Chitosan (CS) is an effective clarifying agent for fruit juice. However, its low antioxidant ability is a limitation in preserving the antioxidant capacity of the juice during clarification. In this ...work, an antioxidant CS derivative, tannic acid-modified CS (TA-CS), was used as a clarifying agent to optimise the clarification of kiwifruit juice. By using response surface methodology and the transmittance of the juice as a response, the optimal clarification conditions were obtained as follows: TA-CS concentration of 600 μg mL−1, juice pH of 3.5, and heating temperature of 70 °C. Under the optimal conditions, TA-CS showed an excellent clarification effect on kiwifruit juice, which was confirmed by the high transmittance of 99.3%. Meanwhile, the retention rate of vitamin C in the juice reached 97.0% for the TA-CS treatment, being significantly higher than that for the CS treatment. Our results suggest that TA-CS may be a promising clarifying agent for the production of fruit juice.
Transforming growth factor β (TGF-β) induces the process of epithelial-mesenchymal transition (EMT) through the Smad and JNK signaling. However, it is unclear how these pathways interact in the ...TGF-β1-induced EMT in rat peritoneal mesothelial cells (RPMCs). Here, we show that inhibition of JNK activation by introducing the dominant-negative JNK1 gene attenuates the TGF-β1-down-regulated E-cadherin expression, and TGF-β1-up-regulated α-SMA, Collagen I, and PAI-1 expression, leading to the inhibition of EMT in primarily cultured RPMCs. Furthermore, TGF-β1 induces a bimodal JNK activation with peaks at 10 minutes and 12 hours post treatment in RPMCs. In addition, the inhibition of Smad3 activation by introducing a Smad3 mutant mitigates the TGF-β1-induced second wave, but not the first wave, of JNK1 activation in RPMCs. Moreover, the inhibition of JNK1 activation prevents the TGF-β1-induced Smad3 activation and nuclear translocation, and inhibition of the TGF-β1-induced second wave of JNK activation greatly reduced TGF-β1-induced EMT in RPMCs. These data indicate a crosstalk between the JNK1 and Samd3 pathways during the TGF-β1-induced EMT and fibrotic process in RPMCs. Therefore, our findings may provide new insights into understanding the regulation of the TGF-β1-related JNK and Smad signaling in the development of fibrosis.
Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this ...condition. To identify risk factors and develop a prediction model, we assessed data from patients ≥ 14 years old with crescentic IgAN who were followed ≥ 12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3 ± 3.4 mg/dl, and the mean percentage of crescents was 66.4%± 15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%± 4.7%, 45.8%± 5.1%, and 30.4%± 6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio HR, 1.32; 95% confidence interval CI, 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.
Background: The COVID-19 pandemic is challenging healthcare systems worldwide and has placed hospitals and healthcare providers (HCPs) at the center of a global crisis. Disruptions to hospital ...priorities, and limitations placed on the mobility of societies, have contributed to changes in the way HCPs and patients view and access dialysis for kidney failure, including which dialysis modality is preferred. Summary: This article explores the dialysis experience within the COVID-19 pandemic environment in the Asia Pacific region and presents evidence that peritoneal dialysis (PD) provides benefits to patients, HCPs, and health systems. As the number of people infected with COVID-19 has increased, the advantages of PD as a dialysis modality for limiting the spread of COVID-19 infection has been recognized. Key Message: The utility of PD has been demonstrated during the COVID-19 pandemic; thus, ensuring that the usage of PD is maintained and increased in a post-pandemic future is key. Such a scenario could enhance our ability to care for patients without interruption in circumstances of unforeseen obstacles and supports the ability of healthcare systems and patients to overcome barriers to dialysis access.
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•Sodium glucose cotransporter-2 was found in both the human peritoneum and peritoneal mesothelial cells.•Sodium glucose cotransporter-2 inhibitors reduced the glucose uptake and ...increased ultrafiltration through the peritoneum.
Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been widely used in the clinic to reduce blood glucose levels by enhancing glucose excretion. However, whether such agents might also reduce glucose absorption via the peritoneal function of human peritoneal mesothelial cells (HPMCs) that also express SGLT-2 is not clear.
An acute peritoneal dialysis (PD) model in nonuremic rats was established. Ratios of peritoneal glucose uptake at D4/D0 of Sprague-Dawley rats treated with the SGLT-2 inhibitor, empagliflozin were tested to evaluate the effect of this inhibitor on peritoneal glucose absorption. An in vitro model of HPMCs obtained from peritoneal dialysate effluent in patients undergoing PD was used. HPMCs were exposed to high glucose (60 mM) in the presence and absence of empagliflozin. Glucose uptake and glucose consumption, which were used to estimate the activity of SGLT-2 in HPMCs, were measured by flow cytometry and hexokinase respectively. The expression of SGLT-2 in both peritoneum and HPMCs was also observed by real-time polymerase chain reaction (PCR), western blot, and immunofluorescence staining.
Both ratios of peritoneal glucose uptake at D4/D0 and ultrafiltration of rats treated with 3 mg kg−1 of empagliflozin for 3 days increased significantly compared to those of the control group (0.32 ± 0.40 vs. 0.11 ± 0.11 mM, P = 0.001；17.00 ± 3.58 vs. -13.67 ± 17.25 ml, P = 0.002). Compared to the control group, the expression of mRNA and protein in SGLT-2 increased significantly in the rats treated with 3 mg kg−1 of empagliflozin for 3 days. Both glucose consumption and uptake of HPMCs incubated with 1 μM of empagliflozin for 24 h decreased significantly compared to control values (8.69 ± 1.77 vs. 11.48 ± 1.00 mM, P = 0.004; 31.97 ± 4.81 vs. 43.98 ± 1.38, P = 0.002).
An SGLT-2 inhibitor was able to exert a glucose-lowering effect in peritoneum exposed to PD solution by inhibiting the activity of SGLT-2.
The effect of fluid overload and variation on residual renal function (RRF) in peritoneal dialysis (PD) patients is controversial.
Retrospective cohort study was designed. One-hundred and ninety PD ...patients with measured glomerular filtration rate (mGFR) ≧ 3 ml/min/1.73 m2 were recruit. Fluid status of every participant was assessed by bioelectrical impedance analysis (BIA) every 3 months for 1 year. The cohort was divided into three hydration groups, namely persistent overhydration (PO) group, intermittent overhydration (IO) group and normal hydration (NH) group. Additionally, participants were also divided into high or low fluid variation groups. The decline rate of RRF and the event of anuria were followed up for 1 year. The association of fluid overload with RRF loss was evaluated by Cox proportional hazard models adjusted for confounders.
Thirty-six (18.9%) patients developed anuria. The decline rate of mGFR in both PO and IO groups were significantly faster than that of NH group (PO vs NH: -0.2 vs -0.1 ml/min/1.73 m2/month, p < 0.01; IO vs NH: -0.2 vs -0.1 ml/min/1.73 m2/month, p < 0.01). Kaplan-Meier analysis showed poorer RRF outcome in both PO and IO groups compared with that of NH group (PO vs NH: p < 0.001; IO vs NH: p = 0.006). Patients with high fluid variation had worse RRF survival than those with low fluid variation (p = 0.04). Adjusted Cox regression models indicated the hazard ratio of RRF loss in PO group was 8.90-folds higher (95% confidence interval 3.07-31.89) than that in NH group.
These findings suggested fluid overload was independently associated with the decline of RRF in PD patients.
IgA nephropathy (IgAN) is the most common primary glomerular disease in China and worldwide. The proliferation of B cells is known to be associated with both risk and prognosis of IgAN, but the ...epigenetic mechanism underlying this association is unknown. In this study we carried out the first Epigenome-wide Association Study (EWAS) by using the latest Infinium Methylation EPIC BeadChip on 184 B cell-specific samples (92 case/control pairs) for Chinese IgAN population. After rigorous data normalization and residual batch effect correction, linear mixed effect model was used to detect methylation CpG sites associated with IgAN adjusting for age, gender and smoking. False discovery rate (FDR) less than 10% was used to account for multiple testing. Weighted gene co-methylation networks were generated to identify gene modules highly correlated with IgAN. A permutation test was performed to account for the potential effect of overfitting. After adjusting clinical covariates and potential technical batch effects, three CpGs corresponding to PCDH17, TERT, WDR82 genes and three in the intergenic regions passed the genome-wide significant threshold. Methylation network analysis identified an additional IgAN associated gene module, containing 72 significant CpGs including GALNT6, IQSEC1, CDC16 and SYS1, involved in the pathway related to tubular atrophy/interstitial fibrosis of IgAN. These results suggested important DNA methylation and gene targets in CD19
+
B cells for the pathogenesis of IgAN.
Abstract
Background and Aims
Hyperphosphatemia in chronic kidney disease (CKD) patients is associated with adverse outcomes, including vascular calcification, increasing risks of disease progression ...and even death. Sevelamer carbonate have been approved in Europe for phosphate lowering treatment in pre-dialysis CKD patient, its efficacy and safety in Chinese CKD hyperphosphatemia patients are not previously reported.
Method
This was a phase III, multi-center, randomized, double blind, placebo-controlled, balanced (1:1, sevelamer: placebo) parallel-group study to evaluate the efficacy and safety of sevelamer carbonate versus placebo over 8 weeks’ duration in hyperphosphatemic CKD patients not on dialysis in China (Registration number NCT03001011). The primary objective of this study is to demonstrate efficacy of sevelamer carbonate tablets in the reduction of serum phosphorus in hyperphosphatemia in patients with chronic kidney disease (CKD) not on dialysis.
Results
In all, 202 patients were randomized (sevelamer, n=101; placebo, n=101); mean age was 50.7 years, 53.5% were male and the mean time of CKD diagnosis was 3.4 years with mean eGFR 7.5 ml/min/1.73 m2. The baseline phosphorous were 2.13±0.35 mmol/L and 2.12±0.37 mmol/L in sevelamer and placebo group, respectively. The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate (-0.22±0.47 mmol/L) compared with placebo (0.05±0.44 mmol/L) (mean difference between sevelamer carbonate and placebo was -0.26 mmol/L, P<0.0001). When compared with placebo, sevelamer carbonate significantly reduced serum total cholesterol (-0.90±0.85 vs. -0.06±0.68 mmol/L, P<0.0001), low-density lipoprotein cholesterol (-0.94±0.72 vs. -0.04±0.58 mmol/L, P<0.0001) and calcium-phosphorous product (-0.48±0.97 vs. 0.05±0.81 mmol2/L2) from baseline to week 8. Serum iPTH was not significantly changed in sevelamer carbonate group compared with placebo group (-9.60±136.00 vs. 7.61±141.92 ng/L, P=0.83). Sevelamer carbonate was well tolerated with 83.27% compliance compared with 82.19% compliance in placebo arm. Average dose of sevelamer carbonate was 7.51 g/d at the end of study and 4.52 g/d across the study. Adverse events experienced by patients in sevelamer carbonate and placebo group were similar.
Conclusion
This study demonstrated that sevelamer carbonate has produced a significant reduction of serum phosphorous, and is safe and tolerated in Chinese pre-dialysis CKD patients with hyperphosphatemia.
The aim of this study was to investigate the prevalence of coexisting frailty and cognitive impairment and its association with clinical outcomes in patients on continuous ambulatory peritoneal ...dialysis (CAPD). Patients on CAPD started to enroll from 2014 to 2016 and ended follow-up by 2017. Frailty was assessed by clinical frailty scale (CFS), and cognitive function was assessed by Montreal Cognitive Assessment (MoCA). Totally 784 CAPD patients were recruited, with median duration of PD 30.7 (8.9~54.3) months. The mean age was 48.8 ± 14.6 years, 320 (40.8%) patients were female and 130 (16.6%) had diabetic nephropathy. Patients with cognitive impairment were more than those with frailty (55.5% vs. 27.6%). Coexisting frailty and cognitive impairment was present in 23.9% patients. Pathway analysis showed that CFS score was negatively associated with MoCA score (β = -0.69, P < 0.001). Coexisting frailty and cognitive impairment was associated with decreased patient survival rate (Log-rank = 84.33, P < 0.001) and increased peritonitis rate (0.22 vs. 0.11, 0.15 and 0.12 episodes per patient year, respectively; all P < 0.001). It was concluded that there was a relatively high prevalence of coexisting frailty and cognitive impairment among patients on CAPD. Frailty was positively associated with cognitive impairment. Coexisting frailty and cognitive impairment increased the risk of adverse outcomes.
Abstract Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate ...the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5 mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10 mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes.
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