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Ai-Hua Zhang,1 Guang-Xia Dai,2 Qi-Dong Zhang,1 Hong-Dong Huang,1 Wen-Hu Liu1 1Nephrology Department, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, People’s Republic of China; 2Endocrinology Department, Beijing Nanyuan Hospital, Beijing, People’s Republic of ChinaCorrespondence: Hong-Dong Huang; Wen-Hu Liu, Nephrology Department, Capital Medical University Affiliated Beijing Friendship Hospital, No. 95 Yong An Road, Xi Cheng District, Beijing, 100050, People’s Republic of China, Tel +86-10 63138579, Fax +86-10 63139144, Email huangHD201902@163.com; l13901163354@163.comBackground: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response.Methods: One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥ 30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end.Results: The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer–Lemeshow test: χ2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000– 1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999– 1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer–Lemeshow test: χ2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22– 0.31) vs 0.18 (0.13– 0.22), P = 0.012).Conclusion: PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.Keywords: membranous nephropathy, peripheral blood cell ratios, platelet-lymphocytes ratio, monocyte–lymphocyte ratio, treatment response, outcome

Introduction: Apoptosis of vascular smooth muscle cells induced by hyperphosphatemia is a critical mechanism of chronic kidney disease-related vascular disorders. The present study investigated whether extracellular calcium-sensing receptor (CaSR) regulates stanniocalcin 2 (STC2) expression in HAoSMCs and subsequently protects HAoSMCs from high-phosphate-induced apoptosis. Methods: HAoSMCs were cultured, and STC2 expression was determined by qPCR. A calcimimetic (NPS R-568) or calcilytic (NPS-2143) was applied to HAoSMCs. STC2 mRNA and protein levels were measured by qPCR and Western blot, respectively, and confocal microscopy was employed to investigate subcellular localization. STC2 overexpression and silencing were induced to assess the effects of STC2 on high-phosphate-induced apoptosis, which was determined by caspase-3 levels and TUNEL staining. The anti-apoptotic effect of CaSR-induced STC2 was confirmed by interfering with STC2 expression in the presence of NPS R-568. Results: The constitutive expression of STC2 was confirmed. STC2 mRNA and protein levels were increased by NPS R-568 with or without high phosphate. NPS-2143 resulted in decreased STC2 mRNA levels, but decreased STC2 protein levels were only found under the high-phosphate condition. Confocal microscopy demonstrated the colocalization of STC2 and plasma membrane or endoplasmic reticulum markers. STC2 overexpression reduced HAoSMCs apoptosis, which were reversed with STC2 silencing. NPS R-568 treatment reduced HAoSMCs apoptosis, but STC2 silencing abolished the protective effect. Conclusion: This is the first evidence that STC2 is regulated by CaSR in HAoSMCs. CaSR activation-induced STC2 has putative anti-apoptotic effects against high phosphate. Calcimimetics are promising agents to treat uremic vascular injury.

Background Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients still continue to progress and worsen and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN in adults, the clinical features don’t often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response in patients with PMN. Methods In this study, 118 patients with PMN were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up visit. Renal outcome endpoint was defined as 50% or more Cr increase at the end. Results The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). Especially for patients with CR or not, the difference was near to statistic significant (P=0.095). It is noteworthy that when analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ2=8.328, P=0.402; OR (PLA2R Ab titer) =1.002 (95% CI 1.000-1.004, P=0.042); OR (PLR) =1.006 (95% CI 0.999-1.013, P=0.098) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ2=13.885, P=0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P=0.012). Conclusion PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.

Vascular calcification (VC) and myocardial hypertrophy are very common in patients on hemodialysis (HD). Previous studies have only assessed the cross-sectional associations of VC with left ventricular mass (LVM) and the predictive value of individual factors. The present study investigated the relationship between abdominal aortic calcification (AAC) and LVM increment over time, and the combined effect of these factors on the outcomes of HD patients. 104 HD patients were enrolled. AAC scores were evaluated on left lateral lumbar spine radiographs. Echocardiography was performed to calculate the LVM changes during a 2-year period. At baseline, 91 patients (87.5%) had varying degrees of AAC (median score 6.0, range 2.0 - 11.0). After 2 years, the mean LVM change was 7.49 g (range -5.03 - 26.00 g), and 68 patients (65%) had an increased LVM. Patients with higher baseline AAC scores had significantly larger LVM and LVM index increments. Patients with increased LVM had significantly higher baseline AAC scores and hemoglobin, serum phosphate, and hypersensitive C-reactive protein levels. Multiple stepwise linear regression demonstrated that the baseline AAC was the only independent predictor of increased LVM after 2 years. 28 patients (26.9%) died in the subsequent 5 years. Patients with lower baseline AAC scores had a significantly higher cumulative survival rate than those with higher AAC scores. However, the LVM change (either alone or in combination with the AAC score) had no significant effect on survival. In conclusion, AAC is an independent predictor of LVM increase over time in HD patients. Prevention and treatment of VC may be a promising intervention target to improve left ventricular remodeling and outcomes in HD patients.

Background: Alcohol abuse resulted in high prevalence of alcoholic cardiac and hepatic disorders. Any agent(s) with the bio-activities to suppress mitochondrial apoptotic pathway, and attenuate apoptotic and oxidative stresses might be able to protect cardiac and hepatic cells against ethanol. Objective(s): Phytochemical composition of aqueous extract prepared from steamed daylily flower (DAE) was determined. The protective effects of DAE for H9c2 and L-02 cells against ethanol were evaluated. Materials and Methods: The amount of total phenolic acids, total flavonoids, total anthocyanins and total triterpenoids in DAE was analyzed. H9c2 or L-02 cells were first treated with 0.25, 0.5 or 1% DAE, and followed by 150 mM ethanol exposure. Results: Results: The amount of total phenolic acids, flavonoids, anthocyanins and triterpenoids in DAE was in the range of 1219-2045 mg/100 g dry weight. DAE treatments at 0.5 and 1% increased the viability of H9c2 cells, but at three test concentrations enhanced the survival of L-02 cells. DAE at 0.5 and 1% up-regulated Bcl-2 mRNA expression, down-regulated Bax mRNA expression, decreased Bax/Bcl-2 ratio, and lowered caspase-3 activity in both cell lines. Ethanol increased reactive oxygen species level, decreased glutathione content, and glutathione peroxidase and catalase activities in both cell lines. DAE at test concentrations reversed these changes in both cell lines. DAE at 0.5 and 1% reduced cytochrome P450 2E1 and NADPH oxidase activities, and lowered p47phox mRNA expression. However, DAE at three test concentrations decreased gp91phox mRNA expression in both cell lines. DAE at 0.5 and 1% up-regulated factor E2-related factor 2 and heme oxygenase-1 mRNA expression in both cell lines. Conclusions: These results suggested that this aqueous extract might be a potent function food supplement to benefit heart and liver against ethanol induced injury.