences in body composition, diet, and other factors. This manuscript describes the rationale and methodology for developing a creatinine-based equation for more accurate GFR estimation in Indian subjects. Materials and Methods This cross-sectional study will be conducted in India’s two geographically and demographically diverse locations: Chandigarh (north) and Puducherry (south). Participants will include a representative sample from the general population and subjects with chronic kidney disease (CKD), with the latter being recruited from outpatient clinics. A total of 1558 subjects will be enrolled in the discovery and cross-validation cohort and 620 subjects in the external validation cohort. The reference standard for measured GFR (mGFR) will be the plasma clearance of iohexol. Stepwise multiple regression on log-transformed data will determine a set of variables that jointly predict mGFR and identify factors influencing mGFR and estimated (eGFR) in the study population. This study will also explore the performance of mGFR by iohexol measurement from dried blood spots against mGFR from plasma clearance of iohexol. Conclusion Developing a more reliable and accurate creatinine-based GFR estimating equation will improve CKD diagnosis, classification, and management. The findings will have substantial implications for CKD research in India and other regions with similar populations.

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.

A physiological model for iohexol plasma clearance supporting diagnostics of kidney function

BackgroundThere are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol. MethodsA mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period. ResultsThe mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately. ConclusionsThe physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.

Creatinine-based formulas are not ideal to estimate glomerular filtration rate in selected pediatric patients: data from a tertiary pediatric nephrology center.

Evaluating glomerular filtration rate (GFR) remains challenging in pediatrics; new formulas were developed to increase performance of GFR estimation (eGFR). We aimed to evaluate the recently published formulas as applied to another pediatric population. A retrospective study was conducted in a cohort of 307 patients with a "kidney risk" (mean age 12.1 ± 4.5 years, sex ratio 1/1) assessed in a tertiary pediatric nephrology center and a mean measured GFR (mGFR) using plasma iohexol clearance of 85.5 ± 25.3 mL/min/1.73 m2; creatinine levels were measured by IDMS-standardized enzymatic method and cystatin C by immunonephelometry. The following eGFRs were calculated: Schwartz2009, Schwartz-Lyon, CKiDU25creat, and EKFC for eGFR using creatinine (eGFR-creat), CKiDU25cys and FAScys for eGFR using cystatin (eGFR-cys) as well as combined SchwartzCreat-Cys, average (CKiDU25creat-CKiDU25cys), and average (EKFC-FAScys) for eGFR using both biomarkers. The performance of the different formulas was evaluated compared to mGFR by absolute bias measurement and accuracy (p10%, p30%). Results are expressed as mean ± SD. Creatinine-based formulas and especially the new CKiDU25 and EKFC overestimate GFR, even in children with normal kidney function. However, the bias is constant with these two formulas whatever the age group or gender, contrary to the previously published formulas. In contrast, cystatin C-based equations and combined formulas showed good performance in all age groups and all medical conditions with an acceptable bias and p30%. In our pediatric population, the performance of all creatinine-based formulas is inadequate with significant GFR overestimation, mainly in subjects with mGFR > 75 mL/min/1.73 m2. Conversely, cystatin C-based or combined formulas have acceptable performance in patients followed in a tertiary pediatric nephrology unit.

#2575 GFR in onco-nephrology: the innovative use of measured GFR in the management of oncological solitary kidney

Abstract Background and Aims A reliable assessment of renal function in onco-nephrology and especially in oncological solitary kidney (SK) is of paramount importance. Nowadays, the use of estimated GFR is predominant in clinical practice because it is fast, easy and cost-effective. However, eGFR harbours a significant error in comparison to gold standards methods using exogenous molecules such as iohexol or iothalamate (mGFR). Aim of this study was to determine the extent of the error of eGFR compared to the mGFR in onco-nephrological patients with a solitary kidney (SK) after nephrectomy (RN). Method A total consecutive cohort of 200 SK who previous underwent RN for renal cancer was enrolled in a single tertiary institution from 2017 to 2023 to compare the most used eGFR formulas (MDRD, CKD-EPI crea 2012, CKD-EPI 2021 crea, CKD-EPI cyst 2012, CKD-EPI Cyst 2021, CKD-EPI cyst/creat, Cockroft-Gault) with a mGFR method using Iohexol Plasma Clearance. Clinical and laboratory data were reported for each patient. True positives (TP) and False positives, (FP) were classified in CKD stages based on eGFR and mGFR. Comparisons between groups were performed using Wilcoxon ranks sum test for numerical variables and Pearson's Chi square test for categorical ones. Results Overall median age was 67 years (IQR: 56.75), median BMI 24.8 (IQR: 22.8; 27.7), Male: 74.9%,F: 25.1% Diabetes: 10.9% Hypertension: 53.8%, CKD stage I: 3.7%, II: 25.5%, IIIA:28,IIIB: 27.5%, IV: 13.4%, V: 1.74%, mean Creatinine:1,46 mg/dl (1.16-1,84), cystatin: 1.23 (0.95-1.56). Surprisingly, SK cohort harboured a non-negligible errors in each CKD class with a huge discrepancy between the eGFR formulas and the gold standard method (Figs 1 and 2), suggesting the great relevance of mGFR in the clinical decision making algorithm. Conclusion The use of mGFR in nephrectomized patients for RC remains fundamental to avoid misleading evaluations and to perform correct personalized pharmacological therapies.

#1128 Accuracy of shorter iohexol glomerular filtration rate measurement protocols in individuals with preserved kidney function

Abstract Background and Aims Measuring glomerular filtration rate (mGFR) using exogenous tracers is recommended in a number of settings with plasma one-compartment multi-sample protocols (MSP) being the most commonly used and iohexol being the dominant tracer. The accuracy of MSP protocols has mostly been evaluated in the setting of reduced GFR where delayed initial and final samples are recommended. Much less is known about MSPs when GFR is not decreased and the default protocol tends to include initial sampling at 120 minutes and final sampling at 240 minutes post iohexol injection. The objective of this study was to assess the performance of shorter MSPs with earlier initial (60 and 90 minutes) and final (150, 180, and 210 minutes) sampling times in individuals with preserved GFR. Method Participants were recruited from a 4-year prospective, observational study evaluating the cardiovascular, renal, and bone health profile of young adults with Type 1 Diabetes. The reference mGFR was calculated using a plasma iohexol clearance one compartment slope intercept method with 5 samples collected between 120-240 minutes post iohexol injection. Four different combinations of shorter sampling strategies were investigated: 60-150 min, 60-180 min, 90-180 min and 90-210 min. Performance was evaluated using measurements of bias, precision, and accuracy (P2, P5, and mean absolute error). Results Mean age of the 43 participants was 23.9 ± 1.9 yrs with a mean eGFRCKiD-1 of 95.5 ± 15.9 ml/min/1.73 m2 and mean reference mGFR (120-240 min) of 102.3 ± 13.7 ml/min/1.73 m2. All exploratory shorter mGFRs performed well, with median biases less than 1 ml/min/1.73 m2 and mean absolute error less than 1.6 ml/min/1.73 m2. All shorter mGFRs were within 5% of the reference mGFR and the majority were within 2%. Conclusion These results demonstrate that shortening the mGFR procedure in individuals with preserved GFR provided very similar results to the current standard while significantly decreasing procedure time. The cost savings and improved feasibility of these shortened protocols should reduce some of the barriers to more widespread adoption of GFR measurement.

#2422 Iohexol plasma clearance measurement protocol standardization—a consensus of the European Kidney Function Consortium

Abstract Background and Aims International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the adoption of mGFR determination in both clinical and research settings. Method The European Kidney Function Consortium (EKFC) convened an international group of mGFR experts. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using one-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, widely available, and can be assayed at a central laboratory. Other commonly used non-radio labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected as it requires no timed urine collections. A one-compartment model was preferred to a two compartment model as it requires fewer samples. The resulting recommendations were based on published evidence complemented by expert opinion. Results Recommendations include practical advice for patients and health professionals, preparation, administration and safety aspects of iohexol, laboratory analysis, blood sample collection and sample timing for both multiple and single sample protocols, description of the mGFR mathematical calculations as well as implementation strategies (Fig.). EKFC will provide materials such as patient information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation. Conclusion Members of the EKFC have evaluated the evidence and formulated recommendations that include all aspects of iohexol plasma clearance measurement using a one compartment model. *Author list on behalf of the European Kidney Function Consortium (EKFC).

#2888 Measured glomerular filtration rate and risk of adverse outcomes in 6059 patients from the Stockholm CREAtinine Measurements (SCREAM) project

Abstract Background and Aims Evidence on the risks of adverse outcomes associated with glomerular filtration rate (GFR) has been limited to estimated GFR (eGFR), due to limited availability of large-scale data with measured GFR (mGFR). These studies either used creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys), which can be influenced by the non-GFR determinants of creatinine and cystatin C. Here, we aimed to (1) quantify associations between mGFR and the risk of all-cause mortality and kidney failure with replacement therapy (KFRT) and (2) investigate which filtration marker most closely resembled these associations. Method We included 6059 adults referred for single-point plasma iohexol clearance between 2011-2021 in Stockholm, Sweden (SCREAM project), and who had simultaneous measures of creatinine and cystatin C. eGFR was calculated with the CKD-EPI 2012 (eGFRcys) and 2021 (eGFRcr and eGFRcr-cys) equations. Hazard ratios were estimated using Cox regression, adjusting for age, sex, medical history, medications and urinary albumin-to-creatinine ratio (UACR). Results Mean age was 59 years, 40% were women, median mGFR was 66 ml/min/1.73 m2 and median UACR was 1.1 mg/mmol. During median 3.8 years of follow-up, 1961 individuals died and 425 progressed to KFRT. Associations between mGFR and mortality increased linearly for values &amp;lt;90 ml/min/1.73 m2 and were not statistically significant between 90-120 ml/min/1.73 m2 (Figure). Compared with mGFR of 90 ml/min/1.73 m2, hazard ratios for mortality were 1.5 (95% CI 1.3-1.6), 1.7 (1.5-1.8), 2.0 (1.8-2.1) and 2.4 (2.0-2.7) for 60, 45, 30 and 15 ml/min/1.732, respectively (Table). eGFRcr-cys most closely resembled the mortality risk relationships of mGFR. Conversely, eGFRcr had a strong U-shaped pattern with underestimation of risks &amp;lt;90 ml/min/1.73 m2 and overestimation of risks between 90-120 ml/min/1.73 m2; for eGFRcys this pattern was reversed. Associations between mGFR and KFRT were also linear (Figure). Compared with mGFR of 60 ml/min/1.73 m2, hazard ratios for KFRT were 2.1 (1.4-3.0), 6.2 (4.5-8.5), and 32.1 (23.4-44.0) for 45, 30 and 15 ml/min/1.732, respectively (Table). Both mGFR and estimating equations displayed similar monotonic risk associations. Conclusion In the largest study on mGFR and outcomes to date, lower mGFR was linearly associated with an increase in the risks of mortality and KFRT. eGFRcr-cys closely resembled the relationship between mGFR and mortality, whereas eGFRcr under-estimated mortality risk and had a U-shaped association. All estimating equations had similar associations with KFRT risk.

Measurement of Glomerular Filtration Rate in Patients Undergoing Renal Surgery for Cancer: Estimated Glomerular Filtration Rate versus Measured Glomerular Filtration Rate in the Era of Precision Medicine.

In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. This paper delves into the significance of accurately measured glomerular filtration rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional glomerular filtration rate (GFR) estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

DETERMINATION OF DFG IN A BLACK AFRICAN POPULATION WITH CHRONIC KIDNEY DISEASE IN 2023: COMPARISON OF THE PERFORMANCE OF 11 ESTIMATION EQUATIONS

Introduction: Chronic kidney disease is a public health problem. To date, several equations have been proposed for its diagnosis, but these remain relatively approximate. In Africa, in the absence of specific recommendations, these formulas are used with the consequent risk of diagnostic bias, whereas in recent years, studies carried out in Africa have questioned the relevance of the ethno-racial factor used in certain equations in a healthy population. The aim of this study was therefore to evaluate 11 equations currently in use in black African chronic kidney disease patients. Material and Methods: This was an analytical cross-sectional study involving 183 chronically ill renal patients in whom GFR was measured by iohexol plasma clearance used as a reference and estimated by 11 current equations. The performance of the current equations was determined by calculating the median bias, interquartile range and accuracy at P30 in comparison with the reference method. Results: EKFC equations showed the best bias and accuracy at 30%. The 2021 CKD epi equations have not proven their performance in our African population of chronic kidney disease subjects. The use of cystatin as a biomarker added value to each type of equation. Unfortunately, the 30% accuracies of all equations remain below 75% in the chronic kidney disease population. Conclusion: The equation best suited in 2023 to our sick black African population is the EKFC equation and its variants. Although it remains the best-performing, the 30% accuracy remains below 75%.

Estimation of Glomerular Filtration Rate Using the New Ekfc Equation in Healthy and Chronic Kidney Disease Adult Subjects from Sub-Saharan Africa

Introduction: Since the publication of the first equation for estimate creatinine clearance in 1957, several other equations estimating glomerular filtration rate have followed in succession. To date, a new equation has been published by the European Kidney Function Consortium (EKFC) in 2021, which would have the advantage of being adaptable to any type of population. In this study, we aimed to evaluate the performance of this new equation in our black African population of healthy subjects and subjects with chronic kidney disease.&#x0D; Material and Methods: This was a cross-sectional study involving 192 healthy subjects and 183 subjects with chronic kidney disease. Plasma iohexol clearance (mGFR) constituted́ the reference method used to measure glomerular filtration rate and allowed evaluation of all equation variants (EKFC crea, EKFC cys, EKFC crea-cys). Equation performance was studied by calculating the 95% CI bias, the interquartile range (25% percentile, 75% percentile) and the 30% accuracy (P30) compared with the reference method.&#x0D; Results: All EKFC variants in both populations (healthy subjects and chronic kidney disease subjects) had biases below 5 ml/min/1.73 m2. Biases were therefore acceptable. On the other hand, P30s were less good in subjects with chronic kidney disease.&#x0D; Conclusion: Thus, the EKFC equation performs well in the healthy population, but its evaluation in the chronic kidney disease population needs to be strengthened on the basis of larger cohorts.

Assessing the Reliability of Creatinine-Estimated Glomerular Filtration Rate in Living Kidney Donor Candidates: Does it Measure up to the Measured Rate?

Abstract A living donor kidney transplant is the best therapy option for patients with end stage renal disease (ESRD); however, it is associated with an increased risk of ESRD development in the donor. Thorough evaluation of the donor candidate’s kidney function status is essential for the appropriate selection of candidates with minimal risk of post-donation kidney dysfunction. In this study, glomerular filtration rate (GFR) values measured by iohexol plasma clearance (mGFR) and estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) creatinine equations (eGFR), with and without the race factor (2009 and 2021 CKD-Epi equations, respectively), were compared in a cohort of 303 kidney donor candidates. GFR values were analyzed using Bland-Altman plots, linear regression, Mann-Whitney U tests, and p10 and p30 values. Bland-Altman analysis revealed a lack of agreement between the 2009 and 2021 CKD-Epi eGFR and corresponding mGFR values, with both equations showing a negative bias of 10 – 11 mL/min/1.73m2 and indicating an underestimation of creatinine-eGFR. eGFR underestimation was confirmed by Mann-Whitney U analysis; median GFR values were significantly lower for both CKD-Epi equations as compared to corresponding iohexol-measured values (2009: 85.86; 2021: 87.29; mGFR: 96.58). Despite the overall underestimation, over 14% of donor candidates with eGFR &amp;gt;90 mL/min/1.73m2 had an mGFR value &amp;lt;90 mL/min/1.73m2. Conversely, 36% - 38% of donors with normal kidney function of &amp;gt;90 mL/min/1.73m2 as determined by iohexol-mGFR had corresponding eGFR values &amp;lt;90 mL/min/1.73m2. eGFR showed a significant but poor correlation with mGFR, with R2 values of 0.2775 and 0.2803, respectively. While the 2021 eGFR equation had better accuracy as compared to the 2009 equation (p30 of 81% versus 76%), it displayed low overall accuracy with a p10 of &amp;lt;43%. Separate analysis of Black donor candidates’ eGFR and mGFR values revealed similar trends as observed for the total cohort. While exclusion of the race factor in the 2021 CKD-Epi equation slightly improved accuracy (p30 of 77% versus 72%), the correlation with mGFR remained poor for both equations (R2: 0.1455 and 0.1377 for the 2009 and 2021 equations, respectively). The results of this study confirmed that creatinine-eGFR values, regardless of the race factor, differ significantly from iohexol-mGFR. Our data shows that even potential kidney donors with eGFR &amp;gt;90 mL/min/1.73m2 cannot be presumed to have normal kidney function, while eGFR &amp;lt;90 mL/min/1.73m2 cannot accurately exclude donor candidates. We conclude that creatinine-eGFR cannot reliably serve as a substitute for mGFR in the context of living donor kidney function evaluation.

Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). Mean age was 56years, median mGFR was 62mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions.

A-091 Assessing the Reliability of Creatinine-Estimated Glomerular Filtration Rate in Living Kidney Donor Candidates: Does it Measure up to the Measured Rate?

Abstract Background A living donor kidney transplant is the best therapy option for patients with end stage renal disease (ESRD); however, it is associated with an increased risk of ESRD development in the donor. Thorough evaluation of the donor candidate’s kidney function status is essential for the appropriate selection of candidates with minimal risk of post-donation kidney dysfunction. Methods Glomerular filtration rate (GFR) values measured by iohexol plasma clearance (mGFR) and estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) creatinine equations (eGFR), with and without the race factor (2009 and 2021 CKD-Epi equations, respectively), were compared in a cohort of 303 kidney donor candidates. GFR values were analyzed using Bland-Altman plots, linear regression, Mann–Whitney U-tests, and p10 and p30 values. Results Bland-Altman analysis revealed a lack of agreement between the 2009 and 2021 CKD-Epi eGFR and corresponding mGFR values, with both equations showing a negative bias of 10–11 mL/min/1.73 m2 and indicating an underestimation of creatinine-eGFR. eGFR underestimation was confirmed by Mann Whitney U analysis; median GFR values were significantly lower for both CKD-Epi equations as compared to corresponding iohexol-measured values (2009: 85.86; 2021: 87.29; mGFR: 96.58). Despite the overall underestimation, over 14% of donor candidates with eGFR &amp;gt;90 mL/min/1.73 m2 had an mGFR value &amp;lt;90 mL/min/1.73 m2. Conversely, 36%–38% of donors with normal kidney function of &amp;gt;90 mL/min/1.73 m2 as determined by iohexol-mGFR had corresponding eGFR values &amp;lt;90 mL/min/1.73 m2. eGFR showed a significant but poor correlation with mGFR, with R2 values of 0.2775 and 0.2803, respectively. While the 2021 eGFR equation had better accuracy as compared to the 2009 equation (p30 of 81% vs 76%), it displayed low overall accuracy with a p10 of &amp;lt;43%. Separate analysis of Black donor candidates’ eGFR and mGFR values revealed similar trends as observed for the total cohort. While exclusion of the race factor in the 2021 CKD-Epi equation slightly improved accuracy (p30 of 77% vs 72%), the correlation with mGFR remained poor for both equations (R2: 0.1455 and 0.1377 for the 2009 and 2021 equations, respectively). Conclusion The results of this study confirmed that creatinine-eGFR values, regardless of the race factor, differ significantly from iohexol-mGFR. Our data shows that even potential kidney donors with eGFR &amp;gt;90 mL/min/1.73 m2 cannot be presumed to have normal kidney function, while eGFR &amp;lt;90 mL/min/1.73 m2 cannot accurately exclude donor candidates. We conclude that creatinine-eGFR cannot reliably serve as a substitute for mGFR in the context of living donor kidney function evaluation.

Metabolic implications of amino acid metabolites in chronic kidney disease progression: a metabolomics analysis using OPLS-DA and MBRole2.0 database.

As chronic kidney disease (CKD) progresses, metabolites undergo diverse transformations. Nevertheless, the impact of these metabolic changes on the etiology, progression, and prognosis of CKD remains uncertain. Our objective is to conduct a metabolomics analysis to scrutinize metabolites and identify significant metabolic pathways implicated in CKD progression, thereby pinpointing potential therapeutic targets for CKD management. We recruited 145 patients with CKD and determined their mGFR by measuring the plasma iohexol clearance, whereupon we partitioned them into four groups based on their mGFR values. Non-targeted metabolomics analysis was conducted using UPLC-MS/MS assays. Differential metabolites were identified via one-way ANOVA, PCA, PLS-DA, and OPLS-DA analyses employing the MetaboAnalyst 5.0 platform. Ultimately, we performed differential metabolite pathway enrichment analysis, using both the MetaboAnalyst 5.0 platform and the MBRole2.0 database. According to the findings of the MBRole2.0 and MetaboAnalyst 5.0 enrichment analysis, six amino acid metabolism pathways were discovered to have significant roles in the progression of CKD, with the glycine, serine, and threonine metabolism pathway being the most prominent. The latter enriched 14 differential metabolites, of which six decreased while two increased concomitantly with renal function deterioration. The metabolic analysis unveiled that glycine, serine, and threonine metabolism plays a pivotal role in the progression of CKD. Specifically, glycine was found to increase while serine decreased with the deterioration of CKD.

Accuracy-Based Glomerular Filtration Rate Assessment by Plasma Iohexol Clearance in Kidney Transplant Donors.

An accurate measurement of the glomerular filtration rate (GFR) is essential for detecting renal insufficiency in living kidney donors. Iohexol is a "near-ideal" exogenous filtration marker for GFR measurements that has attracted increasing interest in clinical practice because it is non-toxic, non-radioactive, readily available, and easy to measure. In this study, we aimed to set up a laboratory test to conveniently assess the plasma clearance of iohexol in living kidney donors. A workflow was established in the institution's infusion clinic to administer iohexol and to collect three timed blood samples from renal transplant donors. Iohexol was thereafter measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The serum proteins were precipitated and the supernatant containing iohexol was diluted prior to the LC-MS/MS analysis. The LC-MS/MS method was developed on a Thermo Vanquish UHPLC coupled with a TSQ Endura triple quadruple mass spectrometer with a total run time of 2.5 min. The analytical performance of the method was assessed. The LC-MS/MS method demonstrated a good analytical performance. To calculate the iohexol clearance rate and the GFR, automated data integration and a result calculation were accomplished by using a custom Python script. Automated result reporting was achieved using a laboratory informatics system (LIS) vendor's direct media interface. We developed and implemented a laboratory test to assess the plasma clearance of iohexol. A workflow was established in the hospital to reliably measure the GFR in living kidney donors, with a potential to be further expanded into other areas where an accurate GFR measurement is needed.

Application of GFR estimating equations to children with normal, near-normal, or discordant GFR.

The objective was to determine the extent that eGFR formulas correspond to measured plasma iohexol clearance (iGFR) in children with normal or near normal kidney function, particularly how different eGFR formulas yield discordant results. iGFR from 2 (iGFR-2pt) and 4 (iGFR-4pt) time points along with creatinine and/or cystatin C-based eGFR were measured in children with mild CKD, stages 1-2. eGFR was calculated using 6 equations: 3 under 25 (U25) formulas from the Chronic Kidney Disease in Children (CKiD) study, the full age-combined cystatin C (cysC) and creatinine spectrum (FAS-combined), the European Kidney Function Consortium (EKFC-creatinine) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) cysC-based equation. Twenty-nine children were included, of which 22 had discordant creatinine vs. cystatin C-based eGFR by ≥ 15mL/min/1.73m2. Overall, the FAS-combined had the least bias, while the U25 most accurately identified children with an eGFR < 90 mL/min/1.73m2. When Cr-eGFR was ≥ 15 mL/min higher than CysC-eGFR, the U25 creatinine eGFR was closest to iGFR-4pt. When CysC eGFR was higher, the U25-combined was closest to iGFR-4pt. The formulas that most closely approximated the measured GFR varied depending on the pattern of discordant eGFR results. Based on the results, we recommend using the CKiD U25-combined formula to screen for children with a low GFR. Either the CKiD U25-combined or FAS-combined would be recommended for changes in eGFR longitudinally. However, because all formulas were discordant from the iGFR-4pt in over a third of participants, further refinement of pediatric eGFR formulas is needed at the normal/near-normal range. A higher resolution version of the Graphical abstract is available as Supplementary information.