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International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: A new cystatin C based European Kidney Function Consortium (EKFC CysC ) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFC Crea ). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor Q CysC ., Methods: Rescaling factor Q CysC 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 Q CysC -age relationship based on 4 th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFC CysC 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., Results: The EKFC CysC with the simple Q CysC -value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m 2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFC CysC with the more complex 4 th degree Q CysC -value. The arithmetic mean of the EKFC Crea and EKFC CysC with the simple Q CysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m 2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4 th degree Q CysC -polynomial., Conclusion: Using exactly the same Q CysC of 0.83 mg/L, the adult EKFC CysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFC Crea and EKFC CysC results in bias closer to zero and P30 slightly over 90%., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown., Methods: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex., Results: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone., Conclusions: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.)., (Copyright © 2023 Massachusetts Medical Society.)

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.)

Purpose of Review: There is currently a heated debate ongoing whether or not to use the race coefficient for black people in the Modification of Diet in Renal Diseases and Chronic Kidney Disease Epidemiology-equation. The use of the race coefficient is thought by several American authors as a source of discrimination., Recent Findings: It has recently been shown that the race coefficient is inaccurate in European and African black people. Therefore, it seems that the race correction is more a correction for black Americans, rather than for black in general. This 'correction' at the glomerular filtration rate (GFR)-level has been criticized, as it is misleading, and should be abandoned, as it has not been shown that GFR is different between black and white people. However, as differences in creatinine generation between black and white people might exist, a correction or adjustment, different for black and white people, at the creatinine level might be required, very similar to the different scaling of creatinine for males and females., Summary: The current debate on the race coefficient is particularly difficult because of the absence of good scientific data in black subjects and there lies the real discrimination in our opinion. We therefore call for future dedicated studies, both in Europe and USA., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Inadequate vitamin D status is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate vitamin D status in European women aged over 80 years. Assessments of serum 25-hydroxyvitamin D levels (25(OH)D) were performed on 8532 European women with osteoporosis or osteopenia of which 1984 were aged over 80 years. European countries included in the study were: France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed: <75 nmol/L (30 ng/ml) and <50 nmol/L (20 ng/ml). Mean (SD) age of the patients was 83.4 (2.9) years, body mass index was 25.0 (4.0) kg/m(2) and level of 25(OH)D was 53.3 (26.7) nmol/L (21.4 [10.7] ng/ml). There was a highly significant difference of 25(OH)D level across European countries (p<0.0001). In these women aged over 80 years, the prevalence of 25(OH)D inadequacy was 80.9% and 44.5% when considering cut-offs of 75 and 50 nmol/L, respectively. In the 397 (20.0%) patients taking supplemental vitamin D with or without supplemental calcium, the mean serum 25(OH)D level was significantly higher than in the other patients (65.2 (29.2) nmol/L vs. 50.3 (25.2) nmol/L; P<0.001). This study indicates a high prevalence of vitamin D (25(OH)D) inadequacy in old European women. The prevalence could be even higher in some particular countries., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)