The effect of a multidisciplinary care clinic on the outcomes in pediatric chronic kidney disease.

BACKGROUND: Current best evidence-based practice for children with chronic kidney disease (CKD) attempts to achieve good clinical outcomes through careful management of comorbidities and is likely best achieved with a multidisciplinary care (MDC) CKD clinic. METHODS: In this retrospective study of children with CKD in British Columbia, Canada, we analyzed clinical outcomes in a cohort of 73 CKD patients from 2003 under a standard care model and a second cohort of 125 CKD patients from 2009 under a MDC clinic model. RESULTS: Patient demographics were similar, but there was a decrease in the percentage of patients with CKD stage 3-5 in 2009 (59 vs. 75 %; p = 0.002), although the absolute number increased. After adjustment for severity of CKD, hemoglobin was significantly higher (13.0 g/dl vs. 12.2 g/dl, p < 0.03), calcium was significantly higher (9.6 mg/dl vs. 9.1 mg/dl, p < 0.001), and albumin was significantly higher (4.4 g/dl vs. 3.8 g/dl, p < 0.001) in the 2009 MDC cohort. The rate of disease progression, assessed by annualized estimated glomerular filtration rate (eGFR) slope, improved from -4.0 ml/min/1.73 m(2) in the 2003 cohort to 0.5 ml/min/1.73 m(2) in the 2009 cohort (p < 0.01). Blood pressure control was better in 2009 although not statistically significant. CONCLUSIONS: Multidisciplinary care improved the outcomes of children with CKD especially in anemia management, bone mineral metabolism, nutrition, and renal disease progression.

Arterial stiffness and functional properties in chronic kidney disease patients on different dialysis modalities: an exploratory study.

BACKGROUND: Abnormalities of vascular function and accumulation of oxidative stress have been associated with chronic kidney disease (CKD). Dialysis modalities, peritoneal dialysis (PD) and haemodialysis (HD) may differentially impact on vascular function and oxidative stress. METHODS: Patients undergoing living donor transplantation were studied for vascular stiffness using pulse wave velocity measurements, and inferior epigastric arteries were harvested to examine in vitro stiffness and functional properties and evidence of oxidative stress. Forty-one patients were studied representing PD (n = 12), HD (n = 14) and non-dialysed recipients (n = 15). RESULTS: We demonstrated differences in stiffness from in vivo and in vitro measurements such that non-dialysis < HD < PD groups. The stiffness measurements did not correlate with duration of CKD nor dialysis duration, but did so with phosphate levels (r = 0.356, P = 0.02). From the in vitro isometric force experiments, HD arteries demonstrated decreased contractility and endothelium-dependent relaxation compared with PD and non-dialysis vessels. Level of oxidative stress (as indicated by the 8-isoprostane level) was 30% higher in HD arteries than in PD arteries. Protein expression of inducible nitric oxide synthase, NADPH subunits and xanthine oxidase was upregulated in HD arteries, while superoxide dismutase was downregulated. The compromised vascular function in HD arteries was improved by pharmacological means that eliminated oxidative stress. CONCLUSIONS: We report associations between vasomotor function and oxidative stress in the vasculature of patients receiving different dialysis therapies. Oxidative stress, which may be differentially augmented during PD and HD, may play an important role in the vascular dysfunction in dialysis populations.

Matrix metalloproteinase-2 and -9 exacerbate arterial stiffening and angiogenesis in diabetes and chronic kidney disease.

AIMS: Chronic kidney disease (CKD) and diabetes are the prominent risk factors of cardiovascular disease (CVD). Matrix metalloproteinase (MMP)-2 and -9 regulate vascular structure by degrading elastic fibre and inhibit angiogenesis by generating angiostatin. We hypothesized that MMP-2 and -9 were up-regulated in the arterial vasculature from CKD patients with diabetes, compared with those without diabetes. METHODS AND RESULTS: During living donor transplantation procedures, arteries from donors (n = 8) and recipients (non-diabetic, n = 8; diabetic, n = 8; matched in age, gender, and dialysis treatments) were harvested. Diabetic arteries had increased MMP-2 and -9 activities by 42 and 116% compared with non-diabetic ones. Diabetic arteries were the stiffest, and the stiffness measurement was highly correlated with the summation of MMP-2 + MMP-9 activities (r = 0.738, P = 0.0002). Pulse wave velocity measurements correlated with MMP activity (r = 0.683, P = 0.005). Elastic fibre degradation and calcification were worst in diabetic vessels. The phosphate level, which was 25% higher in diabetic patients, correlated with MMP activity (r = 0.513, P = 0.04) and in vitro stiffness (r = 0.545, P = 0.03), respectively. Angiostatin expression was doubled, whereas vascular endothelial growth factor was 50% reduced in diabetic compared with non-diabetic vessels. Microvascular density in diabetic vessels was 48% of that in non-diabetic ones, and it was strongly associated with MMP activity (r = -0.792, P < 0.0001) and vasorelaxation (r = 0.685, P = 0.0009). CONCLUSION: Using a matched case-control design, we report up-regulation of MMP-2 and -9 in diabetic CKD arteries and correlate those with stiffening, impaired angiogenesis, and endothelial dysfunction. These findings may help to explain the high susceptibility of CVD in diabetic and non-diabetic CKD patients.