Kidney transplantation (KT) is one primary treatment of end-stage renal disease (ESRD). As reported by different centers, 10-year survival rate of transplanted kidneys fluctuates from 75% to 80%. Capable of reducing all-cause mortality in renal failure, KT can significantly improve survival rate and quality-of-life of ESRD patients. The risk of post-transplant rejection is much higher in pre-sensitised recipients than in non-sensitised ones due to the pre-existing anti-human leukocyte antigen antibodies. However, with a rapid development of various desensitisation techniques, transplantation rate and postoperative human/kidney survival rate of recipients have been greatly enhanced. And presensitisation is no longer a contraindication to KT. This review focused upon the latest advances in desensitisation therapeutic agents for pre-sensitised KT.

Objective:To explore the clinical efficacy of immunoadsorption in highly sensitized kidney transplant (KT) candidates.Methods:From September 2019 to April 2023, the relevant clinical data were retrospectively reviewed for 26 highly sensitized KT recipients. Protein A immunoadsorption desensitization therapy was offered after KT. The effect of immunosorbent on reducing anti-human leukocyte antigen (HLA) antibodies was summarized. And operative success rate and postoperative complication incidence were calculated.Results:The mean number of treatment session was (10.76±5.53). The highest level of HLA-Ⅰ antibody mean fluorescence intensity (MFI) dropped from (17 921±4 442) to (7 333±6 434) with a decline of 59% and HLA-Ⅱ antibody MFI decreased from (21 135±5 245) to (10 989±7 627) with a decline of 48%. The differences were statistically significant (both P<0.001). All kidneys were harvested from cadavers. The complications were acute antibody mediated rejection (7 cases), perioperative pulmonary infection (3 cases) and myelosuppression (2 cases). The average follow-up period was (30.8±12.6) month. The graft survival rate was 88.5% (23/26) and the recipient survival rate 100% (26/26) . Conclusions:Immunoadsorption therapy can effectively reduce HLA antibody in highly sensitized KT candidates, thereby increasing the probability of successful KT. In terms of safety, immunosorbent therapy may boost the potential risks of infection and myelosuppression. It requires heightened attention.

Chronic kidney disease has been a global public health problem with a heavy disease burden.As a kidney replacement therapy, kidney transplantation(KT)has a higher long-term survival rate and quality-of-life as compared with dialysis.Antibody-mediated rejection(AMR)is a major complication after KT.Currently its core treatments are steroid hormones, plasma exchange and immunoglobulin.However, the effectiveness of new therapeutic agents such as anti-CD20 antibody and bortezomib has remained controversial.Despite these combination treatments, AMR is still a predominant cause of graft loss and it is imperative to seek novel effective treatments.Interleukin-6(IL-6)is a vital cytokine involved in the regulation of inflammation and the development, maturation and activation of T/B cells.Specifically targeting IL-6, ptolizumab and crazizumab are currently widely applied for managing AMR and blunting highly sensitized KT recipients.This review summarized the clinical applications of IL-6 for AMR.

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

In the COVID-19 epidemic prevention and control work, not only the safety management of in-hospital organ transplantation is facing severe challenges, but also a large number of patients at home after transplantation are in immunosuppressive state, and professional protection management is urgently needed. Since the outbreak of the epidemic, Shulan(Hangzhou)hospital fully identified the risks of transplant patients, established a special team, and formulated and implemented the control management plan for organ transplant patients based on the crisis leadership model. The control management plan has achieved staged results.From January 15 to March 2, 2020, 29 liver transplants and 31 kidney transplants were performed in our hospital. The remote health education of 1 002 patients after liver and kidney transplantation was completed. The goal of " zero infection" was achieved, and the protection management quality indicators were ideal.

OBJECTIVE: To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats. METHODS: Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg·d adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and <0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out. RESULTS: Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all <0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all <0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism. CONCLUSIONS Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism.
Animals ; Biomarkers ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; urine ; Male ; Metabolome ; drug effects ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

OBJECTIVETo investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD).

METHODSThe clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality.

RESULTSCompared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival.

CONCLUSIONPatients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.

Humans ; Kidney Failure, Chronic ; mortality ; therapy ; Peritoneal Dialysis ; Proportional Hazards Models ; Renal Dialysis ; Retrospective Studies ; Risk Factors ; Survival Rate

Hookworm infections as well as other intestinal nematodiases are endemic in China. In this case, a 70-year-old male showed symptoms of chest tightness, shortness of breath, and both lower extremities edema. The diagnostic result was chronic renal insufficiency, chronic kidney disease (5th stage), and renal anemia at first. Then, he received treatment with traditional drugs. However, this treatment did not help to alleviate the symptoms of the patient significantly. The results of gastroendoscopy showed hookworms in the duodenum, also confirmed by pathology examination. Anemia was markedly ameliorated after eliminating the parasites. The results mentioned above suggested that ancylostomiasis was the leading causes of anemia in this patient, and the etiology of anemia in uremic patients should be systematically considered. Especially when anemia could not be cured by regular treatments, rare diseases should be investigated.
Aged ; Ancylostomatoidea* ; Ancylostomiasis ; Anemia* ; China* ; Duodenum ; Dyspnea ; Edema ; Hookworm Infections ; Humans ; Lower Extremity ; Male ; Parasites ; Pathology ; Peritoneal Dialysis* ; Rare Diseases ; Renal Insufficiency, Chronic ; Thorax

Objective:To explore the effect of lipoic acid on oxidative stress,inflammation and nutritional status in peritoneal dialysis patients.Methods:94 peritoneal dialysis patients were randomly divided into the observe group(n=47) the control group(n=47).They all accepted the conventional treatment,but the patients in the observed group were given the treatment of lipoic acid capsules(0.2 g tid) for 12 weeks.Superoxide dismutase(SOD),malondialdehyde(MDA),serum advanced oxidation protein products ( AOPPs ) were used to reflect the level of oxidative stress, high sensitive CRP, IL-6 and TNF-αwere used to reflect the micro inflammatory state, modified quantitative subjective global assessment ( MQSGA ) , mid-arm circumference, mid-arm muscle circumference,triceps skinfold thickness ( TSF ) , body mass index ( BMI ) , and serum albumin were used to reflect the nutritional status.The difference of oxidative stress, micro inflammatory state and nutritional status were compared between the two groups.Results:①In the observation group,the concentrations of AOPPs and MDA after treatment were significantly lower than that before treatment,and the concentration of SOD after treatment was significantly higher than that before treatment ( P<0.05 );after treatment,the concentrations of AOPPs and MDA in the observe group were significantly lower than that in the control group(P<0.05), and the concentration of SOD in the observe group was significantly higher than that in the control group ( P<0.05 ) .②In the observation group,the concentrations of high sensitive CRP,IL-6 and TNF-αafter treatment were significantly lower than that before treatment(P<0.05);after treatment,the concentrations of high sensitive CRP,IL-6 and TNF-αin the observe group were significantly lower than that in the control group ( P<0.05 ) .③In the observation group, the TSF, mid-arm circumference, mid-arm muscle circumference,BMI and albumin after treatment were significantly higher than that before treatment(P<0.05),and the MQSGA after treatment was significantly lower than that before treatment ( P<0.05 );after treatment, the MQSGA in the observe group was significantly lower than that in the control group(P<0.05),and serum albumin in the observe group was significantly higher than that in the control group(P<0.05).Conclusion:Lipoic acid could improve oxidative stress in peritoneal dialysis patients,so as to improve the micro inflammatory state and nutritional status.