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The use of an ACE inhibitor and a statin did not change the albumin-to-creatinine ratio over time. (Funded by the Juvenile Diabetes Research Foundation and others; AdDIT ClinicalTrials.gov number, NCT01581476 .).

Purpose of reviewThis article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive.IssueChronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow. Compounding these complexities are the variations in outcomes for patients with CKD and difficulties predicting who is most likely to develop complications over time. Clearly these gaps in our knowledge and understanding of CKD need to be filled, but the current state of CKD research is not where it needs to be. A culture of clinical trials and inquiry into the disease is lacking, and much of the existing evidence base addresses the concerns of the researchers but not necessarily those of the patients.Program overviewThe Canadian Institutes of Health Research (CIHR) has launched the national Strategy for Patient-Oriented Research (SPOR), a coalition of federal, provincial, and territorial partners dedicated to integrating research into care. Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is one of five pan-Canadian chronic kidney disease networks supported through the SPOR. The vision of Can-SOLVE CKD is that by 2020 every Canadian with or at high risk for CKD will receive the best recommended care, experience optimal outcomes, and have the opportunity to participate in studies with novel therapies, regardless of age, sex, gender, location, or ethnicity.Program objectiveThe overarching objective of Can-SOLVE CKD is to accelerate the translation of knowledge about CKD into clinical research and practice. By focusing on the patient’s voice and implementing relevant findings in real time, Can-SOLVE CKD will transform the care that CKD patients receive, and will improve kidney health for future generations.

Aims/hypothesis High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus. Methods Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFR INULIN ], n=28) or normofiltration (n=21) and healthy control individuals (n=18).Results Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA 1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165±9 vs 113±2 and 116±4 ml min, respectively, p< 0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p<0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophagederived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colonystimulating factor (p≤0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p<0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p<0.01). Conclusions/interpretation Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.

BackgroundChildren with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters.Methods and results199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0–12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e’ (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a’ (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e’ (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (−20.4 ± 2.3 vs. −19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (−19.0 ± 1.9 vs. −19.8 ± 1.5 % p < 0.001) in T1D.ConclusionsAdolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.

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OBJECTIVE Baseline data from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) indicated that tertiles of urinary albumin-to-creatinine ratios (ACRs) in the normal range at age 10–16 years are associated with risk markers for diabetic nephropathy (DN) and cardiovascular disease (CVD). We aimed to determine whether the top ACR tertile remained associated with DN and CVD risk over the 2–4-year AdDIT study. RESEARCH DESIGN AND METHODS One hundred fifty adolescents (mean age 14.1 years [SD 1.6]) with baseline ACR in the upper tertile (high-ACR group) recruited to the AdDIT trial, who remained untreated, and 396 (age 14.3 years [1.6]) with ACR in the middle and lower tertiles (low-ACR group), who completed the parallel AdDIT observational study, were evaluated prospectively with assessments of ACR and renal and CVD markers, combined with carotid intima-media thickness (cIMT) at baseline and end of study. RESULTS After a median follow-up of 3.9 years, the cumulative incidence of microalbuminuria was 16.3% in the high-ACR versus 5.5% in the low-ACR group (log-rank P &lt; 0.001). Cox models showed independent contributions of the high-ACR group (hazard ratio 4.29 [95% CI 2.08–8.85]) and HbA1c (1.37 [1.10–1.72]) to microalbuminuria risk. cIMT change from baseline was significantly greater in the high- versus low-ACR group (mean difference 0.010 mm [0.079], P = 0.006). Changes in estimated glomerular filtration rate, systolic blood pressure, and hs-CRP were also significantly greater in the high-ACR group (P &lt; 0.05). CONCLUSIONS ACR at the higher end of the normal range at the age of 10–16 years is associated with an increased risk of progression to microalbuminuria and future CVD risk, independently of HbA1c.

Background and Objective Celiac disease (CD), the most common genetically‐based food intolerance, affects 3% to 16% of children with type 1 diabetes (T1D). Treatment involves lifelong adherence to a gluten‐free diet (GFD). Individualized dietary education is resource‐intensive. We, therefore, sought to develop and test the usability of an e‐learning module aimed at educating patients and caregivers regarding implementation of the GFD in children with concurrent CD and T1D. Methods An interactive e‐learning module was developed based on extensive review of CD, T1D, and educational literature. A mixed‐methods usability testing approach was used to refine and evaluate the module, using qualitative semi‐structured interviews, observations, and satisfaction and knowledge questionnaires in two iterative cycles. The module was refined based on themes identified from each usability cycle. Results Eighteen patients (8 in cycle 1, 10 in cycle 2) and 15 caregivers (7 in cycle 1, 8 in cycle 2) participated. Patient participants had CD and T1D for a mean (SD) of 6.1 ± 5.1 and 8.3 ± 5.5 years, respectively. Their mean age was 13.5 ± 4.5 years. Thematic analysis of usability interviews showed the module to be appealing and resulted in minor module revisions after each cycle to improve usability. Mean satisfaction scores post‐module completion were high (4.67 ± 0.54), indicating participants were “very satisfied” with the education. Knowledge test scores increased significantly from pre‐ to post‐module completion (P = 0.001). Conclusion A multifaceted user‐centered usability approach demonstrated that an innovative, interactive e‐learning module is effective in knowledge retention and can provide comprehensive and accessible information in the implementation of the GFD teaching in children with CD and T1D.