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BackgroundCurrent equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.MethodsWe developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.ResultsIn the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.ConclusionsNew eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

AbstractA low eGFRcystatin C/eGFRcreatinine-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 Skåne 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 eGFRcystatin C/eGFRcreatinine-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 eGFRcystatin C/eGFRcreatinine-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 eGFRcystatin C/eGFRcreatinine-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 eGFRcystatin C/eGFRcreatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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, β2-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. [ABSTRACT FROM AUTHOR]

Estimation or measurement of glomerular filtration rate (GFR) is generally required for optimal treatment of patients. Plasma creatinine has been used for estimation of GFR since 1926 and plasma cystatin C since 1979. The creatinine level is strongly dependent upon muscle mass and as the average muscle mass of different populations may vary, creatinine-based GFR-estimating equations have since 1999 used more than 10 different race coefficients to improve the diagnostic performance of such equations. But 'race' cannot be determined by biological measurements and is thus an ill-defined biological entity and controversial as it involves self-reporting and social considerations. In contrast, cystatin C-levels are virtually independent of muscular mass and cystatin C-based GFR-estimating equations do not require race coefficients for reliable estimation of GFR. The use of cystatin C-based GFR-estimating equations, alone or in conjunction with creatinine-based GFR-estimating equations, is therefore highly recommended to eliminate the use of race coefficients in estimating GFR. Although sex is a more biology-oriented parameter than race, sex terms may in some cases be controversial, involving self-reporting and social considerations. However, sex terms are not required for adequate estimation of GFR using cystatin C-based equations. [ABSTRACT FROM AUTHOR]

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 eGFR cystatin C to eGFR creatinine 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 eGFR cystatin C and eGFR creatinine 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 eGFR difference and the eGFR ratio 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 eGFR difference is not superior to the eGFR ratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

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., (© 2024. The Author(s).)

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 Skåne 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.

Background and Hypothesis: The estimation of glomerular filtration rate (GFR) is one main 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. 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 51Cr-EDTA). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ± 30% of mGFR)., Results: In the whole population (n = 6 158), median [IQR] age was 61 [47;72] years, with 45.8% women. Mean mGFR was 60 [39;82] mL/min/1.73m². Compared to non-diabetic individuals (n = 5 124), diabetic patients (n = 1 034) were older, more frequently male, heavier, and had lower mGFR. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic 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 equation combining creatinine and cystatin C present a better performance. If accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more due to differences in GFR levels than to the diabetic status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts., Methods: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed., Results: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males., Conclusion: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Aim: The 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., Methods: In 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., Results: The 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/m 2 , all equations performed similarly, and for BMI < 18.5 kg/m 2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m 2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m 2 ). The four more recent equations also classified mGFR stages better than CG., Conclusions: The 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., (© 2021 British Pharmacological Society.)

Glomerular filtration rate (GFR) is estimated by creatinine or cystatin C-based GFR-estimating equations. Those based upon creatinine, but not those based upon cystatin C, use "race" terms due to that different populations differ in average muscular mass, influencing the creatinine, but not the cystatin C, level. "Race" is not a biological, but a sociological term, determined by self-assesment. New international studies therefore strongly recommend use of cystatin C-based GFR-estimating equations.