Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

The predictive effect of combining MEST with clinical data at biopsy on renal survival outcomes has not been investigated in patients with IgA nephropathy (IgAN). MEST of The Oxford classification of IgAN and 24-hour urine proteinuia measured at enrollment. The primary outcome was a composite of either ESRD (eGFR to <15 ml/min per 1.73 m2), or a permanent reduction in eGFR to below 50% of the value at biopsy. 742 patients were enrolled and follow-up >3 years, and were divided into two groups according to eGFR levels at biopsy. Multivariable logistical regression revealed that proteinuria at biopsy (OR 5.307 (95% Cl 3.003 to 9.376) p = 0.000), tubular atrophy/interstitial fibrosis scores (T) in MEST (OR 3.915 (95%Cl 2.710 to 5.654) p = 0.000) were the two predictors of eGFR decline for IgAN patients. Kaplan–Meier survival curves show significant difference in renal survival outcome among each T scores groups at biopsy (T0, T1, T2) (P < 0.05) and proteinuria levels at biopsy (P < 0.05), individially. Patients with T2 combined proteinuria at biopsy have the worst renal survival outcome. In conclusion, T scores in MEST classification combined with proteinuria at biopsy could be one of the important early predictors for the renal survial outcomes in patients with IgAN.

Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

BackgroundSerum uric acid (UA) has been reported as a risk factor for type 2 diabetes mellitus (T2DM). However, whether serum UA is associated with insulin resistance and insulin secretion, and the effect of gender on it in the case of the existed association, both remain undefined.MethodsA cross-sectional study was designed and performed, which enrolled a total of 403 newly diagnosed T2DM patients (mean age, 50.21 ± 13.34 years (62.5% males)). Clinical characteristics and islet function indexes of all participants were analyzed based on gender-specific tertiles of serum UA levels. In addition, multiple linear regression analysis was conducted to investigate covariates associated with islet function indexes.ResultsThe mean levels of serum UA were 331.05 μmol/L (interquartile range (IQR): 60.6, 400.9 μmol/L) and 267.9 μmol/L (IQR: 204.7, 331.9 μmol/L) in men and women, respectively. The values of insulin secretion indexes involving AUCins30/glu30, AUCins120/glu120 and total insulin disposition index (DI120) in females were significantly higher than those in males. Apart from the homeostasis model assessment insulin resistance of men, serum UA was positively associated with insulin secretion and insulin resistance indexes both in men and women. Multivariable linear regression analysis showed serum UA exerted an independent impact on insulin secretion in females, but not on insulin resistance. In males, islet function was simultaneously affected by serum UA age, body mass index (BMI), and serum lipids.ConclusionSerum UA harbored a positive correlation with insulin secretion and insulin resistance indexes in newly diagnosed T2DM patients, which was influenced by gender, BMI, serum lipids. Hence, serum UA may be considered as a predictor for islet function in clinical practice.

A novel strategy for the direct carboxyl transfer involving a decarboxylative A 3 reaction of α-keto acids, primary amines, and alkynes has been developed under a Cu(I)/Cu(II) binary catalysis system. This multicomponent reaction provides a facile and efficient approach for the production of a diverse range of 2oxazolidinones in moderate to excellent yields through a one-pot CO 2 elimination−fixation procedure. The conciseness of the "CO 2 recycling" process makes this ideal synthesis superior over classical CO 2 utilization.

No abstract

No abstract

The choice of distribution is often made on the basis of how well the data appear to be fitted by the distribution. The inverse Gaussian distribution is one of the basic models for describing positively skewed data which arise in a variety of applications. In this paper, the problem of interest is simultaneously parameter estimation and variable selection for joint mean and dispersion models of the inverse Gaussian distribution. We propose a unified procedure which can simultaneously select significant variables in mean and dispersion model. With appropriate selection of the tuning parameters, we establish the consistency of this procedure and the oracle property of the regularized estimators. Simulation studies and a real example are used to illustrate the proposed methodologies.