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Background: To observe the short-term outcome of plasma adsorption PA therapy in amyotrophic lateral sclerosis (ALS). Methods: 28 cases of ALS patients were recruited in this study, of which 20 were male and 8 were female with a mean age of 53.21±9.07 years and the average course of 33±23.35 months. The clinical manifestations were limb weakness (N=27), muscular atrophy (N=27), muscular tremor (N=5), dysphagia (N=12) and dysarthria (N=12). The clinical data of the patients recruited were graded by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRSR) : 40 (N=5). All patients received PA therapy once a week for three successive times after examining the conditions of blood coagulation and virus infection. PA therapy was supplemented with neurotrophic therapy meanwhile. All patients' clinical manifestations and scores of ALSFRSR before treatment and one week after treatment were evaluated and compared. The levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), serum creatine kinase (CK) and lactate dehydrogenase (LDH) before and after treatment were compared. Results: After PA therapy, 14 patients have improved obviously in muscle strength, 4 patients in hypermyotonia partially, 3 patients in muscular tremor, 5 patients in dysarthria, 3 patients in salivation to some extent and 2 patients in swallowing function. The score of ALSFRSR after PA treatment (31.89±10.36) was remarkably higher than that before PA treatment (30.68±10.52) (P

BACKGROUND Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it. METHODS This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association. RESULTS A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; P  = 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event. CONCLUSIONS Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings. CLINICAL TRIALS REGISTRATION There is no clinical trial registration for this retrospective study. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain. Objectives: This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF. Methods: HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. Results: The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05). Conclusions: HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD. [ABSTRACT FROM AUTHOR]

Abstract Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy.

Objective: To explore the value of baseline serum alkaline phosphatase (ALP) for predicting 2-year fracture in patients with chronic kidney disease (CKD) on maintenance dialysis., Methods: A total of 139 patients with CKD undergoing maintenance dialysis in our hospital were enrolled in this study. According to the median serum ALP level, the patients were divided into high ALP and low ALP groups. The demographic and clinical data of the patients including dialysis duration, serum calcium level, serum phosphorus level, and serum intact parathyroid hormone level were recorded, and their bone mineral density of the femur and the lumbar spine was measured using dual energy X-ray absorptiometry. The patients were followed up for 2 years and fracture events were recorded. The risk factors of fracture were analyzed using logistic regression analysis, and their predictive value for fracture was analyzed using receiver-operating characteristic (ROC) curve., Results: The mean baseline serum ALP level was 132.55±167.68 U/L in these patients, significantly higher than that in the normal population ( t =2.816, P =0.006). Baseline serum ALP level was negatively correlated with the bone mineral density of the lumbar spine ( r =-0.203, P =0.006) and the femur ( r =-0.196, P =0.021). Fractures occurred in 21 (15.1%) of the patients during the 2-year follow-up, and the fracture rate was significantly higher in patients with high ALP levels. Logistic regression analysis identified serum ALP level as an independent risk factor of fracture (OR: 1.010, P =0.001, 95%CI: 1.004-1.016). The areas under the ROC curve were 0.900 and 0.768 for serum ALP level and intact parathyroid hormone level in predicting 2-year fractures, respectively., Conclusions: Serum ALP may serve as a good indicator for predicting 2-year fractures in patients with CKD on maintenance dialysis.

Objective: Transforming growth factor-beta (TGF-beta) has been shown to play a role in peritoneal complications due to long-term peritoneal dialysis (PD). In this study, we examined the effects of the TGF-beta signaling pathway on peritoneal inflammation associated with PD in rats by over-expressing Smad7, an inhibitor of TGF-beta/Smad signaling., Methods: Peritoneal inflammation was induced in male Sprague-Dawley rats by intraperitoneal injections of 4.25% glucose dialysate (100 mg/kg body weight) daily for 4 weeks, with the addition of lipopolysaccharides (0.6 mg/kg body weight) on days 8, 10, 12, 22, 24, and 26. Peritoneal Smad7 gene transfer was achieved using an ultrasound microbubble mediated, doxycycline regulated, Smad7-expressing plasmid on day 0 and day 14 after initiation of PD. An empty vector was used as control. All rats were sacrificed after 4 weeks of PD. Peritoneal inflammatory response, including infiltration of total leukocytes (OX-1 positive) and macrophages (ED-1 positive) and expression of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), was examined by immunofluorescence and RT-PCR., Results: After PD, peritoneal inflammation developed in control animals, as demonstrated by an increase in the number of OX-1-positive and ED-1-positive cells and upregulation of IL-1beta and TNF-alpha mRNA and protein expression. In contrast, in animals treated with Smad7 gene transfer, IL-1beta and TNF-alpha expression and OX-1-positive and ED-1-positive cell infiltration were significantly inhibited. Furthermore, prevention of peritoneal inflammation by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad2/3, a downstream of the TGF-beta signaling pathway, as well as TGF-beta1 expression., Conclusion: Overexpression of Smad7 suppresses peritoneal inflammation induced by high glucose and lipopolysaccharides. The ability of Smad7 gene transfer to inhibit peritoneal inflammation indicates that targeting TGF-beta/Smad signaling may represent a new therapeutic strategy for the treatment of peritoneal complications associated with PD.