Congenital nephron number varies five-fold among normal humans, and individuals at the lower end of this range may have an increased lifetime risk for essential hypertension or renal insufficiency; however, the mechanisms that determine nephron number are unknown. This study tested the hypothesis that common hypomorphic variants of the RET gene, which encodes a tyrosine kinase receptor critical for renal branching morphogenesis, might account for subtle renal hypoplasia in some normal newborns. A common single-nucleotide polymorphism (rs1800860 G/A) was identified within an exonic splicing enhancer in exon 7. The adenosine variant at mRNA position 1476 reduced affinity for spliceosome proteins, enhanced the likelihood of aberrant mRNA splicing, and diminished the level of functional transcript in human cells. In vivo, normal white newborns with an rs1800860(1476A) allele had kidney volumes 10% smaller and cord blood cystatin C levels 9% higher than those with the rs1800860(1476G) allele. These findings suggest that the RET(1476A) allele, in combination with other common polymorphic developmental genes, may account for subtle renal hypoplasia in a significant proportion of the white population. Whether this gene variant affects clinical outcomes requires further study.

Congenital nephron number ranges widely in the human population. Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury, but the factors that set nephron number during kidney development are unknown. In renal-coloboma syndrome, renal hypoplasia and reduced nephron number are due to heterozygous mutations of the PAX2 gene. This study tested for an association between a common haplotype of the PAX2 gene and subtle renal hypoplasia in normal newborns. A PAX2 haplotype was identified to occur in 18.5% of the newborn cohort, which was significantly associated with a 10% reduction in newborn kidney volume adjusted for body surface area. This haplotype was also associated with reduced allele-specific PAX2 mRNA level in a human renal cell carcinoma cell line. Subtle renal hypoplasia in normal newborns may be partially due to a common variant of the PAX2 gene that reduces mRNA expression during kidney development.

These illustrations will be incorporated into a child-friendly asthma action plan that enables the child to be involved in his or her asthma self-management care.

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A palliative care service provider may add or decrease overall operational costs to the healthcare system. This study assessed the costs of managing respite care for children with life-limiting illness at the Children's Hospital of Eastern Ontario for the 12-month period both before and after services at Roger's House (RH, a paediatric hospice) was made available. The opening and operation of RH for providing respite care resulted in a minimization of operational costs (n = 66 patients, mean decrease of $4,251.95 per month per patient).