Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study

Background: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure.Methods: This longitudinal observational study will recruit kidney transplant recipients aged 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation.Discussion: The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population.Transplantation and autoimmunit

Adenine Phosphoribosyltransferase Deficiency : a potentially reversible cause of CKD

Adenine phosphoribosyltransferase (APRT) enzyme deficiency is an important and potentially reversible cause of progressive chronic kidney disease. It is a rare, autosomal recessive disorder that was first described in 19741 with more than 40 known mutations2, 3 and estimated prevalence of 1 in 50,000 to 100,000 persons.2, 4, 5 The APRT enzyme is important for the conversion of adenine to adenosine monophosphate in the salvage purine pathway. Deficiency of this enzyme results in the metabolism of adenine into 2,8-dihydroxyadenine (DHA) by xanthine oxidase (xanthine dehydrogenase) (Figure 1a). DHA is highly insoluble in urine and will precipitate to cause either urolithiasis or crystal nephropathy. There are no known extrarenal manifestations and reasons for this remains unclear given the extensive tissue distribution of this enzyme

A novel cause of chronic viral meningoencephalitis: Cache Valley virus.

ObjectiveImmunodeficient patients are particularly vulnerable to neuroinvasive infections that can be challenging to diagnose. Metagenomic next generation sequencing can identify unusual or novel microbes and is therefore well suited for investigating the etiology of chronic meningoencephalitis in immunodeficient patients.MethodsWe present the case of a 34-year-old man with X-linked agammaglobulinemia from Australia suffering from 3 years of meningoencephalitis that defied an etiologic diagnosis despite extensive conventional testing, including a brain biopsy. Metagenomic next generation sequencing of his cerebrospinal fluid and brain biopsy tissue was performed to identify a causative pathogen.ResultsSequences aligning to multiple Cache Valley virus genes were identified via metagenomic next generation sequencing. Reverse transcription polymerase chain reaction and immunohistochemistry subsequently confirmed the presence of Cache Valley virus in the brain biopsy tissue.InterpretationCache Valley virus, a mosquito-borne orthobunyavirus, has only been identified in 3 immunocompetent North American patients with acute neuroinvasive disease. The reported severity ranges from a self-limiting meningitis to a rapidly fatal meningoencephalitis with multiorgan failure. The virus has never been known to cause a chronic systemic or neurologic infection in humans. Cache Valley virus has also never previously been detected on the Australian continent. Our research subject traveled to North and South Carolina and Michigan in the weeks prior to the onset of his illness. This report demonstrates that metagenomic next generation sequencing allows for unbiased pathogen identification, the early detection of emerging viruses as they spread to new locales, and the discovery of novel disease phenotypes. Ann Neurol 2017;82:105-114

Dwell time and risk of central-line-associated bloodstream infection in neonates

© 2017 The Healthcare Infection Society Background Umbilical venous catheters (UVCs) or peripherally inserted central catheters (PICCs), widely used in high-risk neonates, may have a threshold dwell time for subsequent increased risk of central-line-associated bloodstream infection (CLABSI). Aim To evaluate the CLABSI risks in neonates having either UVC, PICC, or those having both sequentially. Methods The study included 3985 infants who had UVC or PICC inserted between 2007 and 2009 cared for in 10 regional neonatal intensive care units: 1392 having UVC only (group 1), 1317 PICC only (group 2), and 1276 both UVC and PICC (group 3). Findings There were 403 CLABSIs among 6000 venous catheters inserted, totalling 43,302 catheter-days. CLABSI rates were higher in group 3 infants who were of lowest gestation (16.9 per 1000 UVC-days and 12.5 per 1000 PICC-days; median: 28 weeks) when compared with group 1 (3.3 per 1000 UVC-days; 37 weeks) and group 2 (4.8 per 1000 PICC-days; 30 weeks). Life table and Kaplan–Meier hazard analysis showed that UVC CLABSI rate increased stepwise to 42 per 1000 UVC-days by day 10, with the highest rate in group 3 (85 per 1000 UVC-days). PICC CLABSI rates remained relatively stable at 12–20 per 1000 PICC-days. Compared to PICC, UVC had a higher adjusted CLABSI risk controlled for dwell time. Among group 3, replacing UVC electively before day 4 may have a trend of lower CLABSI risk than late replacement. Conclusion There was no cut-off duration beyond which PICC should be removed electively. Early UVC removal and replacement by PICC before day 4 might be considered