Macrophage Ontogeny, Phenotype, and Function in Ischemia Reperfusion-Induced Injury and Repair.

AKI is characterized by a sudden, and usually reversible, decline in kidney function. In mice, ischemia-reperfusion injury (IRI) is commonly used to model the pathophysiologic features of clinical AKI. Macrophages are a unifying feature of IRI as they regulate both the initial injury response as well as the long-term outcome following resolution of injury. Initially, macrophages in the kidney take on a proinflammatory phenotype characterized by the production of inflammatory cytokines, such as CCL2 (monocyte chemoattractant protein 1), IL-6, IL-1 ß , and TNF- α . Release of these proinflammatory cytokines leads to tissue damage. After resolution of the initial injury, macrophages take on a reparative role, aiding in tissue repair and restoration of kidney function. By contrast, failure to resolve the initial injury results in prolonged inflammatory macrophage accumulation and increased kidney damage, fibrosis, and the eventual development of CKD. Despite the extensive amount of literature that has ascribed these functions to M1/M2 macrophages, a recent paradigm shift in the macrophage field now defines macrophages on the basis of their ontological origin, namely monocyte-derived and tissue-resident macrophages. In this review, we focus on macrophage phenotype and function during IRI-induced injury, repair, and transition to CKD using both the classic (M1/M2) and novel (ontological origin) definition of kidney macrophages.

Future risk of diabetes among Indians with metabolic and phenotypic obesity: Results from the 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES-158).

AIM: To investigate the risk of type 2 diabetes (T2DM) among the combinations of BMI categories and metabolic syndrome in Asian Indians. MATERIALS AND METHODS: Individuals from the Chennai Urban Rural Epidemiology Study cohort (n = 1,368), free of diabetes at baseline were stratified by BMI and metabolic health as metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically obese non-obese (MONO) and metabolically obese obese (MOO). Phenotypic obesity was defined as BMI ≥ 25 kg/m2 and metabolic obesity as presence of any two of the metabolic abnormalities: hyperglycemia, high blood pressure, high triglyceridemia or low HDL cholesterol. Hazard ratios for progression to diabetes were estimated using Cox proportional hazard regression. RESULTS: During median 9.1 years of follow-up, incident cases of diabetes were highest among MOO-45.1%, followed by MONO-41.3%, MHO-27.1% and MHNO-15.9%. Incidence rates of diabetes among MOO, MONO, MHO and MHNO were 57.8, 50.9, 30.4 and 18.1 per 1000 person years, respectively. Hazard ratio for diabetes development were 1.71 in MHO, 2.87 in MONO, and 3.39 in MOO compared with MHNO. CONCLUSIONS: Increased BMI and metabolic risk factor clustering independently contribute to the increased risk of T2DM in obese individuals. Screening for metabolic abnormalities should be performed routinely in clinic to identify high-risk individuals and institute appropriate preventive measures.