RESUMO
Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
Assuntos
Humanos , Inibidores de Calcineurina/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/patologia , Ácido Micofenólico/uso terapêuticoRESUMO
Objective:To evaluate the efficacy and safety of belimumab combined with standard regimen in the treatment of active lupus nephritis (LN).Methods:It was a single-center, pre - and post-control retrospective study. The Data of active LN patients treated with belimumab combined with standard regimen in the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from June 1, 2020 to June 30, 2022 were collected for analyzing the renal response rate and adverse reactions after belimumab treatment.Results:A total of 17 patients were included, including 14 females (82.35%). The age of the first medication was (26.06±2.64) years old, the median time of illness before the use of belimumab was 24.00 (8.50, 48.50) months, and the recurrence times before the use of belimumab was (1.24±1.03) times. All the 17 patients underwent renal biopsy. The main pathological types were type IV in 11 cases (11/17), type Ⅲ+V in 2 cases (2/17), type IV+V in 3 cases (3/17), and type V in 1 case (1/17). The dose of glucocorticoids was (22.95±8.30) mg/d in 1 year before belimumab administration. In 12 patients with LN who completed 24 weeks of belimumab treatment plan, the 24-hour urinary protein showed a downward trend, and there was a statistically significant difference compared with the baseline at 24 week [0.49 (0.15, 2.19) g vs. 2.83 (1.14, 4.11) g, Z=-2.100, P=0.036]. Compared with the baseline, serum albumin at 24 week increased by 29.36%, with statistically significant difference [(34.50±3.34) g/L vs. (26.67±5.75) g/L, t=-3.840, P=0.030]. The systemic lupus erythematosus disease activity index-2K score continued to decline, with statistically significant difference compared with baseline at 24 week (5.00±3.02 vs. 12.00±2.82, t=6.163, P<0.001). The lymphocyte count increased, and the difference was statistically significant compared with the baseline at 24 week [0.72(0.28, 2.39)×10 9/L vs. 0.30(0.19,0.34)×10 9/L, Z=-2.073, P=0.038]. There was a statistically significant difference between the glucocorticoids dosage at 24 week and the average glucocorticoids dosage 1 year before treatment [(11.25±6.35) mg/d vs. (22.60±9.75) mg/d, t=4.225, P=0.003]. After observation of belimumab for (38.13±22.93) weeks, patients had a complete response rate of 64.71% (11/17), a partial response rate of 17.65% (3/17), and an overall response rate of 82.35% (14/17). Relapse occurred in 1 case.No infusion-related reactions occurred in 17 patients. During the treatment, a total of 5 adverse events occurred, including 2 cases of pulmonary infection, 1 case each of sepsis, upper respiratory tract infection, and cytomegalovirus infection, which all improved after treatment and the subsequent treatment was not affected. Conclusion:Belimumab combined with standard regimen can improve the response rate of LN, reduce the recurrence rate, reduce the dosage of glucocorticoids, and control the overall adverse events with good prognosis.
RESUMO
Objective:To assess the bacterial profiles and antimicrobial susceptibility patterns in uropathogens, and help to inform the empiric treatment decisions for urinary tract infection in outpatient settings.Methods:A single institutional retrospective analysis was performed on positive urine cultures from outpatient settings between January 1998 and December 2018. To analyze changes over time, trends analysis were undertaken on bacterial profiles, antimicrobial susceptibility and resistance.Results:A total of 1.172 pathogenic bacteria were isolated after exclusion of duplicate strains originated from the same patient, including 991(84.6%) Gram-negative bacterial strains and 181(15.4%) Gram-positive strains. The most common Gram-negative uropathogens were Escherichia coli (60.8%) and Klebsiella pneumonia (8.1%). Enterococcus faecalis (4.6%) was the predominant Gram-positive strain. The detection rate of Escherichia coli increased significantly, from 50.8% to 63.2% ( χ2=7.978, P=0.046), and no significant difference was observed in the distribution of major uropathogenic bacteria over the 20 years (all P>0.05). The proportion of extended-spectrum β-lactamase (ESBLs) producing strains increased significantly across the 20 years ( P<0.05). The resistance rates of Escherichia coli to amoxicillin and clavulanate potassium, aztreonam, ceftazidime, ciprofloxacin and sulbactam + cefoperazone increased significantly (all P<0.05). All the isolates sustained high susceptibility to tazobactam + piperacillin, amikacin, imipenem and nitrofurantoin (95.0%, 95.7%, 97.9% and 91.1%). Similar to those of Escherichia coli, Klebsiella pneumoniae remained a high and stable sensitivity to tazobactam+piperacillin, amikacin and imipenem during the 20 years (79.1%, 88.0% and 80.3%). However, the proportion of ESBLs producing strains increased significantly ( P<0.05). Among Gram-positive bacteria isolates, the sensitivity rates of Enterococcus faecalis to ampicillin, nitrofurantoin and penicillin G were 100.0%. No vancomycin resistant strain was detected in Gram-positive bacteria. Conclusions:From 1998 to 2018, Escherichia coli and Klebsiella pneumoniae are the most common Gram-negative bacteria uropathogens obtained in outpatient settings. Significant increases of resistance to some antimicrobial agents such as second- and third-generation cephalosporins and fluoroquinolones are observed during the 20 years and high susceptibilities to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin sustain over time. Local treatment strategies of urinary tract infections on outpatient basis should be made according to epidemiology of drug resistance and individual characteristics to control the spread and curb the prevalence of drug resistant.
RESUMO
Objective To explore the clinical characteristics and risk factors of catheterrelated infection in continuous renal replacement therapy (CRRT) patients.Methods The demographic and clinical data of CRRT patients who inserted with double-lumen non-cuffed dialysis catheter at the First Affiliated Hospital of Sun Yat-sen University from January 1,2016 to December 31,2016 were collected.According to the presence or absence of catheter-related infections,they were divided into infected group and uninfected group.Statistics and analysis of the incidence and pathogenic characteristics of catheter-related infections;Comparison of clinical features of infected and uninfected groups;A multivariate Cox proportional hazard model was used to analyze risk factors for catheter-related infections.Results A total of 364 patients with CRRT (437 cases of central venous catheterization) were enrolled in the study.Catheter-related bloodstream infection (CRBSI) and catheterrelated colonization (CRCOL) rates were 3.565 and 2.228 events per 1000 catheter-days.These catheters were associated with higher proportion of inserted in ICU (P=0.007),immunosuppression (P=0.002),receive catecholamine inotropes therapy (P=0.001) and shock (P=0.030).The infection catheters also had shorter indwelling time (P=0.032) and lower level of blood hemoglobin (P=0.017),serum creatinine (P=0.004),blood brain natriuretic peptide (P=0.005) pericatheter use.The most common pathogens were Gram-negative bacteria,especially Acinetobacter baumannii,which caused 37.5％ CRBSI and 20.0％ CRCOL.Multivariate Cox regression model showed female (P=0.029,HR=2.151),diabetes (P=0.016,HR=2.807),receive catecholamine inotropes therapy (P=0.012,HR=2.655),immunosuppression (P=0.037,HR=2.203) were independent risk factors associated with catheterrelated infection.Conclusions The incidence of CRBSI and CRCOL is 3.565 and 2.228 events per 1000 catheter-days CRRT patients in our hospital.The most common pathogen of catherter-related infection is Gram-negative bacteria.Female,diabetes,received catecholamine inotropic drugs,and immunosuppression were independent risk factors associated with catheter-related infection.
RESUMO
Objective To observe the clinical effect of peroutaneous ethanol injection therapy (PEIT) of parathyroid gland guided by color ultrasound on dialysis patients with secondary hyperparathy-roidism. Methods Percutaneons ethanol injection therapy (PELT) was used for seven patients who suf-fered from secondary hyperparathyroidism, and systemic perioperative nursing care and relative health edu-cation were applied. Results All patients had obtained successful operation without any operative sud-denness or associated complications,Patients" serious scratching and bone ache was obviously relieved.Conclusions Treatment with PEIT and effective nursing to patients suffered from secondary hyper-parathyroidism can reduce the complications, and than improve the quality of live for patients.
RESUMO
AIM: To investigate the impact of scavenger receptor class A type Ⅰ/Ⅱ (SR-A Ⅰ/Ⅱ) on the lipid metabolism in SR-A Ⅰ/Ⅱ gene deficient mice. METHODS: A probe of 660 bp fragment of SR-A Ⅰ/Ⅱ cDNA digested with PstⅠ and XhoⅠ from plasmid 122 was used to identify whether SR-A Ⅰ/Ⅱ had been knocked out in the tail DNA of the mutant (SR-/-) and control (SR+/+) mice by the method of Southern-blot analysis. The serum levels of triglycerides(TG), cholesterol(CH), low density lipoprotein(LDL), high density lipoprotein (HDL), apolipoprotein (Apo) A and ApoB of the mice fed with normal food and higher lipid food respectively were tested by biochemical method. RESULTS: The serum levels of LDL and body weights of group with SR-A Ⅰ/Ⅱ gene knocked out were higher than that of control group ( P
RESUMO
AIM: To investigate the expression and functional role of p38MAPK in the kidney after unilateral ureteral obstruction in rats. METHODS: Unilateral ureteral obstruction (UUO) models were induced by ligating the left ureter. Rats were sacrificed at 1 h, 3 h, 6 h, 12 h, 1, 3, 5, 7, 14, 21, and 28 days after UUO was initiated. p38MAPK activity was assayed by immunohistochemical staining and specific substrate phosphorylation with immunoprecipitation and Western blotting. TGF? mRNA and protein expression were analyzed with in situ hybridization and immunohistochemical stainning. RESULTS: A basic p38MAPK activity was detectable in the normal kidney(0.22?0.06). p38MAPK pathway was rapidly activated at 1 hour(0.45?0.14 vs control, P
