The clinical outcome and risk factors of phospholipase A2 receptor-associated idiopathic membranous nephropathy in adults / 中华肾脏病杂志

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults,as well as to explore the potential prognostic factors.Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected.Results PLA2R-associated IMN patients accounted for 89.2％ of the IMN patients.Spontaneous remission occurred in 35.5％ of PLA2R-associated IMN patients.The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P ＜ 0.05).Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060,95％CI 0.007-0.493,P=0.009),while higher serum albumin at baseline (OR=1.480,95％ CI 1.144-1.932,P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040,95％CI 1.322-3.151,P=0.001) were independent protective factors for spontaneous remission.About 42.1％ PLA2R-associated IMN patients had received immunosuppressive therapy,with induced remission rate being 70.7％.High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268,95％ CI 1.014-1.585,P=0.038).Conclusions PLA2R-associated IMN accounts for most of the IMN patients,with a spontaneous remission rate of 35.5％,during the follow-up period,which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer.Induced remission rate is 70.7％ in patients in need of immunosuppresants.The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.

Chronic metabolic acidosis markedly induces proliferation of mesangial cells in rats / 中国病理生理杂志

AIM: To study the effects of chronic metabolic acidosis on glomerulus, mesangial cells and the production of extracellular matrix. METHODS: Chronic metabolic acidosis was induced by addition of 0.28 mol/L NH_4Cl to drinking water for 3, 7, or 14 days in male Wistar rats (n=10). Light microscope combined with computer software (Motic Images Advanced 3.2) was used to determine the effect of chronic acid loading on renal morphologic changes. The expressions of proliferation cell nuclear antigen (PCNA) and p27 in glomeruli were detected by Western blotting or immunohistochemistry. Fibronectin (FN) mRNA was detected by real-time PCR. The proliferation of mesangial cells in vitro was determined by ~3H:-TdR incorporation. The concentration of FN in cultured supernatant was detected by ELISA. RESULTS: On day 1, 3, 7 and 14, the arterial pH and plasma HCO_3~-: in experimental rats were significantly decreased. There was a significantly increased in the kidney weight and the ratio of kidney to body weigh in experimental rats on day 3, 7 and 14. The glomerular area and cell numbers also increased significantly. Immunoblotting demonstrated decreased p27 expression and increased PCNA expression in isolated glomeruli, and the expression of PCNA increased in a time-dependent manner following the time of chronic metabolic acidosis. Immunohistochemistry showed increased positive PCNA expression mainly localized to mesangial cells. The expression of FN mRNA was significantly elevated in experimental rats on day 7 and 14. In vitro, acid loading induced mesangial cell proliferation and synthesis of FN. CONCLUSION: These results suggest that chronic metabolic acidosis induces mesangial cell proliferation, and its mechanism may be associated with the downregulation of cell cycle kinase inhibitor p27.

Ameliorative effect of adrenalectomy on remnant nephropathy in the rat depends on aldosterone level / 中华肾脏病杂志

4-fold elevation in renal cortex in plasma aldosterone as compared to those of the SHAM rats. The above pathologies were markedly improved in bi-ectomised rats with significantly lower aldosterone level. Being constantly infused exogenous aldosterone, bi-ectomized rats manifested greater proteinuria, hypertension, glomerulosclerosis and increased level of TGF-?1 compared to bi-ectomised rats. Indeed, these features were similar in exogenous aldosterone rats and 5/6 nephrectomized rats. Furthermore, the expression of mineralocorticoid receptor (MR) mRNA was remarkablely enhanced in SNX group and was decreased in ADX group. However, the mRNA expression of 11 ?-hydroxysteroid dehydrogenase II (11?-HSD2) in each group was opposite to that of MRmRNA. Ccr and kidney/body weight showed no differences among four experimental groups. Conclusion Aldosterone contributes to the progression of ablative nephropathy in the rat through mechanisms other than systolic blood pressure.

Treatment with antisense Smad2 oligodeoxynudeotides reduces extracellular matrix secretion in rat mesangial cells cultured with high glucose / 中华肾脏病杂志

Objective To investigate the effects of antisense Smad2 oligodeoxynudeotides(ODN) on fibronetin(FN) and collagen Ⅳ(ColⅣ) secretion of rat mesangial cells cultured with high glucose, explore the action of Smad2 in the glomerulosclerosis and to find a new method to retard the progress of glomerular fibrosis. Methods 20-mer antisense, sense and random ODNs were designed and synthesized that were phosphorothioate modified to increase stability. The antisense ODN encompassed the ATG of the rat Smad2 gene. ODN was tranferred transiently into rat mesangial cells through liposome. Rat cells were treated with high glucose. mRNA and protein of Smad2 were detected by RT-PCR and cytochemistry. FN and ColⅣ were examined by ELISA. Results Antisense ODN significantly decreased mRNA and protein expression of Smad2 in rat mesangial cells treated with high glucose(P