Reliability of different estimated glomerular filtration rate as measures of renal function in children with sickle cell disease.

BACKGROUND: There is no reliable marker for detecting early renal disease in early children with sickle cell disease (SCD). Estimation of glomerular filtration rate (eGFR) as derived from the height/plasma creatinine formula is dependent on the accuracy of the creatinine analytical method used. The aim of this study was to evaluate different equations for eGFR. METHODS: Children aged 5-16 years recruited. mGFR was obtained using plasma disappearance of Inutest/Iohexol, serum creatinine (SCr) was measured either by standard laboratory method or by tandem mass spectrometry (MSMS). Estimated GFR was then calculated either by "Bedside Schwartz method" or by the full-age spectrum (FAS) equation. FINDINGS: A total of 79 patients (mean age 9.8 ± 4.0 years). A revised eGFR constant was calculated for Schwartz equation from the slope of the plot of height/plasma creatinine versus mGFR. Mean values for mGFR (132.7 ± 32.1 ml/min/1.73m2) and eGFR methods compared: eGFR from standard SCr was significantly higher (144.2 ± 37.3 ml/min/1.73m2, p = 0.008). The MSMS eGFR showed the lowest SD (SD = 27.5), while both FAS eGFR and FAS-height eGFR showed the highest correlation coefficient (r = 0.67). INTERPRETATION: eGFR calculation based on height and SCr determined with MSMS traceable creatinine is more reliable than Schwartz formula using jaffe/enzymatic methods in SCD children.

Clinical utilization of dried blood spot nitisinone (NTBC) and succinylacetone (SA) concentrations in hereditary tyrosinaemia type 1 - A UK centre experience.

BACKGROUND: Dried blood spot monitoring of nitisinone and succinylacetone in hereditary tyrosinaemia type 1 patients is not widely available in the United Kingdom. Currently, biochemical monitoring utilizes urinary succinylacetone, blood spot tyrosine and phenylalanine monitoring, which can lack in convenience and accuracy, respectively. METHODS: We report the development of a dried blood spot assay for nitisinone and succinylacetone and analysed retrospective clinical and biochemical data for hereditary tyrosinaemia type 1 patients from a single UK centre. RESULTS: A total of 13 hereditary tyrosinaemia type 1 patients were evaluated. Eleven presented with liver dysfunction (two with associated renal tubulopathy) and two were detected by early sibling screening. All patients (age 0.03-22 months) were commenced on a tyrosine-/phenylalanine-restricted diet and nitisinone at diagnosis. Ten patients were on twice daily dosing and three were on single daily dosing at the start of monitoring. One patient from each dosing group swapped between dosing regimens at 20 years of age and 8 months of age, respectively. A total of 684 dried blood spot samples were analysed; 80% of nitisinone concentrations were between 9.2 and 27 µmol/L when succinylacetone was <0.3 µmol/L. Patients on twice daily dosing regimens had significantly higher nitisinone concentration compared with those on once daily dosing (P < 0.0001). The median dose required in the twice daily doing group was significantly lower when compared with once daily dosing. CONCLUSIONS: Dried blood spot monitoring for nitisinone and succinylacetone concentrations in hereditary tyrosinaemia type 1 patients is a rapid and convenient method which allows physicians to individualize treatment plans and observe adherence to treatment.

Urinary biomarkers in pelvic-ureteric junction obstruction: a systematic review.

Antenatal hydronephrosis is a common finding detected on prenatal ultrasound. Although hydronephrosis will spontaneously resolve in the majority of newborns, there is a significant amount of cases that will worsen with the risk of a progressive and permanent loss of renal function. There is an increasing concern among experts that the current criteria for evaluation of clinically significant obstructions are limited. Our aim is to provide a systematic review of the available literature on biomarkers of renal injury, potential targets for diagnosis and prognosis of children with hydronephrosis. The main search was conducted in the electronic databases from inception through March 2019 using various combinations of the keywords: pelvic-ureteric [All Fields] AND junction [All Fields] AND obstruction [All Fields] AND "biomarkers" [MeSH Terms] OR "biomarkers" [All Fields] OR "biomarker" [All Fields]. To broaden the research, additional articles were identified through hand-searching review of the references reported in each study previously selected. Histopathological studies, studies with no control group or with participants suffering from concomitant urological diseases and articles published in language other than English were excluded. Data on study design, sample size, average patient age, hydronephrosis definition used, surgical indication, duration and pattern of follow-up, details on biomarker studied, diagnostic test characteristics, area under the curve (AUC) on receiver operating characteristic (ROC) analysis with the best cut-off (BCO) values, sensitivity, specificity and outcomes were all collected. 38 articles analysing 41 biomarkers were selected. The most frequent proteins investigated were neutrophil gelatinase-associated lipocalin (NGAL) (n=9; 23.7%), monocyte chemotactic peptide-1 (MCP1) (n=8; 21.1%), transforming growth factor ß1 (TGFß1) (n=7; 18.4%), epidermal growth factor (EGF) (n=6; 15.8%) and kidney injury molecule 1 (KIM 1) (n=6; 15.8%). Twenty-seven (71.1%) studies evaluated the effect of pyeloplasty on voided urine biomarker concentrations, comparing their values before and after surgery. Twelve (31.6%) studies investigated the correlation between preoperative biomarker concentration and the anterior posterior renal pelvis diameter (DAP) while 20 (52.6%) studies investigated the correlation between preoperative biomarker concentration with the split renal function (SRF) measured on nuclear medicine assessments. ROC curves were used to investigate the performance of urinary biomarkers in the total patient data set in 27 (71.1%) studies. Some biomarkers offer promising results. However, a critic analysis of the published studies demonstrates bias and lack of consistency suggesting that larger multicentre and carefully designed prospective studies are still needed to evaluate the clinical usefulness of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive hydronephrosis.

Measurement of urine indolylacroylglycine is not useful in the diagnosis or dietary management of autism.

To measure urine indolylacroylglycine (IAG) excretion using the IAG:creatinine ratio in children with autism spectrum disorder (ASD) compared with two groups of age matched controls, one with special needs but without ASD (SEN) and one typically developing (TD) and in subgroups with/without current gastrointestinal problems and ASD with and without regression. IAG:creatinine ratio was measured in the urine of 279 children aged 10-14 years: 129 children with ASD (28 with and 101 without regression), 62 SEN controls and 88 TD controls. The prevalence of gastro-intestinal symptoms (GIS) was recorded. No differences were found in the urine IAG:creatinine ratio among groups ASD, TD and SEN; nor in the ASD groups with/without regression, nor in those with/without GIS. This study finds no evidence of increased urine IAG excretion in children with ASD, with or without GIS or with or without regression. Urinary IAG measurements in children with ASD offer no support for increased presence of neuroactive peptides proposed to result from increased gut permeability. We found measurement of urinary IAG to have no value in the diagnosis of autism or in the dietary management of children with ASD. Autism Res 2017, 10: 408-413. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.