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ABSTRACT Background Creatinine-based equations are the most used to estimate glomerular filtration rate (eGFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the re-expressed Lund-Malmö Revised (r-LMR) and the European Kidney Function Consortium (EKFC) equations are the most validated. The EKFC and r-LMR equations have been suggested to have better performances in young adults, but this is debated. Methods We collected data (GFR) measured by clearance of an exogenous marker (reference method), serum creatinine, age and sex from 2366 young adults (aged between 18 and 25 years) both from Europe and the USA. Results In the European cohorts (n = 1892), the bias (in mL/min/1.73 m²) was systematically better for the EKFC and r-LMR equations compared with the CKD-EPI equation [2.28, 95% confidence interval (1.59; 2.91), –2.50 (–3.85; –1.76), 17.41 (16.49; 18.47), respectively]. The percentage of estimated GFR within 30% of measured GFR (P30) was also better for EKFC and r-LMR equations compared with the CKD-EPI equation [84.4% (82.8; 86.0), 87.2% (85.7; 88.7) and 65.4% (63.3; 67.6), respectively]. In the US cohorts (n = 474), the bias for the EKFC and r-LMR equations was better than for the CKD-EPI equation in the non-Black population [0.97 (–1.69; 3.06), –2.62 (–5.14; –1.43) and 7.74 (5.97; 9.63), respectively], whereas the bias was similar in Black US individuals. P30 results were not different between the three equations in US cohorts. Analyses in sub-populations confirmed these results, except in individuals with high GFR levels (GFR ≥120 mL/min/1.73 m²) for whom the CKD-EPI equation might have a lower bias. Conclusions We demonstrated that both the EKFC and r-LMR creatinine-based equations have a better performance than the CKD-EPI equation in a young population. The only exception might be in patients with hyperfiltration.

Abstract Objective To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. Design Development and validation study Setting 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). Participants 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. Main outcome measure The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. Results The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient’s creatinine level, age, and sex ( https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/ ). Conclusion A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. Trial registration ClinicalTrials.gov NCT05229939 .

Abstract Background: Altered hemodynamics in liver disease often results in overestimation of glomerular filtration rate (GFR) by creatinine-based GFR estimating (eGFR) equations. Recently, we have validated a novel eGFR equation based on serum myo-inositol, valine, and creatinine quantified by nuclear magnetic resonance spectroscopy in combination with cystatin C, age and sex (GFRNMR). We hypothesized that GFRNMRcould improve chronic kidney disease (CKD) classification in the setting of liver disease. Results: We conducted a retrospective multicenter study in 205 patients with chronic liver disease (CLD), comparing the performance of GFRNMRto that of validated CKD-EPI eGFR equations, including eGFRcr (based on creatinine) and eGFRcr-cys (based on both creatinine and cystatin C), using measured GFR as reference standard. GFRNMR outperformed all other equations with a low overall median bias (-1 vs. -6 to 4 ml/min/1.73 m2 for the other equations; p < 0.05) and the lowest difference in bias between reduced and preserved liver function (-3 vs. -16 to -8 ml/min/1.73 m2for other equations). Concordant classification by CKD stage was highest for GFRNMR (59% vs. 48% to 53%) and less biased in estimating CKD severity compared to the other equations. GFRNMR P30 accuracy (83%) was higher than that of eGFRcr (75%; p = 0.019) and comparable to that of eGFRcr-cys (86%; p = 0.578). Conclusions: Addition of myo-inositol and valine to creatinine and cystatin C in GFRNMR further improved GFR estimation in CLD patients and accurately stratified liver disease patients into CKD stages.

ABSTRACT Background Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). Methods White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. Results For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P &gt; .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P &lt; .0001), males 1.42 ± 0.31 (P &lt; .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts. Conclusion Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.

Assessment of renal function relies on the estimation of the glomerular filtration rate (eGFR). Existing eGFR equations, usually based on serum levels of creatinine and/or cystatin C, are not uniformly accurate across patient populations. In the present study, we expanded a recent proof-of-concept approach to optimize an eGFR equation targeting the adult population with and without chronic kidney disease (CKD), based on a nuclear magnetic resonance spectroscopy (NMR) derived ‘metabolite constellation’ (GFRNMR). A total of 1855 serum samples were partitioned into development, internal validation and external validation datasets. The new GFRNMR equation used serum myo-inositol, valine, creatinine and cystatin C plus age and sex. GFRNMR had a lower bias to tracer measured GFR (mGFR) than existing eGFR equations, with a median bias (95% confidence interval [CI]) of 0.0 (−1.0; 1.0) mL/min/1.73 m2 for GFRNMR vs. −6.0 (−7.0; −5.0) mL/min/1.73 m2 for the Chronic Kidney Disease Epidemiology Collaboration equation that combines creatinine and cystatin C (CKD-EPI2012) (p < 0.0001). Accuracy (95% CI) within 15% of mGFR (1-P15) was 38.8% (34.3; 42.5) for GFRNMR vs. 47.3% (43.2; 51.5) for CKD-EPI2012 (p < 0.010). Thus, GFRNMR holds promise as an alternative way to assess eGFR with superior accuracy in adult patients with and without CKD.

AimThe Cockcroft‐Gault (CG) creatinine‐based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over‐ or underdosing.MethodsIn a cross‐sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification‐of‐Diet‐in‐Renal‐Diseases (MDRD), Chronic‐Kidney‐Disease‐Epidemiology (CKD‐EPI), Lund‐Malmö‐Revised (LMR) and European‐Kidney‐Function‐Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.ResultsThe CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD‐EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5‐25 kg/m2, all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30‐accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG.ConclusionsThe CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine‐based equations.

Abstract Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels &lt;120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%. Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.