APOL1-Associated glomerular disease among African-American children: A collaboration of the chronic kidney disease in children (CKiD) and nephrotic syndrome study network (NEPTUNE) cohorts

Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 (APOL1) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: The Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE). Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)].Within studies, HR children had lower initial estimated glomerular filtration rate (EGFR) (CKiD: 53 versus 69 mL/min/1.73 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). Longitudinal EGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus-3% per year). Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1-Associated glomerular disease. Further study is needed to determine the generalizability of these findings

Genetic drivers of kidney defects in the digeorge syndrome

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P = 4.5×1014). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-Altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver

Retinal vascular caliber changes after intravitreal triamcinolone treatment for diabetic macular edema

10.1167/iovs.08-1678Investigative Ophthalmology and Visual Science49114707-4711IOVS

Estimation of air quality degradation due to Saharan dust at Nouakchott, Mauritania, from horizontal visibility data

It is now irrefutable that air pollution caused by large amounts of Total Suspended Particulates (TSP) and respiratory particulates or Particulate Matter less than 10 mu m in aerodynamic diameter (PM10) has numerous undesired consequences on human health. Air quality degradation far from the African continent, in the US and in Europe, caused by high concentrations of African dust, is seen as a major threat even though most of these countries are very distant from the Sahara. Surprisingly, no estimates of TSP or PM10 levels near the Saharan dust source are available. Based on horizontal visibility observations which are reduced by the presence of dust in the atmosphere, TSP and PM10 levels are estimated throughout the year 2000 at Nouakchott-Airport, Mauritania, using relations found in the literature. It appears that concentrations of particles are significant both in terms magnitude and frequency, as the 24-hour PM10 thresholds established by the US EPA National Ambient Air Quality Standards and the EU Limits Values for Air Quality were exceeded 86 and 137 times, respectively. The average annual concentration is far above air quality standards and estimated at 159 mu g m(-3) for TSP and 108 mu g m(-3) for PM10. These very high particulate levels are likely to represent an important public health hazard and should be considered as a major environmental risk

Contested voices? Methodological tensions in creative visual research with children

This paper contributes to the body of work within the social studies of childhood on creative visual methods and the emerging critique on the participatory assumptions of child-centred creative visual methodology. Drawing on ethnographically informed research with a group of children aged 8-12 which utilised a range of creative methods including child-led video and photography, the paper provides a methodological focus on the children’s interactions with the adult research team, each other and with the children whom they filmed, interviewed and photographed. The paper suggests that attention to the dynamics between children as researchers and participants is essential for understanding how children’s voices are made (and diminished) in child-led creative visual methods. Methodological attention to the ways in which children’s voices are differently (and unequally) heard in the research encounter is essential for evaluating what such methods bring to research with children and challenges theorizations of a singular children’s voice suggested in the literature