The Direct Economic Burden of Gout in an Elderly Canadian Population.

Objective: To estimate the direct healthcare cost and resource use from the public payer perspective between patients with incident gout and matched gout-free patients in Ontario.

Methods: Patients with incident gout aged ≥ 66 with uninterrupted Ontario Health Insurance Plan (OHIP) coverage in the 1-year baseline period were included in the study. Patients with gout were indexed at first gout diagnosis or prescription over the study period April 1, 2008, to March 31, 2014.

Exploring the Distribution of Prescription for Sulfonylureas in Patients with Type 2 Diabetes According to Cardiovascular Risk Factors Within a Canadian Primary Care Setting.

Background: A growing body of evidence generated from observational studies and meta-analyses has begun to illustrate the potential adverse cardiovascular (CV) risk profile associated with sulfonylurea (SU) use. Specifically, the use of an SU has been demonstrated to be associated with increased mortality and a higher risk of stroke with more CV events associated with SU use having been reported in subgroups of patients with a history of CV disease, elderly and a higher body mass index.

Objective: The objective of the current study was to explore the distribution of established atherosclerotic CV disease and CV risk factors amongst patients with diabetes on an SU using a Canadian primary care dataset for the 2013 calendar year.

Canonical WNT signaling during kidney development.

The canonical WNT signaling pathway plays a crucial role in patterning of the embryo during development, but little is known about the specific developmental events which are under WNT control. To understand more about how the WNT pathway orchestrates mammalian organogenesis, we studied the canonical beta-catenin-mediated WNT signaling pathway in kidneys of mice bearing a beta-catenin-responsive TCF/betaGal reporter transgene. In metanephric kidney, intense canonical WNT signaling was evident in epithelia of the branching ureteric bud and in nephrogenic mesenchyme during its transition into renal tubules.

Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2.

During fetal kidney development, the extent of ureteric bud (UB) branching will determine final nephron endowment for life. Nephron number varies widely among normal humans and those who are born at the low end of the nephron number spectrum may be at risk for essential hypertension in adulthood. Little is known about how nephron number is set.

Suppression of ureteric bud apoptosis rescues nephron endowment and adult renal function in Pax2 mutant mice.

The molecular mechanisms that set congenital nephron number are unknown. However, humans with modest suboptimal nephron number may be at increased risk for essential hypertension, and those with more severe nephron deficits at birth may develop progressive renal insufficiency. A model of branching morphogenesis during fetal kidney development in which the extent of ureteric bud arborization is dependent on suppression of programmed cell death has been proposed.

PAX2 activates WNT4 expression during mammalian kidney development.

The transcription factor PAX2 is expressed during normal kidney development and is thought to influence outgrowth and branching of the ureteric bud. Mice with homozygous null Pax2 mutations have developmental defects of the midbrain-hindbrain region, optic nerve, and ear and are anephric. During nephrogenesis, PAX2 is also expressed by mesenchymal cells as they cluster and reorganize to form proximal elements of each nephron, but the function of PAX2 in these cells is unknown.

Renal hypoplasia: lessons from Pax2.

The functions of Pax2 during renal development are many. It organizes caudal descent of the nephric duct, emergence of the ureteric bud, branching morphogenesis, and sustained arborization of the collecting system. In this review, we use lessons from the study of Pax2 as organizing principles to focus on the developmental processes which, if disrupted, might lead to renal hypoplasia in humans.

Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk.

In renal-coloboma syndrome (RCS), null mutations of the PAX2 gene cause renal hypoplasia due to a congenital deficit of nephrons; affected individuals may develop renal insufficiency in childhood. During normal kidney development, PAX2, is expressed at high levels throughout the arborizing ureteric bud (UB); recent observations suggest that one of its key roles is to suppress apoptosis in this collecting duct lineage. The authors hypothesized that increased UB cell apoptosis due to PAX2 haploinsufficiency must directly influence the rate of branching morphogenesis in developing kidney and the number of nephrons that can be formed before birth, when nephrogenesis in humans comes to an end.

Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice mimics the renal-coloboma syndrome.

In humans, PAX2 haploinsufficiency causes renal-coloboma syndrome (RCS) involving eye abnormalities, renal hypoplasia, and renal failure in early life. The authors previously showed that heterozygous mutant Pax2 mice have smaller kidneys with fewer nephrons, associated with elevated apoptosis in the ureteric bud (UB). However, PAX2 may have a variety of developmental functions such as effects on cell fate and differentiation.