Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P,0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albuminto-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.

The progressive loss of cardiomyocytes caused by cell death leads to cardiac dysfunction and heart failure (HF). Rapamycin has been shown to be cardioprotective in pressure-overloaded and ischemic heart diseases by regulating the mechanistic target of rapamycin (mTOR) signaling network. However, the impact of rapamycin on cardiomyocyte death in chronic HF remains undetermined. Therefore, in the current study we addressed this issue using a rat myocardial infarction (MI)-induced chronic HF model induced by ligating the coronary artery. Following surgery, rats were randomly divided into six groups, including the sham-, vehicle- and rapamycin-operated groups, at 8 or 12 weeks post-MI. A period of 4 weeks after MI induction, the rats were treated with rapamycin (1.4 mg-kg-day) or vehicle for 4 weeks. Cardiac function was determined using echocardiography, the rats were subsequently euthanized and myocardial tissues were harvested for histological and biochemical analyses. In the cell culture experiments with H9c2 rat cardiomyocytes, apoptosis was induced using angiotensin II (100 nM; 24 h). Cardiomyocyte apoptosis and autophagy were assessed via measuring apoptosis- and autophagy-associated proteins. The activities of mTOR complex 1 (mTORC1) and mTORC2 were evaluated using the phosphorylation states of ribosomal S6 protein and Akt, respectively. The activity of the endoplasmic reticulum (ER) stress pathway was determined using the levels of GRP78, caspase-12, phospho-JNK and DDIT3. Echocardiographic and histological measurements indicated that rapamycin treatment improved cardiac function and inhibited cardiac remodeling at 8 weeks post-MI. Additionally, rapamycin prevented cardiomyocyte apoptosis and promoted autophagy at 8 weeks post-MI. Rapamycin treatment for 4 weeks inhibited the mTOR and ER stress pathways. Furthermore, rapamycin prevented angiotensin II-induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. These results demonstrated that rapamycin reduced cardiomyocyte apoptosis and promoted cardiomyocyte autophagy, by regulating the crosstalk between the mTOR and ER stress pathways in chronic HF.

BackgroundThe awareness, treatment and control of diabetes mellitus (DM) can effectively reflect on the social status of diabetes conditions. Although several researchers have investigated the awareness, treatment and control rates of diabetes mellitus in China, little is known about their association with risk factors. This study aims to examine the relationship between risk factors and awareness, treatment and control of diabetes mellitus in northeast China.MethodsA cross-sectional survey was conducted in 2012. Multistage stratified random cluster sampling design was used to select participants aged 18 to 79 years old. The analysis was based on a representative sample of 1,854 adult subjects. Multivariable logistic regression analysis was used to examine socio-demographic factors associated with the levels of awareness, treatment and control of diabetes mellitus.ResultsThe awareness, treatment, and control rates of diabetes mellitus were 64.1%, 52.9% and 44.2%, respectively. In the multivariable logistic regression analysis, family history of diabetes was significantly positively associated with awareness (OR, 2.145; 95% CI, 1.600–2.875) and treatment (OR, 2.021; 95% CI, 1.559–2.619) of diabetes mellitus, while negatively associated with control (OR, 0.671; 95% CI, 0.529–0.951). Cigarette smokers and alcohol drinkers were less likely than non-smokers and non-drinkers to be aware of their blood glucose levels (OR, 0.895, 0.614; 95% CI, 0.659–1.216, 0.446–0.844, respectively). Participants who frequently exercise were more likely to be aware of their diabetic conditions than people who never or rarely exercise (OR, 2.003; 95% CI, 1.513–2.651).ConclusionsWe found that the awareness and treatment of diabetes mellitus were positively associated with age and were high in participants with a family history of diabetes and those who exercise frequently, but low for cigarette smokers and alcohol drinkers. Participants with a family history of diabetes had their diabetic condition poorly controlled.

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