Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) classically presents with hypoketotic hypoglycaemia; however, this presentation is now rare following the introduction of newborn screening. While children with MCADD may produce some ketones, severe ketoacidosis has not been previously described. Here we report two patients with MCADD presenting with severe ketoacidosis in the neonatal period prior to results of newborn screening. Patient 1 presented on Day 5 with hypoglycaemia, profound ketoacidosis and circulatory shock, and developed refractory ventricular tachycardia requiring extra-corporeal membrane oxygenation. Patient 2 presented on Day 4 with severe ketoacidosis, but only borderline hypoglycaemia. The diagnosis of MCADD was rapidly confirmed in both by analysis of acylcarnitines and urine organic acids, with subsequent genetic confirmation of ACADM mutations. We conclude that MCADD should be included in the differential diagnosis of neonatal ketoacidosis, with or without hypoglycaemia.

Objective To study the performance of two contemporary sets of estimating equations for glomerular filtration rate, published by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) and EKFC (European Kidney Function Consortium) that include one (creatinine or cystatin C only) and combined (creatinine and cystatin C) biomarkers, to assess their accuracy in a population with moderate chronic kidney disease.Design Prospective cohort study.Setting Primary, secondary, and tertiary care in six centres in England. Participants were recruited from April 2014 to January 2017.Participants 1167 adults, aged ≥18 years, with moderate chronic kidney disease (estimated glomerular filtration rate 30-59 mL/min/1.73 m2 sustained over at least three months before recruitment).Main outcome measures Accuracy of estimating equations CKD-EPIcreatinine, CKD-EPIcystatin, CKD-EPIcreatinine-cystatin, EKFCcreatinine, EKFCcystatin, and EKFCcreatinine-cystatin compared with measured glomerular filtration rate (iohexol clearance). Remodelled 2021 versions of the CKD-EPI equations were also studied. Accuracy was expressed as P30 (percentage of estimates within 30% of measured glomerular filtration rate).Results Median age was 67.5 years, 58.3% of patients were men, 86.9% were white participants, and 27.8% had diabetes. Median measured glomerular filtration rate was 47.0 mL/min/1.73 m2; 57.0% of participants had albuminuria. Test calibration critically affected measurement of cystatin C. After recalibration of cystatin C, P30 values were 90.2% (CKD-EPIcreatinine), 89.5% (CKD-EPIcystatin), 94.9% (CKD-EPIcreatinine-cystatin), 88.0% (CKD-EPI(2021)creatinine), 94.9% (CKD-EPI(2021)creatinine-cystatin), 89.4% (EKFCcreatinine), 91.0% (EKFCcystatin), and 94.9% (EKFCcreatinine-cystatin). Creatinine based equations showed varying bias depending on the glomerular filtration rate level; inclusion of cystatin C in the equations improved this effect. Differences in accuracy in age, sex, and glomerular filtration rate level subgroups varied by equation. Equations combining creatinine and cystatin performed equally across age, sex, diabetes status, albuminuria status, and body mass index categories.Conclusions The CKD-EPIcreatinine equation had acceptable accuracy in a white population in England with moderate chronic kidney disease. Combined dual biomarker equations showed higher accuracy than the CKD-EPIcreatinine equation and their equivalent creatinine only equations. Further research is needed to determine the most accurate equation to use in people of black and South Asian origin living in England.

BackgroundThe continuous evaluation of GFR among youth with T1D has traditionally been difficult during the transition to adult care given distinct pediatric & adult estimated GFR (eGFR) formulas recommended by clinical practice guidelines. We aimed to assess longitudinal trends in kidney function in type 1 diabetes from adolescence to early adulthood using updated eGFR formulae and to examine associations between eGFR and clinical as well as social factors over time in this population.MethodsClinical factors including age, sex, diabetes duration, insulin therapy, BMI and HbA1c in addition to social factors including ethnicity & material deprivation (MD) were collected alongside creatinine (Cr) and cystatin c (CysC) from Canadian participants in the AdDIT & CanSOLVE CKD-SPOR studies (2009-2023). Estimated glomerular filtration rates (eGFR) derived using updated Chronic Kidney Disease in Children under 25 (CKiD U25) Cr, CysC & combined Cr-CysC formulas were evaluated longitudinally using linear mixed effects regression, as were urine albumin-creatinine ratios (uACR).ResultsYouth with type 1 diabetes ages 10 to <25 years were evaluated (N = 137) at a median 5 timepoints (IQR: 4-6) over 9.8 ± 1.3 years. As age increased, eGFRCr increased mildly (β:+1.0 ml/min/1.73m2/year; P<0.0001), whereas eGFRCysC decreased until the age of 18 (β:-3.3 ml/min/1.73m2/year; P<0.0001) and stabilized thereafter (β: +0.1 ml/min/1.73m2/year; P = 0.433). These trends nullified one another across the age range using the combined eGFRCr-CysC, which remained stable (β:-0.1 ml/min/1.73m2/year) from ages 10–25 years (P = 0.452). Sex, BMI, insulin therapy, HbA1c and MD were associated with eGFRCr-CysC over time with a large difference of +6.5 ml/min/1.73m2 seen in high relative to low MD groups (P = 0.0025). Log-transformed uACR was negatively associated with male sex (P = 0.017) and baseline diabetes duration (P = 0.049) yet positively associated with HbA1c (P = 0.021).ConclusionsDifferent eGFR trends were observed using Cr- vs. CysC-derived estimates in youth with diabetes using updated eGFR formulae. Elevations in eGFR, alongside alterations in markers of albuminuria, were associated with increased glycemia and marginalization, providing insights into key clinical and social risk factors for kidney disease monitoring in this population. (NCT01581476).

OBJECTIVES:To provide evidence on the longitudinal accuracy of glomerular filtration rate (GFR) estimating equations that include creatinine and cystatin C to monitor patients with moderate chronic kidney disease. DESIGN:Prospective, longitudinal, cohort study. SETTING:Primary, secondary, and tertiary care across six centres in England, 1 April 2014 to 31 December 2017. PARTICIPANTS:1229 adults (≥18 years) with moderate chronic kidney disease (creatinine estimated GFR of 30-59 mL/min/1.73 m2 for at least three successive months before recruitment). MAIN OUTCOME MEASURES:Ability of estimating equations to monitor GFR over three years, with slope deviations from reference measured GFR (iohexol clearance) within ±3 mL/min/1.73 m2/year indicating agreement. Ability of GFR estimating equations to detect disease progression (ie, a reduction in measured GFR of ≥25% with a reduction in disease category). RESULTS:After three years, 875 participants had measured and estimated GFR data recorded at the start and end of the study and comprised the study cohort. Median measured GFR decreased from 48.1 mL/min/1.73 m2 at baseline to 43.6 mL/min/1.73 m2 at three years. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) estimating equations. Median change in measured GFR exceeded median change in estimated GFR for all equations. All equations achieved agreement with change in measured GFR in >72.5% of participants. Dual biomarker equations showed better agreement with change in measured GFR (CKD-EPIcreatinine-cystatin 78.6% of individuals, 95% confidence interval 75.8% to 81.3%; CKD-EPI(2021)creatinine-cystatin 78.1%, 75.2% to 80.8%; and EKFCcreatinine-cystatin 80.2%, 77.4% to 82.8%) than CKD-EPIcreatinine (73.1%, 70.1% to 76.1%) (all P<0.001). Progression of kidney disease was seen in 139 (15.9%) individuals. All GFR equations had poor sensitivity (<54.1%) but good specificity (>90.4%) for identifying progression of chronic kidney disease. CONCLUSIONS:Underestimation of the reduction in GFR by estimated GFR requires further investigation. Equations that included both creatinine and cystatin C more accurately monitored change in measured GFR than equations based on one biomarker. Increased use of combined biomarker equations in clinical practice could improve disease monitoring and potentially clinical care. STUDY REGISTRATION:ISRCTN registry ISRCTN42955626.

Abstract Adolescence represents a pivotal period for the development of early diabetes-related vascular complications, primarily driven by chronic hyperglycemia and associated metabolic disturbances. Metabolomics provides a promising tool to identify biomarkers reflecting these early changes. The present study compared metabolomic profiles between adolescents with and without type 1 diabetes and assessed the impact of glycemia and short-term treatment with statins and/or ACE inhibitors on metabolite trajectories. Metabolomic data were obtained via the Nightingale platform from 341 adolescents with type 1 diabetes from the AdDIT study and 81 age- and sex-matched peers without diabetes. Two hundred and forty-nine metabolites, with 45 prioritized due to well-established links with cardiovascular disease- including lipid subfractions, amino acids, ketone bodies, and markers of renal function and inflammation—were measured at a mean age of 14.0 ± 1.8 years and re-assessed after 3.5 years in those with diabetes. At baseline, significant differences were observed in glucose, ketone bodies, amino acids, and lipid classes. Over time, adolescents with diabetes showed increases in lipid subfractions, acetoacetate, and GlycA, with HbA1c positively associated with atherogenic lipidome components. Findings from the trial arm provided strong evidence that statins attenuated rises in LDL-cholesterol (1.90 [1.79, 2.01] vs. 2.38 [2.28, 2.49] mmol/l), and weaker evidence suggestive of a small effect of ACE inhibitors in preserving HDL-cholesterol (1.50 [1.45, 1.54] vs. 1.39 [1.34, 1.43] mmol/l). These findings suggest widespread glycemia-related metabolomic perturbations in adolescents with type 1 diabetes, partially mitigated by statins and ACE inhibitors, supporting their cardioprotective role. Clinical registration : ClinicalTrials.gov ID NCT01581476 (13/04/2012) https://clinicaltrials.gov/study/NCT01581476 .

Diabetic kidney disease (DKD) is the primary cause of kidney failure in type 1 diabetes (T1D). Early identification of subclinical DKD is based on albuminuria and glomerular filtration rate (GFR). However, no GFR equations have been validated in youth with T1D. This study evaluates the performance of GFR equations in youth with T1D. We compared a direct measure of GFR (mGFR) via plasma clearance of exogenous inulin, with estimated GFR (eGFR). eGFR was calculated with the following equations: Full-Age Spectrum (FAS-height and FAS-age); revised Lund-Malmö (LM-Rev); European Kidney Function Consortium (EKFC); Chronic Kidney Disease Epidemiology Collaboration, 2009 (CKD-EPI 2009); CKD-EPI 2021 (revised CKD-EPI 2009 without race adjustment); CKD-EPI40 (revised CKD-EPI 2021 with age-adjusted creatinine); Chronic Kidney Disease in Children (CKiD); CKiD Under 25 (sex-dependent); CKiD Under 25 (age- and sex-dependent); and Improving Renal Complications in Adolescents with Type 2 Diabetes through Research (iCARE). Bland–Altman analysis estimated performance (bias and accuracy (P10 and P30)). In total, 141 children and adolescents at a mean age of 13.5 ± 3.3 years (range 6.2–18.5) and diabetes duration 5.7 ± 1.6 years were included. Their mean serum creatinine was 45.6 ± 12.1 μmol/L (0.52 ± 0.14 mg/dL) and mGFR 142.3 ± 25.0 mL/min/1.73 m2. For the whole population, FAS-height (bias = 8.37 mL/min/1.73 m2; P30 = 85.1

Glycogen storage disease type Ib (GSD Ib, biallelic variants in SLC37A4) is a rare disorder of glycogen metabolism complicated by neutropenia/neutrophil dysfunction. Since 2019, the SGLT2-inhibitor empagliflozin has provided a mechanism-based treatment option for the symptoms caused by neutropenia/neutrophil dysfunction (e.g. mucosal lesions, inflammatory bowel disease). Because of the rarity of GSD Ib, the published evidence on safety and efficacy of empagliflozin is still limited and does not allow to develop evidence-based guidelines. Here, an international group of experts provides 14 best practice consensus treatment recommendations based on expert practice and review of the published evidence. We recommend to start empagliflozin in all GSD Ib individuals with clinical or laboratory signs related to neutropenia/neutrophil dysfunction with a dose of 0.3-0.4 mg/kg/d given as a single dose in the morning. Treatment can be started in an outpatient setting. The dose should be adapted to the weight and in case of inadequate clinical treatment response or side effects. We strongly recommend to pause empagliflozin immediately in case of threatening dehydration and before planned longer surgeries. Discontinuation of G-CSF therapy should be attempted in all individuals. If available, 1,5-AG should be monitored. Individuals who have previously not tolerated starches should be encouraged to make a new attempt to introduce starch in their diet after initiation of empagliflozin treatment. We advise to monitor certain safety and efficacy parameters and recommend continuous, alternatively frequent glucose measurements during the introduction of empagliflozin. We provide specific recommendations for special circumstances like pregnancy and liver transplantation.

During the COVID-19 pandemic, development of diagnostic tests was vital to chart the course and to reduce the impact of the infection. Continued testing and surveillance of vaccine escape will continue for years to come which presents an opportunity to integrate such testing into clinical biochemistry laboratories that form part of integrated healthcare testing. Here we describe a protocol for a targeted mass spectrometry based proteomic assay (COVIDCAP) developed to detect SARS-CoV-2 peptides from oro-nasopharyngeal swabs (ONP) and saliva. This uses novel SISCAPA antibodies bound to magnetic beads and subsequent analysis of captured and purified SARS-CoV-2 nucleocapsid (NCAP) peptides. The method involves immediate deactivation of the sample using an ethanolic solution. This simultaneously inactivates the virus and denatures viral proteins at sampling in contrast to the approach for RT-PCR testing, with benefits for the assay as well as for downstream processing. A plate-based preparation of the samples involving acetone precipitation followed by a short tryptic digestion and subsequent immunocapture allows LC-MS detection and quantification of peptides from the NCAP protein, in a 3-minute inject-to-inject assay with an LOD of 20 attomoles from starting sample. For 576 ONP swab samples taken as exemplars here, the sensitivity and specificity of this analysis is shown to be 97.0% and 96.6% respectively.

Objectives: To examine the relationship between kidney hyperfiltration during adolescence and subsequent changes in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) in a young cohort of participants with type 1 diabetes. Additionally, to explore urinary mitochondrial DNA to nuclear DNA ratio (mtDNA:nDNA) as a marker of metabolic stress and its association with early changes in kidney function. Methods: Eighty adolescents were studied at baseline (mean [SD] age 14.2 [1.5] years; mean diabetes duration 6.7 [3.0] years) and at follow-up 9.2 (1.3) years later. Blood pressure, HbA1c, lipids, eGFR, UACR, and heart rate variability were assessed at each visit. Urinary mtDNA:nDNA was measured by quantitative PCR. Results: Overall, 4.2% of participants had diabetic kidney disease at follow-up. Hyperfiltration at baseline (>135 mL/min/1.73 m2 ) was seen in 31% of adolescents and was associated with a decline in eGFR at follow-up when adjusted for sex, diabetes duration, and HbA1c (hyperfiltration -1.46 [3.07] mL/min/1.73 m2 /year vs non-hyperfiltration -0.51 [2.48] mL/min/1.73 m2 /year, P = .02). Participants with hyperfiltration also had higher odds of undergoing rapid eGFR decline (>3 mL/min/1.73 m2 /year) compared to those without hyperfiltration (odds ratio 14.11 [95% CI 2.30-86.60], P = .004). Baseline urinary mtDNA:nDNA was significantly associated with both greater annual rate of eGFR decline and rapid eGFR decline in univariable but not multivariable modeling. Conclusion: Hyperfiltration during adolescence is significantly associated with greater reduction in eGFR and higher risk of rapid eGFR decline after similar to 9 years, following transition into young adulthood in type 1 diabetes. Urinary mtDNA:nDNA measured during adolescence may be a novel predictor of early changes in kidney function

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.

Ciclosporin (CyA) and methotrexate (MTX) are frequently prescribed drugs for the treatment of atopic dermatitis in children and young people. Both can affect renal function and frequent blood monitoring is standard to monitor safety. We show that both CyA and MTX are not associated with decreased renal function and are safe and effective as a treatment for atopic dermatitis in children and young people.

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.

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease resulting in acute liver failure in early infancy, hypophosphataemic rickets, neurological crises, liver cirrhosis and risk of hepatocellular carcinoma later on in life. It is caused by the deficiency of the enzyme fumarylacetoacetate hydrolase which is involved in the terminal step of the catabolic pathway of tyrosine. Diagnosis is made through clinical suspicion supported by biochemical abnormalities that result from accumulation of upstream metabolites. Detection of succinylacetone (SA) in dried blood spot or urine remains pathognomonic, however it is not always detectable. Here we describe three cases of HT1 presenting with atypical biochemistry, where SA was not always detectable, highlighting the importance of an additional disease biomarker, 4-oxo-6-hydroxyheptanoate.

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.

Background Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline ( n = 1167) and their ability to detect change over 3 years ( n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components ( n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs ( n = 875). Setting Primary, secondary and tertiary care. Participants Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine–cystatin equation (94.9%) was superior ( p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/−17.7, with lower reference change values for estimated glomerular filtration rate. Limitations Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration This trial is registered as ISRCTN42955626. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment ; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort’s distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial’s intervention was targeted (national). Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. NCT01581476. Registered on 20 April 2012.

BACKGROUND A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to 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/1.73m², 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 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.

Early detection of CKD using point of care creatinine and eGFR testing improves patient management outcomes. We undertook a field study to evaluate the use of a whole blood creatinine/eGFR device to screen a rural Nicaraguan population to determine the variability between creatinine methods and specimen types. All specimens including capillary and venous dried blood spots (DBS) were tested with an isotope dilution liquid chromatography mass spectrometry (ID-LCMS) gold standard method. This is to our knowledge the first time a capillary whole blood (POC) method has been directly compared to the gold standard IDMS method, through the novel approach of using dried blood spots. Capillary and venous whole blood specimens were obtained and tested directly with the BCMS method, and then, DBS samples were prepared. Venous plasma specimens were tested using three laboratory analyzer creatinine methods. DBS were sent to the site performing IDLCMS. Control samples were also prepared to assess the stability of shipment and storage of DBS. The ID-LCMS method was aligned using primary and secondary standards. Sixty-six (66) patients participated in the study, and the CKD prevalence rate was 7.8%. While all creatinine methods showed a good correlation to ID-LCMS, there was a positive bias (mean absolute bias range: 0.21-0.63 mg/dL). All methods used were 100% sensitive, but specificity varied from 62.7 to 94.9% with PPV ranging from 25 to 62.5%. A correction factor was used to align the values from each method to ID-LCMS which improved the specificity of each method. This study used a unique DBS approach to align capillary whole blood creatinine to ID-LCMS. To ensure reliability of BCMS for identifying screened patients with CKD, it is important to establish IDMS traceability and alignment prior to undertaking CKD studies.

Identifying genetic determinants for longitudinal changes in albumin excretion in individuals with type 1 diabetes may help identify those that are predisposed to renal, retinal and cardiovascular complications. Most studies have focussed on genetic predisposition to diabetic kidney disease and used cross-sectional measurements of urinary albumin excretion, but with limited success. Here, we utilise the wealth of longitudinal data and bio-samples collected from cohorts of childhood-onset type 1 diabetes followed over the last 30 years to describe a novel trajectory phenotype quantifying urinary albumin excretion changes during childhood and adolescence. We conducted a genome-wide association study and fine-mapping analysis for albumin excretion in 1584 individuals, finding one signal for cross-sectional albumin excretion close to GALNTL6 (rs150766792), which validated in a previous independent study, and a novel genome-wide significant signal for albumin excretion trajectory in the CDH18 gene region (rs145715205). Our trajectory phenotype quantifies albumin progression and offers a complementary measure to an albumin excretion phenotype based on a single measurement (i.e. most recent data collection) or an average of repeated measurements in longitudinal studies. It can be used to identify genetic or other risk factors which predict better or worse prognosis, thus facilitating the development of new preventive and therapeutic approaches.