Impact of a screen, triage and treat program for identifying chronic disease risk in Indigenous children.

BACKGROUND: The First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis project was a point-of-care screening program in rural and remote First Nations communities in Manitoba that aimed to identify and treat hypertension, diabetes and chronic kidney disease. The program identified chronic disease in 20% of children screened. We aimed to characterize clinical screening practices before and after intervention in children aged 10-17 years old and compare outcomes with those who did not receive the intervention. METHODS: This observational, prospective cohort study started with community engagement and followed the principles of ownership, control, access and possession (OCAP). We linked participant data to administrative data at the Manitoba Centre for Health Policy to assess rates of primary care and nephrology visits, disease-modifying medication prescriptions and laboratory testing (i.e., glycosylated hemoglobin [HbA1c], estimated glomerural filtration rate [eGFR] and urine albumin- or protein-to-creatinine ratio). We analyzed the differences in proportions in the 18 months before and after the intervention. We also conducted a 1:2 propensity score matching analysis to compare outcomes of children who were screened with those who were not. RESULTS: We included 324 of 353 children from the screening program (43.8% male; median age 12.3 yr) in this study. After the intervention, laboratory testing increased by 5.8% (95% confidence interval [CI] 1.1% to 10.1%) for HbA1c, by 9.9% (95% CI 4.2% to 15.5%) for eGFR and by 6.2% (95% CI 2.3% to 10.0%) for the urine albumin- or protein-to-creatinine ratio. We observed significant improvements in laboratory testing in screened patients in the group who were part of the program, compared with matched controls. INTERPRETATION: Chronic disease surveillance and care increased significantly in children after the implementation of a point-of-care screening program in rural and remote First Nation communities. Interventions such as active surveillance programs have the potential to improve the chronic disease care being provided to First Nations children.

Association of Bone Mineral Density With Fractures Across the Spectrum of Chronic Kidney Disease: The Regina CKD-MBD Study.

BACKGROUND: Recent studies have demonstrated that measurement of areal bone mineral density by dual-energy x-ray absorptiometry (DXA) predicts fractures in patients with chronic kidney disease (CKD). However, whether fracture risk prediction through bone mineral density (BMD) is enhanced due to the assessment of biochemical markers of chronic kidney disease and mineral and bone disease (CKD-MBD) or clinical risk factors is not clear. We hypothesized that in a select cohort of patients managed in a CKD clinic, that combining T-Scores with biochemical markers would optimize fracture discrimination than using DXA alone. OBJECTIVE: To examine the relationships among BMD, biochemical markers of CKD-MBD, and fracture risk across Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate (GFR) categories G3a to G5. DESIGN: Retrospective study. SETTING: Patients were recruited from the multidisciplinary CKD clinic, Regina General Hospital, Canada. PATIENTS: A total of 374 patients who received a DXA scan upon initial referral to Regina Multidisciplinary CKD Program from January 31, 2001 to January 31, 2010, were included in this study. The patients were followed for a total of 5 years. METHODS: We conducted a retrospective review of 374 consecutive patients who underwent DXA imaging at the point of entry into our multidisciplinary CKD program. Areal BMD, T- and Z-Scores were obtained at the lumbar spine, total hip, mean of left and right femoral neck, and the one-third radius. We collected data on demographic, cross-sectional biochemical markers of mineral metabolism and fractures (identified through self-reported questionnaires, hospital electronic medical records, and physician billing records). We were able to gather data on 8/11 variables of Fracture Risk Assessment (FRAX) tool. RESULTS: In our cohort, 14.3% of GFR categories G3a and G3b, 15.7% of GFR category G4, and 19.7% of GFR category G5 experienced a clinical fracture during the study period. On multivariate analysis, each decline of 1.0 SD in total hip BMD T-Score was associated with a significant increase in the risk of fracture (OR = 1.46, 95% confidence interval [CI], 1.12-1.89). Adding CKD-MBD markers and clinical risk factors did not further contribute to the model. Low BMD was the only independent risk factor for fracture in patients with CKD. LIMITATIONS: Self-reporting by patients and administrative records were used to identify fractures. We did not perform spine imaging to ascertain morphometric vertebral fractures. We were unable to gather all 11 variables of FRAX score and information on ethnicity. We were unable to capture site of fracture (hips, spine, etc) from billing records. Albumin excretion rates were not collected at baseline. Treatment of the underlying bone disease with pharmacotherapeutic agents may have attenuated patients' fracture risk and thus underestimated the association between BMD and future fracture. CONCLUSIONS: Our findings confirm that BMD predicts fracture. The addition of cross-sectional CKD-MBD parameters and clinical risk factors to BMD did not add to fracture prediction. Prospective studies should investigate the utility of longitudinal biochemical markers on improving fracture risk assessment.

CONTEXTE: Des études récentes ont démontré qu'il était possible de prédire les fractures chez les patients atteints d'insuffisance rénale chronique (IRC) avec une mesure de la densité minérale osseuse (DMO) surfacique par absorptiométrie biénergétique à rayons X (DXA). On ignore cependant si la valeur prédictive de la DMO est améliorée par l'analyze des biomarqueurs des troubles minéraux et osseux associés à l'IRC (TMO-IRC) ou des facteurs de risque cliniques. Nous avons émis l'hypothèse que, dans une cohorte choisie de patients suivis en clinique d'IRC, la combinaison des scores T et des marqueurs biochimiques optimiserait la discrimination des fractures par rapport à l'utilization de la DXA seule. OBJECTIF: L'étude visait à établir un lien entre la DMO, les biomarqueurs des TMO-IRC et le risque de fractures chez les patients présentant un débit de filtration glomérulaire (DFG) de catégories G3a à G5 selon la classification du KDIGO (Kidney Disease Improving Global Outcomes). TYPE D'ÉTUDE: Étude rétrospective. CADRE: Les patients ont été recrutés à la clinique multidisciplinaire d'IRC de l'hôpital général de Régina (Canada). SUJETS: Ont été inclus les 374 patients ayant passé un test d'imagerie DXA entre le 31 janvier 2001 et le 31 janvier 2010 lors de leur aiguillage vers le program multidisciplinaire d'IRC de Régina. Les patients ont été suivis sur une période de cinq ans. MÉTHODOLOGIE: Nous avons mené une étude rétrospective portant sur 374 patients consécutifs examinés par DXA à leur admission au program. La DMO surfacique et les scores T et Z ont été mesurés au rachis lombaire, à la hanche totale, à la moyenne des cols fémoraux droit et gauche, et au tiers du radius. On a recueilli les caractéristiques démographiques des patients, les données sur les marqueurs biochimiques transversaux du métabolisme minéral et les fractures subies (recensées à l'aide d'un questionnaire d'auto-déclaration et par consultation des dossiers médicaux électroniques et des registres de facturation des médecins). Nous sommes parvenus à rassembler des données sur huit variables des onze de l'outil FRAX (Fracture Risk Assessment tool). RÉSULTATS: Dans notre cohorte, 14,3 % des patients avec un DFG de catégorie G3a-G3b, 15,7 % des patients avec un DFG de catégorie G4 et 19,7 % des patients avec un DFG de catégorie G5 ont subi une fracture clinique au cours de la période d'étude. Dans l'analyze multivariée, chaque déclin d'un point d'écart-type au score T de la DMO à la hanche a été associé à une augmentation significative du risque de fracture (RR = 1,46; IC 95 %: 1,12-1,89). L'ajout des marqueurs des TMO-IRC et des facteurs de risque cliniques n'a pas contribué davantage au modèle. Une faible DMO s'est avérée le seul facteur de risque indépendant de subir une fracture chez les patients atteints d'IRC. LIMITES: Les fractures ont été identifiées à partir des dossiers administratifs et par auto-déclaration des patients. Nous n'avons pas procédé à l'imagerie de la colonne vertébrale pour confirmer les fractures vertébrales morphométriques. Nous n'avons pas été en mesure de rassembler les onze variables du score FRAX ni les informations sur l'origine ethnique des patients. Les registres de facturation ne nous ont pas permis d'établir le site de la fracture (hanche, rachis ou autre). Les taux initiaux d'excrétion de l'albumine n'ont pas été mesurés. Le traitement de l'ostéopathie sous-jacente à l'aide d'agents pharmacothérapeutiques pourrait avoir atténué le risque de fracture des patients et ainsi, sous-évalué l'association entre la DMO et de futures fractures. CONCLUSION: Nos résultats confirment que la DMO est prédictive du risque de fractures. L'ajout des paramètres transversaux des TMO-IRC et des facteurs de risque cliniques à la mesure de DMO n'en a pas amélioré la valeur prédictive. Des études prospectives devraient examiner l'intérêt des marqueurs biochimiques longitudinaux pour améliorer l'évaluation du risque de fracture.

Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. RESULTS: Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (>400 mg/mo for most studies) and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (>200 mg/mo for most studies) and mortality (eight studies; n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). CONCLUSIONS: Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.

Noncanonical autophagy promotes the visual cycle.

Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components, but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.