Serpin E1 mediates the induction of renal tubular degeneration and premature senescence upon diabetic insult.

As a leading cause of chronic kidney disease, diabetic kidney disease (DKD) involves insidious but progressive impairments of renal tubules, and is associated with premature renal aging. The underlying pathomechanisms remain elusive. Post hoc analyses of the publicly-available renal transcriptome revealed that TGFß1 is overexpressed in renal tubulointerstitia in patients with DKD and positively correlated with kidney aging signaling. This finding was validated in kidney biopsy specimens collected from patients with DKD, associated with renal tubular senescence and degenerative changes. In vitro in renal tubular epithelial cells, exposure to a diabetic milieu, stimulated with high ambient glucose and TGFß1, elicited premature senescence, as evidenced by staining for senescence-associated ß-galactosidase activity and increased expression of p16INK4A, and p53. This coincided with Serpin E1 induction, in parallel with increased fibronectin accumulation and reduced expression of the epithelial marker E-cadherin, all indicative of degenerative changes. Reminiscent of the action of typical senolytics, a small molecule inhibitor of Serpin E1 substantially mitigated the pro-senescent and degenerating effects of the diabetic milieu, suggesting an essential role of Serpin E1 in mediating renal tubular senescence upon diabetic insult. Moreover, inhibition of Serpin E1 abolished the diabetic insult-triggered paracrine senescence of renal tubular cells. In consistency, in patients with DKD, renal tubular expression of Serpin E1 was upregulated and positively correlated with tubular senescence and fibrosis in renal tubulointerstitia. Collectively, diabetic insult induces renal tubular degeneration and premature senescence via, at least in part, Serpin E1 signaling.

Catheter-related superior vena cava obstruction: A rare cause of chylothorax in maintenance hemodialysis patients.

With the extensive use of dialysis catheters in patients undergoing hemodialysis, superior vena cava (SVC) syndrome has gradually attracted attention in recent years. Chylothorax caused by SVC syndrome is rarely reported. In this paper, we report a case of chylothorax secondary to superior vena cava obstruction (SVCO) in a maintenance hemodialysis patient after multiple dialysis catheter placements. Relieving the SVCO through intravascular intervention could effectively treat chylothorax. In the past fourteen months, no recurrence of symptoms has been observed.

Cuffed-tunneled hemodialysis catheter survival and complications in pediatric patients: a single-center data analysis in China.

This study aims to evaluate the outcome and complications of cuffed-tunneled catheters in pediatric patients. Between January 2010 and December 2013, 16 pediatric patients with end-stage renal disease (ESRD) were included. 21 cuffed-tunneled hemodialysis catheters were inserted in patients for long-term hemodialysis access. No serious complications were observed in all patients receiving catheter insertion operation, except one with hemopneumothorax. Median survival time was 413.5 days, with rate being 67.5% in the first year, 51.5% in the second year and 43.6% in the third year. Among attempted catheter insertions, 21 (100%) achieved successful vascular access with 13 (61.9%) being remained for the required period and 8 (38.1%) being removed due to death, intractable blood or tunnel infections, catheter thrombosis or malposition. The overall rate of catheter-related infections, thrombosis and malposition was 7.3, 23.4 and 3.4 episodes/1000 catheter days, respectively. Cuffed-tunneled hemodialysis catheters could be effectively used for maintenance of hemodialysis vascular access for pediatric patients with ESRD. Various surveillance measures should be taken to ensure cuffed-tunneled catheters' long-term patency.

Effect of peritoneal dialysis on expression of vascular endothelial growth factor, basic fibroblast growth factor and endostatin of the peritoneum in peritoneal dialysis patients.

AIM: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) in human peritoneum and investigate the relationship between them and peritoneum neoangiogensis in the patients with uraemia and peritoneal dialysis (PD). METHODS: Peritoneal biopsies were obtained from normal subjects (n = 8), uraemic predialysis patients (n = 12) and PD patients (n = 10). The mRNA expression of VEGF, bFGF and ES in peritoneal tissues were measured through real-time polymerase chain reaction. The protein expression of VEGF, bFGF and ES in peritoneal tissues were determined through western blot. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. RESULTS: The mRNA and protein of VEGF, bFGF and ES were expressed in all peritoneal samples. Compared with the normal control group, the mRNA and protein expression of VEGF and bFGF in peritoneal tissues were all significantly upregulated in the uraemic predialysis and PD group (all P < 0.05). Compared with the normal control group, the protein expression of ES were significantly upregulated in the uraemic predialysis and PD group (all (P < 0.05), but the mRNA expression of ES did not have obvious differences in the uraemic predialysis and PD group as compared to the normal control group (P > 0.05). MVD of peritoneal tissue were increased in the uraemic predialysis and PD group compared with the normal group (all P < 0.05). A significant positive correlation was found between VEGF mRNA expression and MVD, bFGF mRNA expression and MVD. CONCLUSION: The mRNA expression of VEGF and bFGF, the protein expression of VEGF, bFGF, and ES and microvessel density (MVD) are increased both in the uraemic predialysis and PD patients. These results show that uraemia circumstances and non-physiological compatibility of peritoneal dialysis solution might increase VEGF, bFGF and ES expression and MVD, which might participate in the increment of the peritoneum neoangiogensis and ultrafiltration failure in PD patients.

Effects of recombinant human endostatin on peritoneal angiogenesis in peritoneal dialysis rats.

AIM: To investigate the effects of recombinant human endostatin (Endostar) on peritoneum angiogenesis in a model of dialysate exposure in rats. METHODS: Forty male Sprague-Dawley rats were randomized to five groups: normal (group 1); uraemia (group 2); 4.25% peritoneal dialysate (PD) uraemic (group 3); uraemia + PD + recombinant human endostatin 10 mg/kg PD (group 4); and uraemia + PD + recombinant human endostatin 40 mg/kg PD (group 5). The uraemic rats model was established by 5/6 nephrectomy. Endostatin was administrated by s.c. injection every other day, over 28 days. After 28 days of PD fluid exposure, immunohistochemistry and reverse transcript polymerase chain reaction were used to detect protein and mRNA expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in each group. Microvessel density (MVD) was measured by immunohistochemistry. RESULTS: Compared with group 1, the mRNA and protein expressions of VEGF and bFGF were significantly upregulated in groups 2 and 3 (P < 0.05). Compared with group 3, the mRNA and protein expressions of VEGF and bFGF were significantly downregulated in groups 4 and 5 (P < 0.05). Compared with group 4, the mRNA and protein expressions of VEGF and bFGF were significantly downregulated in group 5 (P < 0.05). Compared with group 1, MVD was significantly upregulated in groups 2 and 3 (P < 0.05). Compared with group 3, MVD was significantly downregulated in groups 4 and 5 (P < 0.05). CONCLUSION: Endostar can effectively inhibit rat peritoneum neoangiogenesis and the effect was dose-dependent.