Impact of Dexmedetomidine On Secondary Hyperparathyroidism Recurrence In Uremic Patients Who Received Parathyroidectomy With Auto-Transplantation: A Retrospective Propensity-Matched Study

Background: Recurrence of secondary hyperparathyroidism (SHPT) remains a big challenge in uremic patients who underwent total parathyroidectomy with auto-transplantation (tPTX-AT). However, the relationship between perioperative intervention and recurrence of SHPT remains unclear. Dexmedetomidine has been used safely and effectively in uremic patients’ anesthesia. The aim of the study was to explore the effect of dexmedetomidine on the recurrence of SHPT and speculate the possible mechanism of action.Methods: Records of patients who underwent tPTX-AT between 2017 and 2018 were retrospectively analyzed. The study consisted of patients who received dexmedetomidine intra-operatively and the controls were patients who did not receive dexmedetomidine. The primary endpoint was the difference in the recurrence of SHPT one year after surgery between the two groups. The secondary endpoint was health-related quality of life scores. Analysis included propensity score matching and multivariable logistic regression. Results: Of 354 patients, 133 patients received dexmedetomidine intraoperatively, and the total recurrence rate of SHPT was 10.2%. After propensity score matching, patients who received dexmedetomidine had a 3.80-fold decreased risk of SHPT recurrence (odds ratio, 0.263; 95% confidence interval, 0.081 to 0.854; P=0.026) and exhibited a better quality of life in terms of physical functioning and general health, and less emotional role limitations compared with those in control group.Conclusion: In uremic patients who received tPTX-AT, there was an association between dexmedetomidine use and decreased risk of SHPT recurrence. Further studies are needed to accurately assess the effects and mechanism of action of dexmedetomidine on the prognosis of this population.

Non-invasive Myocardial Work Index Contributes to Early Identification of Impaired Left Ventricular Myocardial Function in Uremic Patients With Preserved Left Ventricular Ejection Fraction

BackgroundCardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients.MethodsTwenty-six uremic patients and twenty-seven age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients.ResultsCompared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P< 0.05). Area under the curve (AUC) for GWE by the ROC analysis was 0.966. The best threshold, sensitivity and specificity values of GWE to detect abnormality of LV systolic function in uremic patients were 92.5%, 0.89 and 0.96 respectively. ConclusionsNIMWI may be applied to assess the global MW of uremic patients. The presence of reduced GWE can help identify impaired left ventricular myocardial function in uremic patients with preserved LV ejection fraction with a high sensitivity and specificity.

The Influence of OAT1 Density and Functionality on Indoxyl Sulfate Transport in the Human Proximal Tubule: An Integrated Computational and In Vitro Study

Research has shown that traditional dialysis is an insufficient long-term therapy for patients suffering from end-stage kidney disease due to the high retention of uremic toxins in the blood as a result of the absence of the active transport functionality of the proximal tubule (PT). The PT’s function is defined by the epithelial membrane transporters, which have an integral role in toxin clearance. However, the intricate PT transporter–toxin interactions are not fully explored, and it is challenging to decouple their effects in toxin removal in vitro. Computational models are necessary to unravel and quantify the toxin–transporter interactions and develop an alternative therapy to dialysis. This includes the bioartificial kidney, where the hollow dialysis fibers are covered with kidney epithelial cells. In this integrated experimental–computational study, we developed a PT computational model that focuses on indoxyl sulfate (IS) transport by organic anionic transporter 1 (OAT1), capturing the transporter density in detail along the basolateral cell membrane as well as the activity of the transporter and the inward boundary flux. The unknown parameter values of the OAT1 density , IS uptake (, and dissociation ( were fitted and validated with experimental LC-MS/MS time-series data of the IS concentration. The computational model was expanded to incorporate albumin conformational changes present in uremic patients. The results suggest that IS removal in the physiological model was influenced mainly by transporter density and IS dissociation rate from OAT1 and not by the initial albumin concentration. While in uremic conditions considering albumin conformational changes, the rate-limiting factors were the transporter density and IS uptake rate, which were followed closely by the albumin-binding rate and IS dissociation rate. In summary, the results of this study provide an exciting avenue to help understand the toxin–transporter complexities in the PT and make better-informed decisions on bioartificial kidney designs and the underlining transporter-related issues in uremic patients.

Comparison of Outcomes between Percutaneous and Surgical Placement of Peritoneal Dialysis Catheters in Uremic Patients: A Meta-Analysis

<b><i>Background:</i></b> The optimal technique for inserting peritoneal dialysis catheters in uremic patients remains debated. This meta-analysis aimed to summarize the current evidence evaluating the efficacy and safety of percutaneous insertion methods compared to surgical methods. <b><i>Method:</i></b> A literature search was performed in the PubMed, EMBASE, Cochrane, and Web of Science databases. The primary outcome was defined as catheter survival. The secondary outcomes were mechanical and infectious complications related to catheter insertion. <b><i>Results:</i></b> Twenty studies were finally identified, including 2 randomized controlled trials. The pooled results of catheter survival, overall mechanical complications, and infectious complications were not significant (odds ratio [OR] = 1.10, 95% confidence interval (CI) = 0.76–1.57, <i>p</i> = 0.62; OR = 0.73, 95% CI = 0.48–1.11, <i>p</i> = 0.14; and OR = 0.64, 95% CI = 0.37–1.09, <i>p</i> = 0.14, respectively). Comparison stratified by the blind percutaneous method versus open surgery indicated a lower overall number of mechanical complications (OR = 0.54, 95% CI = 0.31–0.93, <i>I</i>² = 72%) and malposition rate (OR = 0.56, 95% CI = 0.34–0.90, <i>I</i>² = 0%). The leakage rate was higher in the blind percutaneous group than in the open surgery group (OR = 2.55, 95% CI = 1.72–3.79, <i>I</i>² = 0%); the guided percutaneous method achieved a similar leakage risk to the surgical methods. <b><i>Conclusions:</i></b> The blind percutaneous method performed better with fewer overall mechanical complications and less malposition than open surgery. The leakage risk was higher in the blind percutaneous group, while the guided percutaneous placement group showed similar outcomes to the surgical method groups. Percutaneous methods also had a lower infection risk, which needs further evidence to be confirmed.

Effect of Nutritional Nursing on the Quality of Life, Nutritional Status, and Complications in Elderly Uremic Patients Receiving Peritoneal Dialysis

Objective: The aim of this study is to explore the role of nutritional nursing in the quality of life, nutritional status, and complications in elderly uremic patients receiving peritoneal dialysis (PD). Methods: We enrolled 205 uremic patients who were treated with PD in our hospital from March 2018 to April 2019 as the research subjects. Then we grouped them according to different nursing methods: 116 cases receiving nutritional nursing were assigned to the research group (RG) while the other 89 cases receiving routine nursing to the control group (CG). Clinical biochemical markers were detected by the biochemistry analyzer, the nutritional status determined by the Modified Quantitative Subjective Global Assessment (MQSGA), the anxiety and depression intensity assessed by Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS), the sleep quality assessed by the Pittsburgh Sleep Quality Index(PSQI), the nursing satisfaction level assessed by the hospital’s self-made nursing satisfaction questionnaire, and the quality of life evaluated by the Quality of Life Questionnaire (QLQ-C30 ). The complication rate in patients was monitored. Results: The improvement of clinical biochemical markers after nursing was better in RG than in CG. The decrease in the MQSGA score, SAS score, SDS score, and PSQI score after nursing was sharper in RG than in CG. Compared with CG, RG had a remarkably lower complication rate, a notably higher nursing satisfaction level, and a remarkably better quality of life. Conclusion: Nursing intervention for elderly uremic patients receiving PD can enhance the quality of life of patients, improve the nutritional status, promote the recovery from the disease, and reduce the complication rate.

MO900ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING PROTEIN (TXNIP) RESULTS IN REDUCED TRX ACTIVITY AND INCREASED OXIDATIVE DNA-DAMAGE IN PERITONEAL DIALYSIS PATIENTS*

Background and Aims Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as a RRT is limited due to adverse effects of high glucose-based PD solutions to the structure and function of the peritoneal membrane. PD patients show excessive oxidative stress compared to healthy controls. However, there are only scare information on pathophysiological mechanisms leading to oxidative DNA-damage in PD patients. Therefore, the aim of this study was to elucidate the mechanism leading to excessive oxidative stress in human samples of the peritoneal membrane. Method Human peritoneal biopsies of healthy controls, PD patients and patients with EPS were collected. Protein expression of TXNIP was analysed by ELISA using plasma samples and by immunohistochemistry of peritoneal biopsies using a Histo-Score. Protein expression of TRX was examined by immunohistochemistry. To measure TRX activity a kit based on the reduction of insulin by reduced TRX was used. The resulting oxidative DNA-damage was investigated by immunohistochemistry using a Histo-Score or by ELISA using plasma samples of patients. Results Biopsies from the peritoneum of 8 healthy controls, 11 uremic patients, 22 patients on PD &lt; 12 months or 29 patients on PD &gt; 12 months and of 13 patients with EPS were collected. The age of the uremic patients was higher (median 65.0 years, IQR: 49.0-75.0) than in the other subgroups (PD &lt; 12 months: median 62.0 years, IQR: 52.25-68.25, PD &gt; 12 months: median 60.0 years, IQR: 39.5-70.5 and EPS: median 51.00 years, IQR: 40.0-57.5). In general, there were more female participants in the control-group (75 %) compared to all other groups (uremic group: 27%, PD &lt; 12 months: 18 %, PD &gt;12 months: 41% and EPS group 33 %). Time on PD was longer in EPS patients (median 72.0 months) than in PD patients (PD &lt;12 months: median 10.0 months and PD &gt; 12 months: 39.0 months). The ELISA study of plasma samples showed that TXNIP is upregulated in all groups compared to healthy controls. Immunohistochemically studies of peritoneal biopsies showed also an upregulation of TXNIP upon exposure to high glucose-based dialysis fluids (PD and EPS group). Interestingly, a glucose-related change in protein expression of its interacting partner and cellular anti-oxidant TRX was only observed in EPS samples. TRX activity in uremic patients was almost unchanged compared to healthy controls except for one patient. However, enhanced TXNIP expression correlated with a reduced activity of TRX in samples of PD as well as EPS patients. Reduced TRX activity resulted in an increase of produced ROS. Therefore, the effect on the generation of oxidative damage was analysed by ELISA of plasma samples and by immunohistochemistry on peritoneal sections. Both analysis showed an increase in the oxidative DNA-damage marker 8-Hydroxydesoxyguanosin (8-OHdG) in all PD samples and samples of EPS patients compared to the control group. Conclusion Here, we show that high glucose-based peritoneal dialysis solutions lead to an upregulation of TXNIP expression in human peritoneal samples. This increase in TXNIP expression reduces the activity of its interacting partner an antioxidant TRX leading to an increase in ROS production and enhanced levels of DNA-damage. In this study, we elucidate for the first time a novel mechanism showing that glucose-dependent upregulation of TXNIP induces a perturbation of the intracellular redox equilibrium leading to alterations of the peritoneal membrane. Therefore, manipulation of TXNIP expression may be a promising therapeutic target to improve peritoneal membrane function.

Local NF-κB activation promotes parathyroid hormone synthesis and secretion in uremic patients

Secondary hyperparathyroidism (SHPT) in uremic patients characterizes by parathyroid gland (PTG) hyperplasia and parathyroid hormone (PTH) elevation. Previously, we demonstrated that NF-κB activation contributed to parathyroid cell proliferation in chronic kidney disease (CKD) rats. Although vitamin D inhibits inflammation and ameliorates SHPT, the contribution of vitamin D deficiency to SHPT via local NF-κB activation remains to be clarified. PTGs collected from 10 uremic patients with advanced SHPT were used to test the expressions of vitamin D receptor (VDR), NF-κB, and proliferating cell nuclear antigen (PCNA). Freshly excised PTG tissues were incubated for 24 h in vitro with VDR activator (VDRA) calcitriol or NF-κB inhibitor Pyrrolidine Thiocarbamate (PDTC). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate the regulation of PTH transcription by NF-κB. We found higher levels of activated NF-κB and lower expression of VDR in nodular hyperplastic PTGs than in diffuse hyperplasia. In cultured PTG tissues, treatment with VDRA or PDTC inhibited NF-κB activation and PCNA expression, and downregulated preproPTH mRNA and intact PTH levels. ChIP assays demonstrated the presence of NF-κB binding sites in PTH promoter. Furthermore, in luciferase reporter assays, addition of exogenous p65 significantly increased PTH-luciferase activity by 2.4-fold (p&lt;0.01), while mutation of NF-κB binding site at position –908 of the PTH promoter suppressed p65-induced PTH reporter activity (p&lt;0.01). In summary, local NF-κB activation contributes to SHPT and mediates the transcriptional activation of PTH directly in uremic patients. Vitamin D deficiency may be involved in SHPT via the activation of NF-κB pathway.