Reference values for serum creatinine in children younger than 1 year of age

Reliable reference values of enzymatically assayed serum creatinine categorized in small age intervals are lacking in young children. The aim of this study was to determine reference values for serum creatinine during the first year of life and study the influence of gender, weight and height on these values. Serum creatinine determinations between 2003 and 2008 were retrieved from the hospital database. Strict exclusion criteria ensured the selection of patients without kidney damage. Correlation analysis was performed to evaluate the relation between height, weight and serum creatinine; the Mann–Whitney test was used to evaluate the relation between gender and serum creatinine. A broken stick model was designed to predict normal serum creatinine values. Mean serum creatinine values were found to decrease rapidly from 55 μmol/L on day 1 to 22 μmol/L in the second month of life; they then stabilized at 20 μmol/L until the seventh month, followed by a slight increase. No significant relation was found between serum creatinine and gender, weight and height. We present here reference values of serum creatinine in infants not at risk of decreased renal function. The absence of a relationship with gender, weight and height confirms that height-based equations to estimate glomerular filtration rate are less useful in patients of this age group

Cystatin C: current position and future prospects.

Abstract Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. This review summarises current knowledge about the physiology of cystatin C and about its use as a renal marker, either alone or in equations developed to estimate the glomerular filtration rate. This paper also reviews recent data about the other applications of cystatin C, particularly in cardiology, oncology and clinical pharmacology. Clin Chem Lab Med 2008;46:1664-86

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 nea

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Common genetic variants contribute to risk of transposition of the great arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Multiwavelength variability and correlation studies of Mrk 421 during historically low X-ray and γ-ray activity in 2015-2016

We report a characterization of the multiband flux variability and correlations of the nearby (z = 0.031) blazar Markarian 421 (Mrk 421) using data from Metsahovi, Swift, Fermi-LAT, MAGIC, FACT, and other collaborations and instruments from 2014 November till 2016 June. Mrk 421 did not show any prominent flaring activity, but exhibited periods of historically low activity above 1 TeV (F->1 TeV 0.1 TeV) gamma-rays, which, despite the low activity, show a significant positive correlation with no time lag. The HRkeV and HRTeV show the harder-when-brighter trend observed in many blazars, but the trend flattens at the highest fluxes, which suggests a change in the processes dominating the blazar variability. Enlarging our data set with data from years 2007 to 2014, we measured a positive correlation between the optical and the GeV emission over a range of about 60 d centred at time lag zero, and a positive correlation between the optical/GeV and the radio emission over a range of about 60 d centred at a time lag of 43(-6)(+9) d. This observation is consistent with the radio-bright zone being located about 0.2 parsec downstream from the optical/GeV emission regions of the jet. The flux distributions are better described with a lognormal function in most of the energy bands probed, indicating that the variability in Mrk 421 is likely produced by a multiplicative process