Selenium (Se), an essential trace element, is linked to poor prognosis in heart failure (HF) and kidney disease. Se deficiency (serum Se < 70 μg/L) has been associated with increased cardiovascular mortality. Selenoprotein P (SELENOP), the main Se transporter, reflects bioavailable Se. Selective glomerular hypofiltration syndrome (SGHS), defined by a cystatin C-based eGFR < 0.7 of creatinine-based eGFR, signals early kidney dysfunction and worsens HF outcomes. The prognostic role of SELENOP for SGHS and kidney-related hospitalization in HF remains unclear. PURPOSE:To assess whether SELENOP is associated with SGHS at baseline and future kidney disease hospitalization in acute HF patients. METHODS:In 570 patients hospitalized for acute HF, creatinine and cystatin C were analyzed; SELENOP was measured in the first 320 using an immunoassay. Kidney hospitalizations (ICD-10 N17-N19) were identified from regional registries. Logistic and Cox regression models evaluated SELENOP's association with SGHS and hospitalization risk, adjusting for age, sex, blood pressure, BMI, eGFR and NT-proBNP. RESULTS:Among 320 patients (mean age 75 years, 69% male), 58% had Se deficiency, and 30% had SGHS. During a median 43-month follow-up, 28 patients were hospitalized for kidney disease. Higher SELENOP was linked to lower odds of SGHS (OR 0.69; p = 0.002) and reduced risk of hospitalization for AKI or CKD (HR 0.60; p = 0.010), particularly AKI (HR 0.42; p = 0.002). SELENOP-deficiency (<3.23 mg/L) predicted AKI hospitalization (HR 4.02; p = 0.035). CONCLUSIONS:Low SELENOP is associated with SGHS and increased risk of kidney disease hospitalization, especially AKI, suggesting Se status may influence HF and renal outcomes.

[This corrects the article DOI: 10.1016/j.ekir.2025.01.030.].

BACKGROUND:In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures. METHODS:Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated. RESULTS:Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria. CONCLUSION:The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.

PURPOSE:Assess if cystatin C-derived measures of kidney function are associated with mortality in septic- and non-septic intensive care unit (ICU) patients. METHODS:Data from adult patients staying >24 h in four ICUs in Sweden from November 2015-December 2018 included. Outcomes were mortality and need for renal replacement therapy (RRT) due to acute kidney injury. Associations between cystatin C-estimated glomerular filtration rate (eGFRcys) and shrunken pore syndrome (SPS) and outcomes were assessed with Cox-regression in unadjusted and analyses adjusted for sex, age, illness severity, chronic kidney disease and creatinine. SPS was defined as a ratio between eGFRcys and eGFRcreatinine <0.6. RESULTS:In total, 4455 patients were included in the analysis, of which 32 % had sepsis. SPS was present in 7.4 % of the cohort, and 90-day mortality was 30.8 %. In sepsis- and non-sepsis patients, SPS and eGFRcys were associated with 90-day-, 1-year mortality and RRT in unadjusted analyses. In an adjusted analysis, SPS was associated with 1-year mortality in sepsis patients (hazard ratio [HR] 1.4, 95 % CI 1.1-1.9, p = 0.021), and eGFRcys was associated with RRT in both sepsis and non-sepsis patients (HR 3.1, 95 % CI 1.6-6.0, p < 0.001, eGFRcys <20 vs ≥60 ml/min/1.73m2). No other associations between eGFRcys, SPS and mortality were detected in adjusted analyses. CONCLUSION:Our finding that SPS is more robustly associated with mortality in sepsis patients than in non-sepsis patients suggests that the association between SPS and mortality may depend on underlying pathophysiology. A cystatin C-based estimate of GFR is independently associated with RRT in sepsis and non-sepsis.

Selective glomerular hypofiltration syndrome (SGHS), formerly shrunken pore syndrome, an emerging marker of glomerular dysfunction, is associated with worsened prognosis in cardiovascular disease, but its role in kidney failure remains underexplored. Osteopontin (OPN) is associated with worsening kidney function and prognosis in chronic kidney disease. To explore if increased levels of OPN and SGHS are associated with hospitalization for kidney failure in patients with acute heart failure (HF). OPN was analyzed in 315 hospitalized HF patients using a proximity extension assay. SGHS was defined as cystatin C-based estimated GFR (eGFR) < 60

The emergence of drug-resistant Gram-positive pathogens, particularlyStaphylococcus aureusandStreptococcus pyogenes, has driven the need for novel antimicrobial agents. This study explores 21 newly synthesized peptidomimetic analogues of cystatin C N-terminal fragment, designed to enhance bioactivity, solubility, and safety. These compounds were evaluated for antimicrobial potency, cytotoxicity, pro-proliferative effects, and pharmacokinetic properties. Key findings indicate that analogues A-192 and A-164 exhibited the strongest antimicrobial effects against S. aureus and S. pyogenes. Most compounds were inactive against Gram-negative bacteria. Cytotoxicity profiling identified several derivatives with low to moderate toxicity and favorable pro-proliferative effects at specific concentrations. Stability tests confirmed the robustness in aqueous and plasma environments. Computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) modeling revealed low gastrointestinal absorption, but favorable parameters for topical applications. Exploratory analyses (principal component analysis (PCA) and two-way hierarchical cluster analysis (2D-HCA)) linked structural featuressuch as branching, molecular weight, and solubility, with biological activity. These results support the potential of structurally optimized peptidomimetics as targeted, topical therapeutics for Gram-positive infections and provide a rationale for further preclinical development.

BackgroundCreatinine-based estimated glomerular filtration rate (eGFR) equations are widely used in clinical practice but exhibit inherent limitations. On the other side, measuring GFR is time consuming and not available in routine clinical practice. We developed and validated machine learning models to assess the trustworthiness (i.e. the ability of equations to estimate measured GFR (mGFR) within 10%, 20% or 30%) of the European Kidney Function Consortium (EKFC) equation at the individual level.MethodsThis observational study used data from European and US cohorts, comprising 22,343 participants of all ages with available mGFR results. Four machine learning and two traditional logistic regression models were trained on a cohort of 9,202 participants to predict the likelihood of the EKFC creatinine-derived eGFR falling within 30% (p30), 20% (p20) or 10% (p10) of the mGFR value. The algorithms were internally and then externally validated on cohorts of respectively 3,034 and 10,107 participants. The predictors included in the models were creatinine, age, sex, height, weight, and EKFC.ResultsThe random forest model was the most robust model. In the external validation cohort, the model achieved an area under the curve of 0.675 (95%CI 0.660;0.690) and an accuracy of 0.716 (95%CI 0.707;0.725) for the P30 criterion. Sensitivity was 0.756 (95%CI 0.747;0.765) and specificity was 0.485 (95%CI 0.460; 0.511) at the 80% probability level that EKFC falls within 30% of mGFR. At the population level, the PPV of this machine learning model was 89.5%, higher than the EKFC P30 of 85.2%. A free web-application was developed to allow the physician to assess the trustworthiness of EKFC at the individual level.ConclusionsA strategy using machine learning model marginally improves the trustworthiness of GFR estimation at the population level. An additional value of this approach lies in its ability to provide assessments at the individual level.

Background: A newly discovered renal syndrome, shrunken pore syndrome (SPS), has been shown to increase mortality regardless of renal function. SPS is defined as an estimated glomerular filtration rate (eGFR) of cystatin C ≤ 60% than eGFRcreatinine. We set out to study SPS in relation to the survival of heart transplantation patients with a follow-up of up to 12 years. Methods. This was a single-center cohort study including 253 consecutive patients undergoing heart transplantation. The prevalence of SPS at different time points post-transplantation and its effect on survival was evaluated using Kaplan-Meier's analysis and multivariable Cox proportional hazards regression. Results. The prevalence of SPS was 7.5% the day after transplantation (D1), which rose to 71% week 4 after surgery. There was no difference in survival for patients with SPS D1 compared to patients without SPS D1. Patients with SPS 4 weeks compared to patients without SPS 4 weeks after transplantation showed a 5- and 10-year survival of 73% vs. 93% (p = .02) and 63% vs. 90% (p = .005), respectively. SPS developed during the postoperative period was also found to be an independent predictor of mortality (HR 4.65; 95% CI 1.36-15.8). Discussion. SPS that developed in the postoperative course after heart transplantation was found to be an independent predictor of mortality with a severe negative impact on 5- and 10-year survival.

Cystatin C was identified as a marker of glomerular filtration rate (GFR) in 1979, and the parallel analysis of cystatin C and creatinine led to the identification of shrunken pore syndrome (SPS) - a new kidney disorder - in 2015. Since then, it has been shown that cystatin C in many aspects is superior to creatinine as a marker of GFR and cardiovascular risk. SPS, an entity within the selective glomerular hypofiltration syndromes (SGHS), has been demonstrated to be associated with a strong increase in morbidity and mortality in several populations. Despite the seriousness of SPS and SGHS, and the availability of potential treatments, many patients with these conditions remain undiagnosed, due to the limitations of the international Kidney Disease Improving Global Outcomes Organization (KDIGO) guidelines. Given the significant clinical advantages of cystatin C in diagnosing and treating kidney disorders, there is a need to expand the KDIGO guidelines to include cystatin C measurements alongside creatinine at least in the initial patient evaluation but also in follow-up evaluations. This would improve the early detection and management of patients with kidney diseases, ultimately enhancing patient outcomes. The present discourse summarizes the development of this understanding from the original observations in 1979 and 2015 to the latest findings.

Introduction: Discordant results between cystatin C and creatinine in estimating glomerular filtration rate (GFR) are an important medical issue. However, the equation that should be used when GFR estimates are discordant remains unclear. Methods: This cross-sectional analysis included 15,485 participants with GFR measured by the clearance of an exogenous marker, serum creatinine, and cystatin C. We studied the proportion of discordant results defined as an absolute (> 15 ml/min per 1.73 m(2)) or relative (> 20%) difference between creatinine-based estimated GFR (eGFR, eGFR(crea)) and cystatin C-based eGFR (eGFR(cys)) using different equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], and reexpressed Lund-Malm & ouml; [r-LMR]). We also researched for the best estimating equations to be used in subjects with concordant or discordant results to estimate measured GFR (mGFR). Results: In the total cohort, the proportion of subjects with discordant results (absolute or relative) was larger for CKD-EPI (35.1 and 40.6%) than for EKFC (21.9 and 31.7%) or r-LMR (22.8 and 32.8%) equations. Among discrepant results, the proportion of eGFR(cys) < eGFR(crea) was significantly higher than the proportion of eGFR(crea) < eGFR(cys) for the CKD-EPI equations, whereas the occurrence of discrepancy was similar in the 2 discrepant groups for EKFC or r-LMR. For the EKFC and r-LMR equations, but not for the CKD-EPI, the equation combining creatinine and cystatin C was consistently the closest to the mGFR in the discrepant groups. Conclusion: Based on the lower discrepancy proportion, better balance between eGFR(crea) and eGFR(cys), and better concordance with mGFR, the EKFC, and r-LMR equations should be preferred over the CKD-EPI to estimate GFR.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, beta 2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 +/- 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 +/- 5.3% and troponin-T (36 kDa) was 11.3 +/- 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 +/- 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

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.

A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. The EKFCCysC with the simple QCysC-value of 0.83 had a bias of –7.6 [95

Background The estimation of glomerular filtration rate (GFR) is one tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C has been proposed as a biomarker. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status.Methods Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR; iohexol or chromium 51-ethylenediaminetetraacetic acid). The performance of the equations was assessed by calculating bias, precision [interquartile range (IQR)] and P30 (percentage of eGFR values within +/- 30% of mGFR).Results In the whole population (N = 6158), the median age was 61 years (IQR 47-72) and 45.8% were women. The mean mGFR was 60 ml/min/1.73 m2 (IQR 39-82). Compared with non-diabetic individuals (n = 5124), diabetic patients (n = 1034) were older, more frequently male, heavier and had lower mGFR. The performance of the EKFCcys equation was similar to that of the EKFCcrea equation, but the EKFCcrea+cys equation had a better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic patients, but according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status.Conclusion We showed that the equation combining creatinine and cystatin C performed better. If the accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more likely due to differences in GFR levels rather than diabetic status. Graphical Abstract

Abstract Background and Aims Diabetes is the first cause of chronic kidney disease (CKD) worldwide. The estimation of glomerular filtration rate (GFR) is one main tool to detect CKD. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equations is the most validated in Europe. More recently, another renal biomarker, cystatin C, has been proposed. In the current analysis, we studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. Method Four cohorts from the EKFC dataset were considered in which the diabetic status was available: Lund, Sweden (n = 2,780), Berlin, Germany (n = 654), Créteil, France (n = 466), and Paris, France (n = 2,258). Serum creatinine and cystatin C were measured with calibrated assays. GFR was measured by plasma clearances (mGFR) (iohexol in Lund, Berlin and Créteil and 51Cr-EDTA in Paris). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ±30% of mGFR). As the characteristics of diabetic patients were different, we matched diabetic and non-diabetic patients using the following matching criteria: age (±3 years), sex (equal), mGFR (±3 mL/min/1.73 m²), and BMI (±2.5 kg/m²). Results In the whole population (n = 6,158), median [IQR] age was 61 [47; 72] years, with 45.8% of women. Mean measured GFR (mGFR) was 60 [39; 82] mL/min/1.73 m². Compared to non-diabetic subjects (n = 5,124), diabetic patients (n = 1,034) were older, more frequently males, heavier, had lower mGFR (45 vs 64 mL/min/1.73 m²), and higher creatinine (1.44 vs 1.06 mg/dL; p < 0.0001) and cystatin C (1.67 vs 1.20 mg/L) concentrations. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than single-biomarker equations. Globally, P30 were substantially lower in diabetic patients than in non-diabetic patients (Table). We could match data for 289 females and 546 males. The results in the matched cohorts were quite similar between diabetics and non-diabetics subjects, and this is true for every equation. Conclusion In conclusion, in a large dataset of patients including diabetics and non-diabetics, we showed that the EKFC equations are accurate in diabetic and non-diabetic patients. Combining the creatinine and cystatin C-based equations presents an added value. If accuracy of all equations seems better in non-diabetic than in diabetic subjects, it is probably more due to differences in age and (still more) in GFR levels than to the diabetic status.

A low eGFR(cystatin C)/eGFR(creatinine)-ratio is characteristic of a group of serious kidney disorders called 'Selective Glomerular Hypofiltration Syndromes'. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Sk & aring;ne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFR(cystatin C)/eGFR(creatinine)-ratio <= 0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFR(cystatin C)/eGFR(creatinine)-ratio <= 0.60 was found in a subgroup of 32 women diagnosed with 'preeclampsia with severe features'. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFR(cystatin C)/eGFR(creatinine)-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFR(cystatin C)/eGFR(creatinine)-ratio decreases to, or below, 0.60 might help avoid maternal complications.

The aim of the present study was to extend the creatinine-based Lund-Malm & ouml; GFR equation for use with rescaled cystatin C (r-LMRCys) and validate it against measured GFR (mGFR) in the EKFC cystatin C cohort of children (n = 2,293) and adults (n = 7,727). Rescaling was obtained by dividing each biomarker by a Q-value, representing the population-specific median biomarker level among healthy individuals. Validation included median bias/precision/accuracy (percent estimates within +/- 30% of mGFR, P30). Performance was compared with the EKFC-equation (EKFCCys), the CAPA cystatin C equation, the corresponding equations based on rescaled creatinine (r-LMRCr and EKFCCr) and the arithmetic mean of r-LMRCr and CAPA (r-LMRCr+CAPA), r-LMRCr and r-LMRCys (r-LMRMean), and EKFCCr and EKFCCys (EKFCMean). The overall P30 of r-LMRCys in adults was 86.2% (95% CI 85.4%-86.9%), which was 6.6 percentage points (pp; 95% CI 5.8-7.4 pp) higher than for CAPA and similar to r-LMRCr (P30 87.4%, 95% CI 86.6%-88.1%). r-LMRCys and EKFCCys exhibited similar performance both overall and across subgroups of age, sex, GFR and BMI and in children. All three arithmetic mean equations had similar P30-accuracy and generally performed better than the corresponding single-marker equations. Our results show that the Lund-Malm & ouml; GFR equation can be adapted for use with rescaled cystatin C with performance that is similar to the best-performing equations based on rescaled creatinine. The generality of the applied biomarker rescaling principle implies that the future demand for population- and biomarker-specific GFR estimating equations can be expected to decrease substantially.

In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC.

SIGNIFICANCE STATEMENT:New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. BACKGROUND:New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. METHODS:We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. RESULTS:Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias <±5 ml/min per 1.73 m 2 and P 30 >90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. CONCLUSION:CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.