In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.

Introduction: There is an increasing demand for accurately measured glomerular filtration rate (GFR). Iohexol serum clearance has become a new gold standard, but it is challenging when GFR is low and 24hour sampling is required for accurate results. The primary aim of this study was to develop an iohexol pharmacokinetic population model for accurate determination of individual GFR using limited sampling for up to 5 hours also when renal function is <40 ml/min. Methods: A nonparametric iohexol population pharmacokinetic model was developed with rich data from 176 patients. In a validation cohort of 43 patients, a model-determined GFR (iohexol clearance) using different limited sampling strategies for up to 5 hours was compared with the strategy currently used in routine care, a log-linear 2-point method. In all, 1526 iohexol concentrations were used, from patients ranging in age from 1 to 82 years and GFR from 14 to 149 ml/min. Results: The clinical 2-point method showed insufficient agreement compared with reference values; 15% of GFR values had an error of greater than AE10% even when sampling for 24 hours when estimating GFR <40 ml/min per 1.73 m 2 (standard procedure). Restricted sampling the first 5 hours with the population model required 4 samples to determine GFR accurately. This strategy showed excellent agreement with the reference; <3% of GFR values had an error greater than AE10 %. Conclusion: Using an iohexol population pharmacokinetic model allows for accurate determination of GFR within 5 hours when applying 4 optimally timed samples, even in patients with GFR <40 ml/min.

ClinicalTrials.gov , Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

BackgroundIn children, estimated glomerular filtration rate (eGFR) methods are hampered by inaccuracy, hence there is an obvious need for safe, simplified, and accurate measured GFR (mGFR) methods. The aim of this study was to evaluate different formulas and determine the optimal sampling points for calculating mGFR based on iohexol clearance measurements on blood samples drawn at two time points (GFR2p).MethodsThe GFR of 96 children with different stages of chronic kidney disease (CKD) (median age 9.2 years, range 3 months to 17.5 years) was determined using the iohexol plasma clearance, with blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 65.9 (range 6.3–153) mL/min/1.73 m2. The performance of seven different formulas with early and late normalization to body surface area (BSA) was validated against the reference.ResultsThe highest percentage (95.8 %) of GFR2p within 10 % of the reference was calculated using the formula of Jødal and Brøchner–Mortensen (JBM) from 2009, with sampling at 2 and 5 h. Normalization to BSA before correction of the distribution phase improved the performance of the original Brøchner–Mortensen method from 1972; P10 of 92.7 % compared to P10 of 82.3 % with late normalization, and a similar result was obtained with other formulas.ConclusionsGFR2p performed well across a wide spectrum of GFR levels with the JBM formula. Several other formulas tested performed well provided that early BSA normalization was performed. Blood sampling at 2 and 5 h is recommended for an optimal GFR2p assessment.

BackgroundAssessment of glomerular filtration rate (GFR) is important in kidney transplantation. The aim was to develop a kidney transplant specific equation for estimating GFR and evaluate against published equations commonly used for GFR estimation in these patients.MethodsAdult kidney recipients (n = 594) were included, and blood samples were collected 10 weeks posttransplant. GFR was measured by 51Cr-ethylenediaminetetraacetic acid clearance. Patients were randomized into a reference group (n = 297) to generate a new equation and a test group (n = 297) for comparing it with 7 alternative equations.ResultsTwo thirds of the test group were males. The median (2.5-97.5 percentile) age was 52 (23-75) years, cystatin C, 1.63 (1.00-3.04) mg/L; creatinine, 117 (63-220) μmol/L; and measured GFR, 51 (29-78) mL/min per 1.73 m2. We also performed external evaluation in 133 recipients without the use of trimethoprim, using iohexol clearance for measured GFR. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-equations. The new equation, estimated GFR (eGFR) = 991.15 × (1.120sex/([age0.097] × [cystatin C0.306] × [creatinine0.527]); where sex is denoted: 0, female; 1, male, demonstrating a better accuracy with a low bias as well as good precision compared with reference equations. Trimethoprim did not influence the performance of the new equation.ConclusionsThe new equation demonstrated superior accuracy, precision, and low bias. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-based equations.