The antioxidative effects of empagliflozin on high glucose­induced epithelial-mesenchymal transition in peritoneal mesothelial cells via the Nrf2/HO-1 signaling.

High glucose (HG)-induced epithelial-mesenchymal transition (EMT) and oxidative stress play an important role in peritoneal fibrosis, which could be regulated by the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. This study aimed to investigate whether empagliflozin could inhibit HG-induced EMT and oxidative stress via activating the Nrf2/HO-1 signaling pathway. We used HG-based peritoneal dialysis (PD) solution in rats and HG in human peritoneal mesothelial cells (HPMCs) to induce EMT in vivo and in vitro respectively. The peritoneal structure and function were evaluated by hematoxylin and eosin, Masson's trichrome staining, and the peritoneal equilibrium test. Oxidative stress was measured by assay kits. EMT was analyzed using immunohistochemistry and western blot. The PD rats showed decreased ultrafiltration capacity and increased levels of oxidative stress. Histopathological analysis revealed markedly peritoneal thickening, excessive collagen deposition, increased expression of α-SMA, Collagen-I, and Fibronectin, and decreased expression of E­cadherin. Empagliflozin significantly ameliorated the aforementioned changes. The protein expression levels of nuclear Nrf2 (N-Nrf2) and HO-1 increased in PD rats, which were further promoted by treatment with empagliflozin. In in vitro experiments, the EMT of HPMCs was induced with 60 mM glucose for 24 h and inhibited by empagliflozin. Empagliflozin suppressed oxidative stress and promoted the protein expression of N-Nrf2 and HO-1 in HG­stimulated HPMCs, which was reversed by the Nrf2 inhibitor. In conclusion, empagliflozin exerted a protective effect against HG-induced EMT and suppressed oxidative stress in PMCs by activating the Nrf2/HO-1 signaling pathway.

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

Background: L-carnitine is an endogenous vitamin-like amino acid derivate which plays an essential role in energy metabolism and can be easily lost via dialysis. Deficiency of L-carnitine has great effects on many aspects of bodily functions. To determine the deficiency degree and adjust the supplementation dose, a rapid, sensitive, and specific method for the detection of endogenous L-carnitine in the plasma of dialysis patients using ultra-high performance liquid chromatography-Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-HRMS) was developed and validated. Methods: The plasma samples were processed by protein precipitation and centrifugation before analysis using UHPLC-Orbitrap-HRMS. Sample separation was achieved with a hydrophilic interaction liquid chromatography (HILIC) column, using an isocratic elution with a runtime of 5 min. The separated analytes were detected by positive ionization mode in full scan mode and targeted-single ion monitoring (t-SIM) mode. Mildronate was used as the internal standard (IS). Results: All the plasma could be detected in the range of 6.169 to 197.394 µM, with adequate accuracy, precision, and recovery. The method was validated in fortified validation with relative standard deviations (RSD) 5.15-8.74%. This method was applied to the analysis of 105 dialysis patients and 39 healthy participants, the results revealed that peritoneal dialysis patients without L-carnitine supplementation should pay more attention to L-carnitine monitoring, meanwhile, all the hemodialysis patients were advised to be routinely given a full dose of L-carnitine, no matter whether they had taken L-carnitine or not. Conclusions: This study developed a simple and rapid UHPLC-Orbitrap-HRMS method for detection of endogenous L-carnitine in dialysis patients, which could be useful to promote rational drug use.

Evaluation of laboratory parameters and symptoms after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

Objectives: The aim of the study was to evaluate the laboratory parameters and symptoms after parathyroidectomy (PTX) in dialysis patients with secondary hyperparathyroidism (SHPT), and to briefly analyze the different therapeutic effects of the three surgical methods. Methods: A total of 182 dialysis patients who underwent PTX between February 2012 and January 2018 at the Second Affiliated Hospital of Soochow University were included in this study and followed for 12 months. Laboratory parameters such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were measured before and after operation. According to the follow-up time and type of operation, we calculated the percentage of laboratory indicators reaching the recommended range of the KDIGO guidelines after surgery. We also analyzed the improvement of bone pain and pruritus, as well as surgical complications. Results: After the operation, the levels of iPTH, Ca, and P decreased significantly at each time point. ALP increased at the first postoperative week and gradually decreased to normal range after 3 months. Symptoms, such as bone pain and pruritus, were significantly relieved. According to the follow-up time and three surgical methods (subtotal parathyroidectomy, total parathyroidectomy, total parathyroidectomy plus autologous transplantation), we found that the ratio of each laboratory parameter reaching the recommended range of KDIGO guidelines was significantly different. Conclusion: PTX is a safe and effective therapy for treating SHPT that is refractory to medical therapies and accompanied by related signs and symptoms in dialysis patients. All three operative techniques were effective in controlling SHPT.

Efficacy of APD in perioperative period of non-abdominal operation for peritoneal dialysis patients.

Objectives: Whether automated peritoneal dialysis (APD) is a feasible strategy in perioperative period of uremic patients undergoing nonabdominal surgery remains unclear. This study was conducted to research the perioperative management and the best choice of dialysis modalities for peritoneal dialysis patients. Materials and methods: A retrospective analysis was made on the clinical data of 58 ESRD patients who had received peritoneal dialysis for more than three months were treated with APD during perioperative period from July 2015 to March 2018 in the Second Affiliated Hospital of Soochow University. The differences of clinical parameters, such as urine volume, ultrafiltration volume, hemoglobin, renal function and electrolytes were collected and analyzed before and after APD. Results: The vital signs of 58 patients were stable after APD treatment, and there were no significant differences in 24-hour urine volume, hemoglobin and electrolytes (calcium, phosphorus, potassium, sodium) before and after surgery (P>0.05). Compared with those before treatment, the amount of ultrafiltration increased significantly (P<0.05), creatinine, urea nitrogen and parathyroid hormone decreased significantly (P<0.05), while albumin decreased (P<0.05). Conclusion: Application of APD for peritoneal dialysis patients undergoing nonabdominal surgery during the perioperative period is safe and effective.

Impact of early-onset peritonitis on mortality and technique survival in peritoneal dialysis patients.

BACKGROUND: Early onset peritonitis (EOP) is not uncommon in peritoneal dialysis patients. We aimed to compare the prognosis of EOP and non-EOP peritoneal dialysis patients. METHODS: This study included subjects that underwent PD from January 1, 2004 to July 31, 2013. Patient characteristics were collected. EOP was defined as peritonitis occurring within 6 months after initiation of PD. Patient and technique survival were compared between EOP and non-EOP patients using Cox regression analyses. RESULTS: In total, 189 subjects were included in this study. Patients were divided into EOP (n = 55) and non-EOP groups (n = 134). There was no significant difference in the causative organisms of peritonitis between the two groups. After adjusting for age, diabetes status, serum albumin level and residual renal function, the multivariable Cox regression model revealed that EOP was an independent risk factor for patient mortality (HR 2.03, RI 1.09-3.80, p = 0.026), technique failure (HR 1.69, RI 1.12-2.87, p = 0.015) and total survival (HR 1.73, RI 1.12-2.68, p = 0.013). CONCLUSIONS: EOP was identified as an independent risk factor for mortality and technique failure in peritoneal dialysis patients.

Risk Factors for New-Onset Cardiac Valve Calcification in Patients on Maintenance Peritoneal Dialysis.

OBJECTIVE: Patients with end-stage renal disease are susceptible to cardiac valve calcification (CVC) due to mineral metabolism disorders and other factors. The purpose of this study was to investigate the risk factors for new-onset CVC in patients on maintenance peritoneal dialysis (PD). METHODS: This study included patients who underwent PD catheter insertion from January 2006 to June 2013 in our Peritoneal Dialysis Center. Clinical data were collected on CVC status during echocardiography evaluations (twice) at an interval of >6 months. The data collected included intact parathyroid hormone, C-reactive protein (CRP), serum phosphorus (P), serum calcium (Ca), albumin (Alb), prealbumin and the use of five types of antihypertensive drugs, statins, active vitamin D3 and Ca tablets. RESULTS: In total, 194 patients - 105 (54.1%) men, average age 60.5 ± 13.0 years - were included. CVC was present in 50 (25.8%) patients during PD catheter placement. After an average PD duration of 20.9 ± 10.4 months, CVC was detected in 97 patients (50.0%). New-onset CVC was found in 62 patients (32.0%). Multivariate logistic regression analysis revealed that only serum P levels (p = 0.01, OR = 2.569), Alb levels (p = 0.04, OR = 0.935), dialysis duration (p = 0.03, OR = 1.039) and CRP levels (p = 0.02, OR = 1.031) were associated with CVC. CONCLUSION: Serum P, Alb and CRP levels as well as dialysis duration are independent risk factors for CVC.

Early peritonitis is an independent risk factor for mortality in elderly peritoneal dialysis patients.

BACKGROUND/AIMS: The impact of early peritonitis on the outcome of elderly peritoneal dialysis (PD) patients has not been studied. We aimed to research the influence of early peritonitis on patient outcomes in elderly PD patients. METHODS: This study involved elderly PD patients (age ≥65) who underwent PD between Jan 1, 2004 and Jul 31, 2013. Patient characteristics were collected in our database. Early peritonitis was defined as peritonitis within 6 months after the initiation of PD. Patient survival and technique were compared among the non-peritonitis, early peritonitis and late peritonitis groups using Cox regression analysis. RESULTS: There were 155 subjects involved in this study. The patients were divided among a non-peritonitis group (n=78), early peritonitis group (n=32) and late peritonitis group (n=45). The organisms causing first peritonitis in the two groups did not differ significantly. After adjustment for age, diabetes, serum albumin and residual renal function, multivariable Cox regression model revealed that compared with the early peritonitis group, both the non-peritonitis group (HR 0.57, RI 0.32-0.99, p=0.046) and the late peritonitis group (HR 0.37, RI 0.16-0.75, p=0.004) exhibited a lower patient mortality rate. CONCLUSIONS: Early peritonitis is an independent risk factor for mortality in elderly peritoneal dialysis patients.

Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model.

Accumulating evidence has demonstrated that hydrogen sulfide (H2S) plays critical roles in the pathogenesis of chronic kidney diseases. This study was designed to investigate whether H2S has protective effects against diabetic nephropathy. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administrated with H2S donor NaHS for 12 weeks. Rat glomerular mesangial cells were pretreated with NaHS or MAPK inhibitors (U0126, SP600125, and SB203580) prior to high glucose exposure, and cell proliferation was determined. Our findings suggest that H2S can improve renal function and attenuate glomerular basement membrane thickening, mesangial matrix deposition, and renal interstitial fibrosis in diabetic rats. H2S was found to reduce high glucose-induced oxidative stress by activating the Nrf2 antioxidant pathway and to exert anti-inflammatory effects by inhibiting NF-κB signaling. In addition, H2S reduced high glucose-induced mesangial cell proliferation by blockade of MAPK signaling pathways. Moreover, H2S was also found to inhibit the renin-angiotensin system in diabetic kidney. In conclusion, our study demonstrates that H2S alleviates the development of diabetic nephropathy by attenuating oxidative stress and inflammation, reducing mesangial cell proliferation, and inhibiting renin-angiotensin system activity.