Background: Coronary artery calcification (CAC) is common in chronic kidney disease (CKD) patients, and is demonstrable in fifty percent of incident dialysis patients. Therefore, the process of CAC initiation likely occurs in the pre-dialysis period. Pre-dialysis CKD patients have been shown to have a substantially higher burden of CAC than age and sex matched controls from the general population. Consequently, the hypothesis that CKD itself is a risk factor for CAC occurrence is biologically plausible. Objective: 1) To quantify the relationship between CKD and CAC in stage three to five CKD patients without known cardiovascular disease. 2) To estimate the strengths of associations between traditional cardiovascular disease risk factors, non- traditional cardiovascular disease risk factors and CAC in this patient population. Methods: This cross-sectional study investigated one hundred and nineteen CKD patients (excluding dialysis) receiving care at a single hospital in Kingston, Ontario, Canada. For the primary objective, correlational analyses were performed to evaluate associations between a priori selected variables of kidney function and CAC scores, as well as other a priori chosen variables of interest. Results: Mean and median CAC scores were 566.5 SD: 1108 and 111 (inter-quartile range 2 to 631.5) respectively. CAC correlated with age (r = 0.44, p<0.001), body mass index (r = 0.28, p = 0.002), high density lipoprotein cholesterol (r = -0.23, p = 0.01), diabetes mellitus (r = 0.23, p = 0.01), and the cardiovascular risk score (r = 0.35; p < 0.001). By multivariable linear regression controlling for eGFR and diabetes, age (ß = 0.05, 95% CI 0.03-0.06; p<0.001), body mass index (ß = 0.04, 0.02 - 0.07; p=0.001), and serum calcium (ß = 0.9, 0.15 - 1.6; p=0.02), were risk factors for CAC. Results from multivariable logistic regression modeling demonstrated consistent findings. Limitations: Inadequate sample size and uncontrolled confounding are possible limitations, but are unlikely to have changed the main study findings. Conclusions: In this study, traditional cardiovascular disease risk factors and serum calcium were associated with coronary artery calcification. No association was demonstrated between CKD and CAC. Studies exploring potential protective mechanisms against coronary artery calcification are needed.

No description available.

The impact of habitually consuming a high protein (HP) diet at the upper limit of the acceptable macronutrient distribution range (AMDR) on kidney health is unknown. The current study was designed to test the hypothesis that long-term consumption of a diet providing 35% of energy as protein will have negative consequences on renal health, as assessed in a pig model. Methods: Adult female, non-pregnant, commercial pigs (Genesus) were randomized to receive either NP (15% energy from protein) or HP (35% energy from protein) isocaloric diets for either 4 or 8 months. Diets contained whole protein sources with an animal: plant ratio of 2:1 in the NP diet to mimic the average Canadian diet. The increased protein in the HP diet was achieved by increasing egg and dairy protein sources. Body composition was measured by dual-energy X-ray absorptiometry. Glomerular volume and kidney fibrosis were evaluated on kidney sections by quantitative image analysis. The inflammatory marker monocyte chemoattractant protein-1 (MCP-1) and the growth factor transforming growth factor beta-1(TGFβ1) were assessed in renal tissue using commercial ELISA kits. Results: Pigs given the HP diet had lower body weights and percentage of body fat. Pigs consuming the HP diet had significantly higher glomerular filtration rates (GFR) and larger kidneys. Renal MCP-1 levels and renal fibrosis also were significantly higher in pigs given the HP diet, while proteinuria and renal TGFβ1 expression did not differ. Conclusion: These findings suggest that, despite the potential benefit of the HP diet on body composition, long-term intakes of protein at the upper limit of the AMDR may compromise renal health in healthy female pigs.

The Slit family of secreted proteins act as axonal repellents during embryogenesis. Slit2 via its receptor, Roundabout-1, also inhibits chemotaxis of multiple leukocyte subsets. Using static and microfluidic shear assays, we found that Slit2 inhibited multiple steps required to recruit circulating neutrophils. Slit2 blocked capture and firm adhesion of human neutrophils to and transmigration across inflamed primary vascular endothelial cells. To determine the response of Slit2 in renal ischemia reperfsuion injury, Slit2 was administered prior to bilateral renal pedicle clamping in mice. This led to significant decreases in both renal tubular necrosis score and neutrophil infiltration. Administration of Slit2 also prevented elevation of plasma creatinine following injury in a dose-dependent manner. Furthermore, administration of Slit2 did not increase hepatic bacterial load in mice infected with L.monocytogenes infection. Collectively, these data demonstrate Slit2 as an exciting therapeutic molecule to combat renal ischemia reperfusion injury without compromising protective host innate immune functions.

The Slit family of secreted proteins act as axonal repellents during embryogenesis. Slit2 via its receptor, Roundabout-1, also inhibits chemotaxis of multiple leukocyte subsets. Using static and microfluidic shear assays, we found that Slit2 inhibited multiple steps required to recruit circulating neutrophils. Slit2 blocked capture and firm adhesion of human neutrophils to and transmigration across inflamed primary vascular endothelial cells. To determine the response of Slit2 in renal ischemia reperfsuion injury, Slit2 was administered prior to bilateral renal pedicle clamping in mice. This led to significant decreases in both renal tubular necrosis score and neutrophil infiltration. Administration of Slit2 also prevented elevation of plasma creatinine following injury in a dose-dependent manner. Furthermore, administration of Slit2 did not increase hepatic bacterial load in mice infected with L.monocytogenes infection. Collectively, these data demonstrate Slit2 as an exciting therapeutic molecule to combat renal ischemia reperfusion injury without compromising protective host innate immune functions.

No description available.

No description available.

FGF2 is expressed in renal podocytes as they differentiate <I>in-vivo</I>, as demonstrated by specific antibody staining within developing glomeruli of chicken metanephros. Mice lacking FGF2 have been generated in the laboratory by targeted deletion and kidneys of <I>Fgf2</I> deficient mice appear to develop normally. Detailed histological analysis of adult kidneys from these mice however has revealed low frequency glomerular abnormalities. Additionally, a few obvious cases of glomerulosclerosis with severe podocyte damage were observed specifically in mutant mice. Taken together these observations indicate FGF2 plays a role in podocyte development and/or function. A novel culture system that allows the induction of podocyte cell differentiation <I>in-vivo</I> has recently been developed. The system is based on isolation of conditionally immortalised podocyte cells derived from H-2K<SUP>b</SUP>tsA58 transgenic (immorto) mice. Isolation of podocyte cells from renal glomeruli of wild-type and FGF2 deficient immorto mice was performed to address the functional relevance of FGF2 in podocyte development. Conditionally immortalised wild-type podocyte cells (wild-type MPCs) display characteristic features of podocytes <I>in-vivo</I>, however Fgf2 null MPCs show striking morphological and molecular abnormalities. Mutant podocyte cells do not undergo the epithelial-to-mesenchymal transformation (EMT) associated with normal podocyte maturation and, correspondingly, fail to differentiate. The EMT mediator <I>Slug</I> is up-regulated as wild-type cells differentiate but is missing in mutant cells, suggesting this transcription factor acts downstream of FGF signalling to mediate EMT associate maturation of podocytes. <I>Fgf7</I> and <I>Fgf10</I> expressions are lost in <I>Fgf2</I> deficient MPC cells, but not in <I>Fgf2</I> deficient kidney cortex, affording an explanation to the emergence of a stronger defect <I>in-vitro</I>.

No description available.

The impact of habitually consuming a high protein (HP) diet at the upper limit of the acceptable macronutrient distribution range (AMDR) on kidney health is unknown. The current study was designed to test the hypothesis that long-term consumption of a diet providing 35% of energy as protein will have negative consequences on renal health, as assessed in a pig model. Methods: Adult female, non-pregnant, commercial pigs (Genesus) were randomized to receive either NP (15% energy from protein) or HP (35% energy from protein) isocaloric diets for either 4 or 8 months. Diets contained whole protein sources with an animal: plant ratio of 2:1 in the NP diet to mimic the average Canadian diet. The increased protein in the HP diet was achieved by increasing egg and dairy protein sources. Body composition was measured by dual-energy X-ray absorptiometry. Glomerular volume and kidney fibrosis were evaluated on kidney sections by quantitative image analysis. The inflammatory marker monocyte chemoattractant protein-1 (MCP-1) and the growth factor transforming growth factor beta-1(TGFβ1) were assessed in renal tissue using commercial ELISA kits. Results: Pigs given the HP diet had lower body weights and percentage of body fat. Pigs consuming the HP diet had significantly higher glomerular filtration rates (GFR) and larger kidneys. Renal MCP-1 levels and renal fibrosis also were significantly higher in pigs given the HP diet, while proteinuria and renal TGFβ1 expression did not differ. Conclusion: These findings suggest that, despite the potential benefit of the HP diet on body composition, long-term intakes of protein at the upper limit of the AMDR may compromise renal health in healthy female pigs.