Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin

Vascular endothelial activation, marked by de novo expression of E-selectin, is an early and essential event in the process of leukocyte extravasation and inflammation. Evidence suggests that hepatocyte growth factor (HGF) ameliorates inflammation in animal models of renal disease, implying that HGF might inhibit specific components of the inflammatory response. This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. HGF activated phosphatidylinositol 3-kinase (PI3K)–Akt that in turn inhibited its downstream transducer glycogen synthase kinase (GSK)3. Blockade of the PI3K–Akt pathway with specific inhibitors abrogated HGF induced inhibitory phosphorylation of GSK3 and suppression of E-selectin. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. Moreover, ectopic expression of an uninhibitable mutant GSK3β, in which the regulatory serine-9 is replaced by alanine, abolished HGF's suppressive effect on endothelial E-selectin. In vivo, administration of exogenous HGF reduced endothelial expression of E-selectin induced by bolus injection of TNF-α. This was associated with less sequestration of circulating fluorescence-labeled macrophages in the kidney. These findings suggest that HGF ameliorates acute renal inflammation in part by downregulating E-selectin mediated macrophage adhesion to the inflamed endothelium

PowerPoint Slides for: Medical Neighborhood Model for the Care of Chronic Kidney Disease Patients

<i>Background:</i> The patient-centered medical home is a popular model of care, but the patient-centered medical neighborhood (PCMN) is rarely described. We developed a PCMN in an academic practice to improve care for patients with chronic kidney disease (CKD). The purpose of this study is to identify the prevalence of CKD in this practice and describe baseline characteristics, develop an interdisciplinary team-based approach to care and determine cost associated with CKD patients. <i>Methods:</i>Patients with CKD stage 3a with comorbidities through stage 5 were identified. Data collected include demographics, comorbidities and whether patients had a nephrologist. Using a screening tool based on the 2012 Kidney Disease Improving Global Outcomes guidelines, a nurse care manager (NCM) made recommendations about management including indications for referral. A pharmacist reviewed patients' charts and made medication-related recommendations. Blue Cross Blue Shield (BCBS) insurance provided cost data for a subset of patients. <i>Results:</i> A total of 1,255 patients were identified. Half did not have a formal diagnosis of CKD and three-quarters had never seen a nephrologist. Based on the results of the screening tool, the NCM recommended nephrology E-consult or full consult for 85 patients. The subset of BCBS patients had a mean healthcare cost of $1,528.69 per member per month. <i>Conclusions:</i> We implemented a PCMN that allowed for easy identification of a high-risk, high-cost population of CKD patients and optimized their care to reflect guideline-based standards

Supplementary Material for: Medical Neighborhood Model for the Care of Chronic Kidney Disease Patients

<p><b><i>Background:</i></b> The patient-centered medical home is a popular model of care, but the patient-centered medical neighborhood (PCMN) is rarely described. We developed a PCMN in an academic practice to improve care for patients with chronic kidney disease (CKD). The purpose of this study is to identify the prevalence of CKD in this practice and describe baseline characteristics, develop an interdisciplinary team-based approach to care and determine cost associated with CKD patients. <b><i>Methods:</i></b> Patients with CKD stage 3a with comorbidities through stage 5 were identified. Data collected include demographics, comorbidities and whether patients had a nephrologist. Using a screening tool based on the 2012 Kidney Disease Improving Global Outcomes guidelines, a nurse care manager (NCM) made recommendations about management including indications for referral. A pharmacist reviewed patients' charts and made medication-related recommendations. Blue Cross Blue Shield (BCBS) insurance provided cost data for a subset of patients. <b><i>Results:</i></b> A total of 1,255 patients were identified. Half did not have a formal diagnosis of CKD and three-quarters had never seen a nephrologist. Based on the results of the screening tool, the NCM recommended nephrology E-consult or full consult for 85 patients. The subset of BCBS patients had a mean healthcare cost of $1,528.69 per member per month. <b><i>Conclusions:</i></b> We implemented a PCMN that allowed for easy identification of a high-risk, high-cost population of CKD patients and optimized their care to reflect guideline-based standards.</p