Integrating Risk-Based Care for Patients With Chronic Kidney Disease in the Community: Study Protocol for a Cluster Randomized Trial.

BACKGROUND: A risk-based model of care for managing patients with chronic kidney disease (CKD) using the Kidney Failure Risk Equation (KFRE) has been successfully integrated into nephrology care pathways in several jurisdictions. However, as most patients with CKD can be managed in primary care, the next pertinent steps would be to integrate the KFRE into primary care pathways. OBJECTIVE: Using a risk-based approach for guiding CKD care in the primary care setting, the objective of the study is to develop, implement, and evaluate tools that can be used by patients and providers. DESIGN: This study is a multicenter cluster randomized control trial. SETTING: Thirty-two primary care clinics belonging to the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) across Manitoba and Alberta. PATIENTS: All patients at least 18 years old or older with CKD categories G3-G5 attending the participating clinics; we estimate each clinic will have an average of 185 patients with CKD. METHODS: Thirty-two primary care clinics will be randomized to receive either an active knowledge translation intervention or no intervention. The intervention involves the addition of the KFRE and decision aids to clinics' Data Presentation Tool (DPT), as well as patient-facing visual aids, a medical detailing visit, and sentinel feedback reports. Control clinics will only be exposed to current guidelines for CKD management, without active dissemination. MEASUREMENTS: Data from the CPCSSN repository will be used to assess whether a risk-based care approach affected management of CKD. Primary outcomes are as follows: the proportion of patients with measured urine albumin-to-creatinine ratio, and the proportion of patients being appropriately treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blockers. Secondary outcomes are as follows: the optimal management of diabetes (hemoglobin A1C <8.5%, and the use of sodium-glucose cotransporter-2 inhibitors in CKD G3 patients), hypertension (office blood pressure <130/80 for patients with diabetes, 140/90 for those without), and cardiovascular risk (statin prescription); prescriptions of nonsteroidal anti-inflammatory drugs; and decline in estimated glomerular filtration rate (eGFR). In addition, in a substudy, we will measure CKD-specific health literacy and trust in physician care via surveys administered in the clinic post-visit. At the provider level, we will measure satisfaction with the risk prediction tools. Lastly, at the health system level, outcomes include cost of CKD care, and appropriate referrals for patients at high risk of kidney failure based on provincial guidelines. Primary and secondary outcomes will be measured at the patient level and enumerated at the clinic level 1 year after the intervention implementation, except for decline in eGFR, which will be measured 2 years postintervention. LIMITATIONS: Limitations include scalability of the proposal in other health care systems. CONCLUSIONS: If successful, this intervention has the potential to improve the management of patients with CKD within Canadian primary care settings, leading to health and economic benefits, and influencing practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03365063.

CONTEXTE: Un modèle de soins intégrant la prévision du risque d'évolution vers l'insuffisance rénale par la KFRE (Kidney Failure Risk Equation) a été incorporé avec succès aux protocoles de soins des patients atteints d'insuffisance rénale chronique (IRC) de plusieurs provinces. Comme la plupart des patients souffrant d'IRC peuvent être pris en charge en première ligne, l'étape suivante serait d'intégrer la KFRE aux protocoles de soins de première ligne. OBJECTIFS: Avec une approche intégrant la prévision des risques dans les soins en IRC, l'étude vise à élaborer, mettre en œuvre et évaluer les outils qui pourraient être utilisés par les patients et les fournisseurs de soins en contexte de soins de première ligne. TYPE D'ÉTUDE: Il s'agit d'un essai multicentrique, contrôlé et à répartition aléatoire en grappes. CADRE: L'étude se tiendra dans trente-deux cliniques de soins de première ligne du Manitoba et de l'Alberta faisant partie du Réseau canadien de surveillance sentinelle en soins primaires (RCSSSP). SUJETS: Tous les patients adultes atteints d'IRC de stades G3-G5 fréquentant les cliniques participantes. Nous estimons que chaque clinique fournira une moyenne de 185 patients à l'étude. MÉTHODOLOGIE: Les trente-deux cliniques seront réparties aléatoirement pour recevoir ou non une intervention active de transmission des connaissances. L'intervention comprendra l'ajout de la KFRE et d'outils d'aide à la décision à l'outil actuel de présentation des données de la clinique; de même que du support visuel pour les patients, une consultation médicale détaillée et des rapports de rétroaction sentinelle. Les cliniques contrôles, quant à elles, ne seront exposées qu'aux lignes directrices actuelles pour la prise en charge de l'IRC, sans diffusion active. MESURES: Les données du registre du RCSSSP seront employées pour évaluer l'impact de l'approche intégrant la prévision du risque sur la gestion de l'IRC. Les critères de jugement principaux seront la proportion de patients pour lesquels on aura une mesure du rapport albumine/créatinine urinaire (RAC) et la proportion de patients traités adéquatement avec un inhibiteur de l'enzyme de conversion de l'angiotensine ou d'antagonistes des récepteurs de l'angiotensine. Les critères de jugement secondaires incluront la gestion optimale du diabète (hémoglobine A1C < 8,5 %, et l'emploi d'inhibiteurs de SGLT2 chez les patients de stade G3), de l'hypertension (pression sanguine en cabinet à < 130/80 pour les diabétiques et à < 140/90 pour les non-diabétiques) et du risque de maladies cardiovasculaires (prescription de statines); ainsi que la prescription d'anti-inflammatoires non stéroïdiens et un déclin du débit de filtration glomérulaire estimé (DFGe). Parallèlement, dans une étude secondaire, nous examinerons les connaissances des patients sur l'IRC et leur confiance envers les soins médicaux par le biais de sondages menés à la clinique après la consultation. Nous mesurerons également la satisfaction des fournisseurs de soins à l'égard des outils de prévention du risque. Enfin, du point de vue du système de santé, nous examinerons les coûts associés aux soins en IRC et l'aiguillage adéquat des patients dont le risque d'évolution vers l'insuffisance rénale est jugé élevé selon les lignes directrices provinciales. Les critères de jugement primaires et secondaires seront mesurés du point de vue des patients et recensés à l'échelle de la clinique un an après la mise en œuvre de l'intervention, à l'exception du déclin du DFGe qui sera mesuré deux ans après l'intervention. LIMITES: Les limites de l'étude incluent notamment l'extensibilité de la proposition à d'autres systèmes de santé. CONCLUSIONS: Si elle réussit, cette intervention pourrait améliorer la prise en charge des patients atteints d'IRC dans les établissements canadiens de première ligne, et ainsi entraîner des retombées positives en matière de santé et d'économie en plus d'influencer les lignes directrices de pratique.

Improving the Prediction of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is a potentially fatal complication of cardiac surgery. The inability to predict cardiac surgery-associated AKI is a major barrier to prevention and early treatment. Current clinical risk models for the prediction of cardiac surgery-associated AKI are insufficient, particularly in patients with preexisting kidney dysfunction. METHODS: To identify intraoperative variables that might improve the performance of a validated clinical risk score (Cleveland Clinic Score, CCS) for the prediction of cardiac surgery-associated AKI, we conducted a prospective cohort study in 289 consecutive elective cardiac surgery patients at a tertiary care center. We compared the area under the receiver operator characteristic curve (AUC) of a base model including only the CCS with models containing additional selected intraoperative variables including mean arterial pressure, hematocrit, duration of procedure, blood transfusions, and fluid balance. AKI was defined by the Kidney Disease Improving Global Outcomes 2012 criteria. RESULTS: The CCS alone gave an AUC of 0.72 (95% confidence interval, 0.62-0.82) for postoperative AKI. Nadir intraoperative hematocrit was the only variable that improved AUC for postoperative AKI when added to the CCS (AUC = 0.78; 95% confidence interval, 0.70-0.87; P = 0.002). In the subcohort of patients without preexisting chronic kidney disease (n = 214), where the CCS underperformed (AUC, 0.60 [0.43-0.76]), the improvement with the addition of nadir hematocrit was more marked (AUC, 0.74 [0.62-0.86]). Other variables did not improve discrimination. DISCUSSION: Nadir intraoperative hematocrit is useful in improving discrimination of clinical risk scores for AKI, and may provide a target for intervention.

Congenital absence of nitric oxide synthase 3 potentiates cardiac dysfunction and reduces survival in doxorubicin- and trastuzumab-mediated cardiomyopathy.

BACKGROUND: Doxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects. Among the potential mechanisms for this drug-induced cardiomyopathy, increased production of oxidative stress (OS) through a nitric oxide synthase 3 (NOS3)-dependent pathway has gained recent attention. The objective of the study was to determine the role of NOS3 and OS in a clinically relevant female murine model of DOX- and TRZ-induced heart failure. METHODS: A total of 120 female mice (60 wild-type [WT] and 60 NOS3 knockout [NOS3(-/-)]) were treated with either 0.9% saline, DOX, TRZ, or DOX with TRZ (DOX+TRZ). Serial echocardiography was performed for a total of 10 days, after which the mice were euthanized for histological and biochemical analyses. RESULTS: In WT female mice receiving DOX+TRZ, left ventricular ejection fraction (LVEF) decreased from 75 ± 3% at baseline to 46 ± 2% at day 10 (P < 0.05). In the NOS3(-/-) group, LVEF decreased from 72 ± 3% at baseline to 35 ± 2% at day 10 (P < 0.05). LVEF was significantly lower in NOS3(-/-) female mice receiving DOX+TRZ than WT mice at day 10 (P < 0.05). Compared with WT, NOS3(-/-) female mice also demonstrated increased mortality after treatment with DOX+TRZ, corroborating the echocardiographic findings. Histological analysis demonstrated increased myofibrillar degradation and loss of cell integrity in NOS3(-/-) female mice treated with DOX+TRZ. There was increased generation of oxidized phosphatidylcholine, a marker of OS, in NOS3(-/-) female mice receiving DOX+TRZ compared with control mice. CONCLUSIONS: Congenital absence of NOS3 potentiates the cardiotoxic side effects of DOX+TRZ in an acute female murine model of chemotherapy-induced cardiomyopathy.

Multimodality imaging of anomalous pulmonary veins.

Partial anomalous pulmonary venous connection (PAPVC) is an extremely rare congenital condition where one or more of the pulmonary veins are connected to the venous circulation. Although initially suspected with unexplained right ventricular enlargement on transthoracic echocardiography (TTE), cardiac MRI is able to delineate the anatomical variant. We present a case of a 65-year-old male diagnosed with left sided PAPVC using multimodality cardiac imaging.