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1.
Int J Artif Organs ; : 3913988241259963, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869042

RESUMO

In this study, we investigated the effectiveness of regional citrate anticoagulation continuous renal replacement therapy (RCA-CRRT) in reducing blood calcium levels in three patients with hypercalcemia crisis caused by different etiologies. The sodium citrate chelation of calcium ions was utilized as an anticoagulant for treating severely affected patients. By adjusting the citrate anticoagulant dose and monitoring treatment indicators, RCA-CRRT parameters were actively modified to alleviate the hypercalcemia crisis and provide time for surgery or specialized treatment. Two patients experienced rapid and effective reductions in blood calcium levels, allowing for further treatment, while the third patient exhibited a repeated increase in blood calcium, which eventually decreased after parathyroid adenoma resection, leading to clinical discharge. Our findings suggest that RCA-CRRT can help alleviate hypercalcemia crisis, stabilize the patient's internal environment, and provide valuable time for clinical treatment in cases of various medical conditions causing abnormal blood calcium elevations.

3.
Ren Fail ; 45(2): 2271069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37870850

RESUMO

BACKGROUND: Cardiovascular calcification includes cardiac valve calcification (CVC) and vascular calcification. We aimed to analyze risk factors for CVC, and construct a predictive model in maintenance peritoneal dialysis (MPD) patients. METHODS: We retrospectively analyzed MPD patients who began peritoneal dialysis between January 2014 and September 2021. Patients were randomly assigned to the derivation cohort and validation cohort in a 7:3 ratio. The patients in the derivation cohort were divided into the CVC group and non-CVC group. Logistic regression was used to analyze risk factors, then the rms package in R language was used to construct a nomogram model to predict CVC. RESULTS: 1,035 MPD patients were included, with the age of 50.0 ± 14.2 years and 632 males (61.1%). Their median follow-up time was 25 (12, 46) months. The new-onset CVC occurred in 128 patients (12.4%). In the derivation cohort, multivariate logistic regression indicated old age, female, high systolic blood pressure (SBP), high calcium-phosphorus product (Ca × P), high Charlson comorbidity index (CCI) and long dialysis time were independent risk factors for CVC (p < 0.05). We constructed a nomogram model for predicting CVC in the derivation cohort, with a C index of 0.845 (95% CI 0.803-0.886). This model was validated with a C index of 0.845 (95%CI 0.781-0.909) in the validation cohort. CONCLUSION: We constructed a nomogram model for CVC in MPD patients, using independent risk factors including age, sex, SBP, Ca × P, CCI and dialysis time. This model achieved high efficiency in CVC prediction.


Assuntos
Doenças das Valvas Cardíacas , Diálise Peritoneal , Calcificação Vascular , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças das Valvas Cardíacas/etiologia , Diálise Peritoneal/efeitos adversos , Calcificação Vascular/etiologia , Fatores de Risco , Valvas Cardíacas
4.
Ren Fail ; 45(1): 2175590, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36856148

RESUMO

Background: Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods: In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 µg, 2.5 µg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results: A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 µg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 µg and placebo group was 8.81 mm, but not statistically significantly different. Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5µg, 38.6% in 2.5 µg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions: Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Rim , Insuficiência Renal Crônica/complicações , Prurido/tratamento farmacológico , Prurido/etiologia
5.
J Nephrol ; 34(5): 1569-1580, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34173939

RESUMO

BACKGROUND: The effect of urolithiasis on pregnancy-related outcomes remains unknown. The aim of this study was to determine the risk of adverse maternal and neonatal outcomes. METHODS: We searched PubMed, Embase, and the Cochrane Library through December 2020 for studies reporting on adverse maternal and neonatal outcomes in patients with urolithiasis. Risk ratios (ORs) with 95% confidence intervals (CIs) were calculated for these outcomes in pregnant mothers with urolithiasis and compared to healthy controls. RESULTS: Eight studies comprising 26,577 mothers with urolithiasis were included in our analysis. Preterm birth (OR = 1.63; 95% CI 1.37-1.95, p < 0.001) or very preterm birth risk (OR = 1.49, 95% CI 1.06-2.11, p = 0.02) was more common in patients with urolithiasis compared to healthy controls. Mothers with urolithiasis had an increased incidence of preeclampsia (OR = 1.75, 95% CI 1.33-2.3, p < 0.001), hypertension (OR = 2.97, 95% CI 1.31-6.71, p = 0.009), caesarean section (OR 1.31, 95% CI 1.11-1.55, p = 0.001), and gestational diabetes mellitus (OR 1.84, 95% CI 1.37-2.46, p < 0.001). CONCLUSION: Patients with urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes.


Assuntos
Diabetes Gestacional , Nascimento Prematuro , Urolitíase , Cesárea , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Urolitíase/diagnóstico , Urolitíase/epidemiologia
6.
Nutr Metab (Lond) ; 16: 52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31388342

RESUMO

BACKGROUND: The results remain controversial with regards to the impact of serum uric acid on clinical outcomes from peritoneal dialysis population. The aim of our study was to investigate the influence of serum uric acid levels on mortality in peritoneal dialysis patients. METHODS: Data on 9405 peritoneal dialysis patients from the Zhejiang Renal Data system were retrospectively analyzed. All demographic and laboratory data were recorded at baseline. The study cohort was divided into quintiles according to baseline uric acid level (mg/dL): Q1 (< 6.06), Q2 (6.06-6.67), Q3 (6.68-7.27) (reference), Q4 (7.28-8.03), and Q5 (≥8.04). Hazards ratio (HR) of all-cause and cardiovascular mortality was calculated. RESULTS: Mean serum uric acid was 7.07 ± 1.25 mg/dL. During a median follow-up of 29.4 (range, 3.0 to 115.4) months, 1226 (13.0%) patients died, of which 515 (5.5%) died of cardiovascular events. The Kaplan-Meier survival curves showed that patients in the middle uric acid quintile (Q3: 6.68-7.27) exhibited the highest patient and cardiovascular survival rates (log-rank test P < 0.05). Multivariate Cox regression analysis showed that, using Q3 as the reference, in the fully adjusted model, a higher uric acid level (Q4: 7.28-8.03, and Q5: ≥8.04) was significantly associated with higher all-cause mortality (Model 3; Q4: HR, 1.335, 95% CI, 1.073 to 1.662, P = 0.009; Q5: HR, 1.482, 95% CI, 1.187 to 1.849, P = 0.001), but not with cardiovascular mortality. The adverse effect of higher uric acid level (≥7.28 mg/dL) on all-cause mortality was more prominent in groups such as male, hypoalbuminemia, normal weight, non-diabetes mellitus at baseline rather than in their counterparts respectively. CONCLUSIONS: A higher uric acid level was an independent risk factor for all-cause mortality in peritoneal dialysis patients.

7.
BMC Nephrol ; 20(1): 128, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975091

RESUMO

BACKGROUND: Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear. METHODS: We select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival. RESULTS: One hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival. CONCLUSIONS: We found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.


Assuntos
Líquido Ascítico/imunologia , DNA Mitocondrial/análise , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritonite , Adulto , Biomarcadores/análise , Soluções para Diálise/análise , Feminino , Humanos , Interleucina-17/análise , Interleucina-6/análise , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Peritonite/etiologia , Peritonite/imunologia , Fatores de Necrose Tumoral/análise
8.
Kidney Blood Press Res ; 42(6): 1225-1237, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29248920

RESUMO

BACKGROUND/AIMS: The presence of protein-energy wasting (PEW) among dialysis patients is a crucial risk factor for outcomes. The complicated pathogenesis of PEW makes it difficult to assess and treat. This single-center retrospective study focuses on the association between nutritional markers and the outcomes of continuous ambulatory peritoneal dialysis(CAPD) patients, aiming to establish a practical comprehensive nutritional scoring system for CAPD patients. METHODS: 924 patients who initiated peritoneal dialysis in our center from January 1st,2005 to December 31st,2015 were enrolled. Comprehensive nutritional scoring system(CNSS) was based on items including SGA, BMI, ALB, TC, MAC and TSF. We divide patients into 3 groups according to their CNSS score. Outcomes including mortality, hospitalization days and hospitalization frequency were compared between 3 grades. RESULTS: The CNSS grade correlated significantly with hospitalization days (P<0.05). Both categorized CNSS grade (HR:0.56; 95% CI:0.41-0.78; P = 0.001) and continuous CNSS score (HR:0.87; 95% CI: 0.80-0.94; P = 0.001) independently protect PD patients from all-cause mortality. CONCLUSION: CNSS provides an integrated scoring system with significant associations with hospitalization and mortality in PD patients. The CNSS grade differentiates patients with malnutritional risk and independently predicts high risk of morbidity and mortality.


Assuntos
Falência Renal Crônica/diagnóstico , Estado Nutricional , Diálise Peritoneal Ambulatorial Contínua , Adulto , Idoso , Feminino , Hospitalização , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Desnutrição Proteico-Calórica , Estudos Retrospectivos , Resultado do Tratamento
9.
Kidney Blood Press Res ; 42(6): 1266-1276, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29248923

RESUMO

BACKGROUND/AIMS: Studies on the risk factors and outcomes of peritonitis within the first 6 months in peritoneal dialysis patients are sparse. This study aims to investigate the risk factors associated with early-onset peritonitis (EOP) and its influence on patients' technique survival and mortality. METHODS: This is a retrospective observational cohort study. A total of 483 patients who had at least one episode of peritonitis were enrolled and followed from March 1, 2002, to August 31, 2016, at our center. According to the time to first peritonitis, we divided patients into two groups: EOP (≤ 6 months, n=167) and late-onset peritonitis (LOP, >6 months, n=316). Logistic regression was used to analyze the factors associated with EOP. A Cox proportional hazards model was constructed to examine the influence of EOP on clinical outcomes. RESULTS: Of the 483 patients, 167 (34.6%) patients developed their first episode of peritonitis within the first 6 months. The EOP patient group had more male patients, a shorter time on peritoneal dialysis (PD), lower serum albumin levels at the time of PD initiation and a higher peritonitis rate (P<0.05). The EOP patient group had fewer infections with Gram-negative organisms (P=0.013) and more culture-negative peritonitis (P=0.014) than the LOP patient group for the first episode of peritonitis. The multivariate logistic regression analysis showed that factors associated with EOP included male gender (odds ratio (OR) 1.920, 95% confidence interval (CI) 1.272-2.897, P=0.002) and a low serum albumin level at the start of PD (OR 0.950, 95% CI 0.914-0.986, P=0.007). In the Cox proportional hazards model, EOP was a significant predictor of all-cause mortality (hazard ratio (HR) 2.766, 95% CI 1.561-4.900, P<0.001). There were no differences between EOP and LOP for technique failure. However, in continuous analyses, a negative correlation was observed between the time to first peritonitis and technique failure (HR 0.988, 95% CI 0.980-0.997, P=0.006). In the Spearman analysis, the time to first peritonitis was negatively correlated with the peritonitis rate (r=-0.573, P<0.001). CONCLUSION: Male gender and a low serum albumin level before PD were strongly associated with EOP. Additionally, EOP patients had a higher risk of poor clinical outcomes. More importantly, an early peritonitis onset was associated with a high peritonitis rate.


Assuntos
Diálise Peritoneal/efeitos adversos , Peritonite/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peritonite/terapia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
10.
Kidney Blood Press Res ; 42(1): 52-61, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28315872

RESUMO

BACKGROUND/AIMS: Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Little is known about the relationship between very low-density lipoprotein cholesterol (VLDL-C) and cardiovascular mortality in these patients. METHODS: A total of 1324 incident patients who began continuous ambulatory peritoneal dialysis (CAPD) therapy at our hospital between January 1, 2005, and September 30, 2014, with baseline serum VLDL-C values were investigated. The associations of the VLDL-C levels with all-cause and cardiovascular mortality were assessed. RESULTS: The mean age of the cohort was 50.2 ± 14.8 years, and the mean VLDL-C level was 33.6 ± 18.0 mg/dl. One hundred sixty-five (12.5%) patients died during the study period. Multivariable models revealed that the high VLDL-C group was associated with significantly higher all-cause (HR, 2.08, 95% CI, 1.13 to 3.29, P = 0.002) and cardiovascular mortality (HR, 1.92, 95% CI, 1.18 to 4.29, P = 0.013) compared with the low VLDL-C group even after adjusting for various covariates. Using the VLDL-C level as a continuous variable, the hazard ratios (HRs) of all-cause and cardiovascular mortality associated with a 10-mg/dl increase in VLDL-C level were 1.12 (95% CI, 1.02 to 1.26, P = 0.025) and 1.11 (95% CI, 1.02 to 1.22, P = 0.029), respectively. VLDL-C was associated more strongly to all-cause (e.g., Akaike information criteria of 1990.205 vs. 1994.451) and cardiovascular (e.g., Akaike information criteria of 984.146 vs. 985.634) mortality than triglyceride (TG) levels. CONCLUSIONS: An elevated VLDL-C level is an independent risk factor for all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.


Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , VLDL-Colesterol/sangue , Diálise Peritoneal/mortalidade , Adulto , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Fatores de Risco
11.
Medicine (Baltimore) ; 95(49): e5569, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27930566

RESUMO

Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients' technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients.This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes.During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality.We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality.These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes.


Assuntos
Causas de Morte , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/etiologia , Peritonite/mortalidade , Adulto , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Diálise Peritoneal Ambulatorial Contínua/métodos , Peritonite/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
12.
J Zhejiang Univ Sci B ; 17(5): 375-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27143265

RESUMO

To describe the long-term clinical outcomes of patients with autosomal dominant polycystic kidney disease (ADPKD) who are on peritoneal dialysis (PD) therapy. We performed a retrospective matched-cohort analysis comparing the clinical outcomes of 30 ADPKD patients with those of 30 non-diabetic patients who had bilateral small kidneys between July 1 2007 and July 31 2014. The patient groups were matched by age, gender, and time of PD initiation. There were no significant differences in the demographic or biochemical parameters, comorbid conditions, residual glomerular filtration rate, or Charlson comorbidity score at the beginning of PD. The median renal volume was 1315 ml for the ADPKD group and 213 ml for the control group. Patients with ADPKD had similar 3-year patient survival (90.6% versus 86.3%, P=0.807) and technique survival (89.2% versus 74.3%, P=0.506) compared with non-ADPKD patients. Also, there was no significant difference in the peritonitis-free survival between the ADPKD and control groups (P=0.22), and rates of peritonitis were similar (0.19 versus 0.21 episodes per patient-year, P=0.26). No differences were observed in the incidence of PD-related complications, such as hernia and dialysate leak. ADPKD is not a contraindication for PD, and a subgroup of ADPKD patients with relatively small kidney volume can be treated using PD.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal , Rim Policístico Autossômico Dominante/terapia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Intervalo Livre de Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Estimativa de Kaplan-Meier , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
FEBS J ; 283(12): 2309-25, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27093550

RESUMO

Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Rapamycin has been previously shown to inhibit EMT of PMCs and prevent peritoneal fibrosis. In this study, we investigated the undefined molecular mechanisms by which rapamycin inhibits EMT of PMCs. To define the protective effect of rapamycin, we initially used a rat PD model which was daily infused with 20 mL of 4.25% high glucose (HG) dialysis solution for 6 weeks to induce fibrosis. The HG rats showed decreased ultrafiltration volume and obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-smooth muscle actin (α-SMA) and transforming growth factor-ß1. Rapamycin significantly ameliorated those pathological changes. Next, we treated rat PMCs with HG to induce EMT and/or rapamycin for indicated time. Rapamycin significantly inhibited HG-induced EMT, which manifests as increased expression of α-SMA, fibronectin, and collagen I, decreased expression of E-cadherin, and increased mobility. HG increased the phosphorylation of PI3K, Akt, and mTOR. Importantly, rapamycin inhibits the RhoA, Rac1, and Cdc42 activated by HG. Moreover, rapamycin repaired the pattern of F-actin distribution induced by HG, reducing the formation of stress fiber, focal adhesion, lamellipodia, and filopodia. Thus, rapamycin shows an obvious protective effect on HG-induced EMT, by inhibiting the activation of Rho GTPases (RhoA, Rac1, and Cdc42).


Assuntos
Fibrose Peritoneal/tratamento farmacológico , Sirolimo/administração & dosagem , Proteína cdc42 de Ligação ao GTP/biossíntese , Proteínas rac1 de Ligação ao GTP/biossíntese , Proteína rhoA de Ligação ao GTP/biossíntese , Animais , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Epitélio/patologia , Fibronectinas , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/toxicidade , Humanos , Fibrose Peritoneal/induzido quimicamente , Fibrose Peritoneal/genética , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Peritônio/patologia , Ratos , Proteína cdc42 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/genética
14.
BMC Nephrol ; 16: 91, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26126806

RESUMO

BACKGROUND: A number of studies have provided information regarding the risks and benefits of mammalian target of rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA). METHODS: Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials comparing mTOR-I to MPA as the primary immunosuppressive regimen in combination with CNI were selected and meta-analyzed. RESULTS: Eleven randomized controlled trials consisting of 4930 patients in total were included. No significant difference was observed in the risk of biopsy-proven acute rejection and patient death between the two groups. However, an increased risk of graft loss (relative risk (RR) = 1.20) and inferior graft function (creatinine clearance, weighted mean difference (WMD) = -2.41 µmol/L) were demonstrated in mTOR-I-treated patients. Patients treated with mTOR-I had a higher risk of new-onset diabetes mellitus (RR = 1.32), dyslipidemia, proteinuria (RR = 1.79), peripheral edema (RR = 1.34), thrombocytopenia (RR = 1.97) and lymphocoele (RR = 1.80), but a lower risk of cytomegalovirus infection (RR = 0.40), malignancy (RR = 0.64) and leucopenia (RR = 0.43). There was no difference in diarrhea, anemia, urinary tract infection, polyoma virus infection and impaired wound healing when mTOR-I was compared with MPA. CONCLUSIONS: mTOR-I showed no particular superiority to MPA. Notably, mTOR-I had an increased risk of graft loss when combined with CNI, even when combined with a reduced dose of CNI. Therefore, the optimal dosage strategies for mTOR-I and CNI need to be further explored.


Assuntos
Corticosteroides/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Everolimo/uso terapêutico , Humanos , Ácido Micofenólico/uso terapêutico , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
15.
Oncotarget ; 6(19): 17016-30, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26219259

RESUMO

T cells play a critical role in acute allograft rejection. TGF-ß/Smad3 signaling is a key pathway in regulating T cell development. We report here that Smad3 is a key transcriptional factor of TGF-ß signaling that differentially regulates T cell immune responses in a mouse model of cardiac allograft rejection in which donor hearts from BALB/c mice were transplanted into Smad3 knockout (KO) and wild type (WT) mice. Results showed that the cardiac allograft survival was prolonged in Smad3 KO recipients. This allograft protection was associated with a significant inhibition of proinflammatory cytokines (IL-1ß, TNF-α, and MCP-1) and infiltration of neutrophils, CD3+ T cells, and F4/80+ macrophages. Importantly, deletion of Smad3 markedly suppressed T-bet and IFN-γ while enhancing GATA3 and IL-4 expression, resulting in a shift from the Th1 to Th2 immune responses. Furthermore, mice lacking Smad3 were also protected from the Th17-mediated cardiac injury, although the regulatory T cell (Treg) response was also suppressed. In conclusion, Smad3 is an immune regulator in T cell-mediated cardiac allograft rejection. Loss of Smad3 results in a shift from Th1 to Th2 but suppressing Th17 immune responses. Thus, modulation of TGF-ß/Smad3 signaling may be a novel therapy for acute allograft rejection.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Coração , Proteína Smad3/imunologia , Linfócitos T/imunologia , Imunologia de Transplantes/imunologia , Aloenxertos , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Subpopulações de Linfócitos T/imunologia
16.
Atherosclerosis ; 222(1): 29-33, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22417842

RESUMO

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated with accelerated atherosclerosis independent of traditional risk factors. Statins, the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been widely prescribed for hyperlipidemia, which could slow the atherosclerosis progression, and reduce cardiovascular disease events. Nonetheless, accumulated evidences suggested that statins exert immunomodulatory and anti-inflammatory functions independent of their lipid-lowering effects. By the virtue of pleiotropic immunomodulatory property, statins may be applied for the treatment of both autoimmunity and atherosclerosis in patients with SLE. Interestingly, it has been well documented that regulatory T cells (Tregs) are involved in the pathogenesis of SLE as well as atherosclerosis. Meanwhile, studies have shown that statins could induce augmented number of Tregs with increased functional inhibitory properties. Thus, we hypothesized that the effect of statins ameliorating lupus disease manifestations and lupus-mediated atherogenesis might be mediated, at least partly, via the activation of Tregs. To our knowledge, this is the first hypothesis focused on that Tregs might be involved in the immunomodulatory effect of statins on SLE and SLE-related atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Animais , Aterosclerose/etiologia , Aterosclerose/imunologia , Humanos , Fatores Imunológicos/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Reguladores/efeitos dos fármacos
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