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Objective To investigate the epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients and analyze the risk and protective factors of severe/critical infection with SARS-CoV-2. Methods Clinical data of 468 kidney transplant recipients infected with SARS-CoV-2 were retrospectively analyzed. According to the severity of infection, they were divided into mild SARS-CoV-2 infection recipients (n=439) and SARS-CoV-2 pneumonia group (n=29). Among the 439 mild SARS-CoV-2 infection recipients, 87 recipients who were randomly matched with their counterparts in the SARS-CoV-2 pneumonia group according to sex, age and transplantation time at a ratio of 3∶1 were allocated into the mild SARS-CoV-2 infection group. Twenty-nine recipients in the SARS-CoV-2 pneumonia group were divided into the moderate SARS-CoV-2 pneumonia group (n=21) and severe/critical SARS-CoV-2 pneumonia group (n=8). Baseline data of all recipients were collected. The risk and protective factors of SARS-CoV-2 infection in kidney transplant recipients were identified. Results The proportion of recipients complicated with 2-3 types of complications in the SARS-CoV-2 pneumonia group was higher than that in the mild SARS-CoV-2 infection group, and the proportion of recipients treated with tacrolimus(Tac)+mizoribine+glucocorticoid immunosuppression regimen in the SARS-CoV-2 pneumonia group was lower than that in the mild SARS-CoV-2 infection group, and significant differences were observed (both P<0.05). In 29 kidney transplant recipients with SARS-CoV-2 pneumonia in the SARS-CoV-2 pneumonia group, white blood cells, the absolute values of lymphocytes, eosinophils, total T cells, CD4+T cells and CD8+T cells, and serum uric acid levels were significantly lower, whereas ferritin levels were significantly higher than the values prior to SARS-CoV-2 pneumonia, and significant differences were observed (all P<0.05). Compared with the moderate SARS-CoV-2 pneumonia group, the proportion of recipients with hypoxemia was higher, the proportion of recipients treated with Tac/ciclosporin (CsA)+mycophenolate mofetil+glucocorticoid immunosuppression regimen was higher, and the proportion of recipients administered with 2-3 doses of SARS-CoV-2 vaccine was lower in the severe/critical SARS-CoV-2 pneumonia group, and significant differences were observed (all P<0.05). Conclusions More complications and immunosuppression regimen containing mycophenolate mofetil are the risk factor for SARS-CoV-2 infection in kidney transplant recipients. Vaccination with SARS-CoV-2 vaccine and immunosuppression regimen containing mizoribine are probably the protective factors for lowering the risk of SARS-CoV-2 infection. The levels of inflammatory cytokines are associated with the severity of SARS-CoV-2 pneumonia.
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OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.
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Male , Animals , Mice , Mice, Inbred C57BL , Mycophenolic Acid/therapeutic use , Carbon Tetrachloride/toxicity , Transforming Growth Factor beta1/genetics , Liver Cirrhosis/drug therapy , RNA, MessengerABSTRACT
Immunoglobulin G4-related diseases(IgG4-RD)are chronic, systemic diseases that have received much attention in recent years. IgG4-RD can affect almost all tissues of the body, mainly manifested by swelling and space-occupying changes in the involved sites. It is called IgG4-related ophthalmic disease(IgG4-ROD)when the lesions invade the ocular area. The disease mainly invades the lacrimal glands, orbital fat, infraorbital nerve, extraocular muscles, and eyelids. At present, the main treatment modalities for IgG4-ROD include medication, surgery, and radiation therapy, etc. With the enhanced understanding of the disease and the increasing cure rate in recent years, this article reviews the latest progress in the epidemiological characteristics, clinical manifestations, imaging features, diagnosis and treatment of IgG4-ROD.
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Objective:To assess the efficacy of Rituximab (RTX) in treating children with refractory nephro-tic syndrome.Methods:A retrospective study was carried out.Twenty-two children diagnosed with refractory nephrotic syndrome in the Department of Nephrology of Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2018 to November 2020 were included in the study.All patients were treated with RTX.Patients with CD 19+ B lymphocytes≥1% total lymphocytes in peripheral blood were supplemented with one dose of RTX (375 mg/m 2), and each patient received 3-4 doses of RTX on average.The patients were treated with Mycophenolate mofetil after early discontinuation of calcineurin inhibitors (CNI). The Kaplan-Meier method was used to analyze the proteinuria relapse-free rate and the incidence of frequently recurrent nephrotic syndrome or steroid-dependent nephrotic syndrome in children after RTX treatment.The relapse times before and after using RTX were analyzed by the Wilcoxon signed rank test.Besides, the body mass indexes (BMI) and height of children before and after RTX treatment were compared by the rank sum test. Results:Of 22 patients studied, 20 patients accomplished the therapeutic protocol.One-year and two-year proteinuria relapse-free survival rates were 85% and 40%, respectively.The recurrence rate was reduced under the discontinuation of CNI.Compared with those before RTX treatment, the BMI and height of all children were significantly improved at 1 year and 2 years after RTX treatment (all P<0.05). However, no significant improvement was observed between 1 or 2 years after RTX treatment (all P>0.05). Conclusions:The use of RTX can effectively reduce the recurrence rate of refractory nephrotic syndrome even when hormones and other immunosuppressants are discontinued.At the same time, RTX can significantly improve the BMI and height of children.RTX is safe and effective for treatment of refractory nephrotic syndrome.
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Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease that is closely related to thyroid dysfunction. It is one of the most common orbital diseases in adults with complex clinical manifestations. As the disease progresses, it may manifest as proptosis, diplopia, exposure keratitis, corneal ulceration and compressive optic neuropathy, leading to irreversible visual impairment or even blindness. The treatment is lack of specificity and only focuses on clinical symptomatic treatment, the efficacy is uncertain. It is currently a problematic area of ophthalmology. Clinical first-line drug treatment is based on glucocorticoids. Second-line treatments, such as immunosuppressants and radiotherapy, all them have certain limitations. With the in-depth and comprehensive understanding of the disease, a variety of new targeted drugs represented by teprotumumab and rituximab have been developed for the pathogenesis of TAO. Their excellent roles in relieving inflammation and controlling the disease are the future research direction. In this paper, the current status and research progress of conservative treatment of TAO will be reviewed.
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The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification.
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@#AIM: To evaluate the efficacy of mycophenolate mofetil(MMF)on the prevention of relapse and visual prognosis of patients in neuromyelitis optica spectrum disorders(NMOSD)with AQP4 antibody positive optic neuritis. <p>METHODS: We retrospectively reviewed 11 patients with initial diagnosis of NMOSD and AQP4 antibody positive optic neuritis from January 2017 to December 2019. Among the 11 patients, 3 were male and 8 were female. The unique core clinical manifestation of NMOSD was optic neuritis. The onset age was 36.3±6.0(27-47)years old. Duration of the disease was 3.4±1.4(2.2-6.8)a. MMF was added in the relieving period of NMOSD for 1a or over 1a. Annualized relapsing rate(ARR), best corrected vision activity(BCVA)and adverse reactions of MMF were recorded.<p>RESULTS: The median time of MMF treatment was 18(12, 36)mo. The ARR was 0.66/a at baseline and 0.16/a after the treatment. There were 91% of the patients had decreased ARR and 82% of them had no clinical relapse. The patients had significant improvement on ARR after MMF treatment(<i>P</i><0.05 ). In total, there was no significant difference between the mean BCVA after treatment and that at baseline(<i>P</i>>0.05). Of the 11 patients, 3 patients had side effects(27%), including 1 patient with elevated liver transaminase(9%), and 2 patients with mild gastrointestinal reaction(18%)during follow-up period. None of them discontinued MMF due to adverse events.<p>CONCLUSION: MMF treatment for AQP4 antibody positive NMOSD can reduce the ARR of optic neuritis to a certain extent and protect the visual function of patients.
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OBJECTIVE To com pare the long-term efficacy and safety betwe en domestic Mycophenolate mofetil dispersible tablets（dt-MMF）and imported Mycophenolate mofetil capsules （c-MMF）in kidney transplant recipients. METHODS In retrospective cohort study ，the data of patients who had undergone the living donor kidney transplantat during the period of 2012 to 2014 in West China Hospital of Sichuan University were screened and included ，and then divided into dt-MMF group and c-MMF group according to the drug use of kidney transplant recipients. Initial oral dose of dt-MMF and c-MMF were both 1 000 mg each time ， twice a day ；at the same time ，both groups were additionally given Tacrolimus capsules 1.5 mg，twice a day+Prednisone acetate tablets 5-10 mg，orally after breakfast every day. The clinical data of the two groups were collected before and after kidney transplant for 5 years；the efficacy and safety indexes of two drugs were compared ，and the robustness of results were analyzed by 1∶1 propensity score matching （PSM）. RESULTS A total of 666 kidney transplant recipients were included ，involving 316 patients in dt-MMF group and 350 patients in c-MMF group. The 5-year patient survival rates of dt-MMF group and c-MMF group were 99.68％ and 99.43％，the 5-year graft survival rates were 96.20％ and 94.29％，the acute rejection rates were 3.80％ and 6.57％，the 5-year chronic rejection rates were 2.22％ and 2.86％，and the incidences of delayed recovery of transplanted renal function were 0.63％ and 0.29％，respectively；there was no statistical significance （P＞0.05）. There were no significant differences in the incidence of major adverse events between 2 groups，including infection ，adverse events of the blood system and diges tive system （P＞0.05）. PSM analysis indicated the efficacy and safety results were robust （except for acute rejection ）. CONCLUSIONS There is no significant difference in clinical efficacy and safety between dt-MMF and c-MMF for immunosuppression after kidney transplant.
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Objective To investigate the exposure difference of different dosage forms of mycophenolic acid (MPA) between children aged ≤12 and > 12 years old after kidney transplantation. Methods Clinical data of 73 children undergoing kidney transplantation from donation after cardiac death (DCD) were retrospectively analyzed. Postoperative immunosuppressive regimen was MPA+ tacrolimus+glucocorticoid. According to different dosage forms of MPA, all recipients were divided into group A (n=37, mycophenolate mofetil capsules), group B (n=28, enteric-coated mycophenolate sodium) and group C (n=8, mycophenolate mofetil dispersible tablets). All children were divided into ≤12 and > 12 years old groups according to the age of kidney transplantation. The daily dosage of different dosage forms was calculated. The blood concentration (C) of MPA and the area under the curve (AUC) were detected by enzyme-multiplied immunoassay technique. The MPA blood concentration was statistically compared between two age groups at different time points. The recovery of renal function and postoperative complications were assessed. Results No significant differences were observed in the dosage and blood concentration of drug at different time points among groups A, B and C (all P > 0.05). The MPA-C4 h and AUC in the ≤12 years old group were significantly higher than those in the > 12 years old group (both P < 0.05). In group B, the MPA-C4 h of children aged ≤12 years old was significantly higher compared with that in those aged > 12 years old (P=0.016). The MPA-C4 h of children aged ≤12 years old in group B was higher than those in group A and group C, but the differences were not statistically significant (P=0.080). There was no significant difference in the incidence of acute rejection and infection among three groups (both P > 0.05). Conclusions Children of different ages who are given with different dosage forms of MPA after kidney transplantation obtain different exposure rates. The exposure rate of kidney transplant recipients aged ≤12 years old tends to be higher than that of their counterparts aged > 12 years old, mainly seen in the recipients treated with enteric-coated mycophenolate sodium. Therefore, it is necessary to monitor the exposure level of MPA, which provides significant guidance for adjusting the drug dosage of different dosage forms.
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Objective:To summarize clinical features, outcome and prognosis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders (MOGAD) in children, and to explore the markers of recurrent MOGAD.Methods:The clinical features, imaging, serum and cerebrospinal fluid immune markers, treatments and outcomes were analyzed and compared between children with monophasic and recurrent MOGAD, who were hospitalized in the Department of Neurology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics from January 2019 to February 2020.Results:A total of 22 children were included, of whom 8 patients (36.4%) had a recurrent course and 14 patients (63.6%) had a monophasic course. There was no statistically significant difference in sex, age of onset, clinical symptoms, modified Rankin Scale score, location of lesions and serum anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) titer, overall duration of total immunotherapy, positive antinuclear antibody and history of precursory infection between the two groups ( P>0.05). The serum MOG-IgG titer in the recurrent course group was more likely to remain unchanged or increased, and even increased after treatment, while there was no increase in the serum MOG-IgG titer in the monophasic course group, and the proportion of the patients with serum MOG-IgG titer decreased was higher in the monophasic course group (the monophasic course group: 6/8, the recurrent course group: 2/8), and there was statistically significant difference between the two groups ( P=0.030). The positive rate of MOG-IgG in cerebrospinal fluid in the recurrent course group was significantly higher than that in the monophasic course group at the first attack, the difference being statistically significant (the monophasic course group: 1/10, the recurrent course group: 4/6, P=0.036). The both groups were effecive to first-line immunotherapy, and the clinical symptoms and imaging were completely or partially recovered compared to the acute phase. Seven of 8 patients with recurrent MOGAD were treated with mycophenolate mofetil, and the recurrence rate decreased significantly [annual recurrence rate before treated with mycophenolate mofetil: 2.06 (1.36, 2.34) times/year, annual recurrence rate after treated with mycophenolate mofetil: 0 (0, 0) time/year, Z=-3.26, P=0.001]. The humoral immune status of children treated with mycophenolate mofetil was monitored regularly, and no obvious adverse reactions were found during the follow-up. Conclusions:At least one third of children with MOGAD were recurrent, and the serum MOG-IgG titer of children with recurrent MOGAD continued to be high, and even increased after treatment. Positive MOG-IgG in cerebrospinal fluid at the first attack was found to be a high risk factor for recurrence. The maintenance treatment of mycophenolate mofetil in patients with recurrent MOGAD can significantly reduce the annual recurrence rate and was well tolerated.
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ABSTRACT Objective: Encapsulating peritoneal sclerosis (EPS) is a rare, but potentially fatal complication of peritoneal dialysis. Currently, treatment of peritoneal fibrosis is not fully possible yet. In this study, we aimed to demonstrate the effects of tacrolimus therapy on peritoneal fibrosis and inflammation when administered alone or with mycophenolate mofetil (MMF) in the EPS model induced in rats. Methods: Thirty six Wistar albino rats were separated into six equal groups. Group I was the control group. Group II-VI were administered intraperitoneal chlorhexidine (CH) for induced EPS model in rats. Group II, IV, V, VI were administered isotonic liquid, tacrolimus, tacrolimus and concurrently with CH, tacrolimus and MMF together, respectively. Group III was not administered any drug. All peritoneal samples were stained immunohistochemically with matrix metalloproteinase-2 (MMP-2) antibody. Thickness of peritoneal fibrosis, subserosal large collagen fibers, subserosal fibroblast proliferation and subserosal fibrotic matrix deposition were evaluated. Results: Comparing the experimentally induced EPS groups, the best histopathological results and the largest staining with MMP-2 were achieved in Group VI. Furthermore, in all treatment groups (IV, V, VI) more staining with MMP-2 was detected compared to non-treatment groups (I, II, III) but no statistically significant differences were found among all groups. A statistically significant remission was observed in all histopathological parameters, primarily peritoneal thickness in rats that were administered MMF with tacrolimus, compared to rats which were administered tacrolimus only. Conclusion: Concurrent use of tacrolimus and MMF in the treatment of EPS may be a promising approach.
RESUMEN Objetivos: La esclerosis peritoneal encapsulante (EPE) es una complicación rara, peropotencialmente fatal de la diálisis peritoneal. Actualmente, el tratamiento de la fibrosis peritoneal aún no es posible. En este estudio, apuntamos a demostrar los efectos de la terapia con tacrolimus en la fibrosis peritoneal y la inflamación cuando se administran solos o con micofenolato de mofetilo (MMF) en el modelo EPE inducido en ratas. Métodos: Treinta y seis ratas Wistar albinas se separaron en seis grupos iguales. El Grupo I era el grupo de control. En los grupos II-VI se administró clorhexidina intraperitoneal (CH) para el modelo EPE inducido en ratas. En los Grupos II, IV, V, VI se administró respectivamente líquido isotónico, tacrolimus, tacrolimus y CH y finalmente tacrolimus y MMF juntos. El grupo III no recibió ningún medicamento. Todas las muestras peritoneales se tiñeron inmunohistoquímicamente con el anticuerpo Matrix Metaloproteinasa-2 (MMP- 2). Se evaluó el grosor de la fibrosis peritoneal, se evaluaron las fibras de colágeno grandes subserosas, la proliferación de fibroblastos subserosa y la deposición de la matriz fibrótica subserosa. Resultados: Comparando los grupos de EPE inducidos experimentalmente, los mejores resultados histopatológicos y la tinción con MMP- 2 más extensa se lograron en el Grupo VI. Además, en todos los grupos de tratamiento (IV, V, VI) se detectó más tinción con MMP-2 en comparación con los grupos de no tratamiento (I, II, III), pero no se encontraron diferencias estadísticamente significativas entre todos los grupos. Se observó una remisión estadísticamente significativa en todos los parámetros histopatológicos, principalmente el espesor peritoneal en ratas que recibieron MMF con tacrolimus, en comparación con las ratas que recibieron solo tacrolimus. Conclusión: El uso concurrente de tacrolimus y MMF en el tratamiento de EPS puede ser una aplicación prometedora.
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Objective:To evaluate the efficacy and safety of mycophenolate mofetil(MMF) in patients with active moderate to severe thyroid associated ophthalmopathy(TAO) refractory to multiple intravenous glucocorticoid(GC).Methods:Fifty-two patients with active moderate to severe TAO that was refractory to multiple intravenous GC were treated with MMF 0.5g orally, 2/d. To evaluate the overall response rate of TAO patients, the improvement of more than 3 items including clinical disease activity score(CAS), soft tissue involvement, proptosis, diplopia, decrease of eye movements, visual acuity and other improvements were defined as response.Results:After 12 weeks of MMF treatment, the overall response rate of TAO patients was 75.0%, and then increased to 88.5% significantly at the 24th weeks. At the 12th weeks, CAS decreased from(5.06±1.21) to(2.52±1.13), and then continued to decrease to(2.02±0.92) at the 24th week( P<0.05), the response rates were 82.7% and 90.4%, respectively. In addition, after 12 weeks of treatment, 58.1% of patients with diplopia improved significantly, and the response rate was 74.2% at the 24th weeks. Similarly, the degree of proptosis decreased significantly at the 12th and 24th weeks, and the response rates were 53.8% and 69.2%, respectively. No serious adverse events occurred during the treatment. Conclusion:The MMF therapy is efficient and safe for patients with active moderate to severe corticosteroid-resistant TAO.
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Objective:To compare the efficacy and safety of leflunomide(LEF)to mycophenolate mofetil(MMF)and cyclophosphamide(CTX)in the treatment of Henoch-Sch?nlein purpura nephritis(HSPN)in children with nephrotic proteinuria.Methods:Thirty-nine children who were diagnosed as HSPN with nephrotic proteinuria were randomly divided into three groups: LEF group, MMF group and CTX group.Each group had 13 children.Proteinuria, hematuria, adverse effect and cost were followed up at 1, 3, 6 and 9 months of medication.Results:Proteinuria and hematuria were significantly decreased in each group at 1, 3, 6 and 9 months of medication.Compared to CTX group, proteinuria and hematuria in LEF group and MMF group were lower at 9 months.It was probably associated with one child whose proteinuria did not completely return to normal at 9 months and another child who suffered from a relapse of proteinuria and hematuria at 6.5 months in CTX group.The results suggested that the efficacy of LEF and MMF was slightly better than CTX.During the observation period, all children were well tolerated and no serious adverse reactions occurred.One case showed a slight increase of alanine aminotransferase at 1 month, and returned to normal range at 3 months without any medication in MMF group.The cost of LEF group was(8 231±665)RMB and CTX group was(11 523±469)RMB which was significantly lower than(19 953±386)RMB in MMF group.Conclusion:LEF is as effective as MMF and CTX in the treatment of HSPN with nephrotic proteinuria in children.The adverse reactions of LEF are mild, and the cost is cheaper.LEF is worth popularizing in clinical practice.
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OBJECTIVE：To compare the effectiveness and safety of int ensified dose and standard dose of mycophenolic acids （MPA）for kidney transplant recipients ，and to provide evidence-based reference for clinical use of drugs. METHODS ：Retrieved from Embase ，PubMed，Cochrane library ，Clinical trials ，CNKI，Wanfang database and CBM ，randomized controlled trial （RCT） and cohort study about intensified dose and standard dose of clinical commonly used Mycophenotate mofetil （MMF） and Mycophenolate sodium enteric-coated tablet （EC-MPS）for adult kidney transplant recipients were collected during the inception to Mar. 2020. After literature screening and data extraction ，the quality of RCTs were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator manual 5.0. The quality of cohort study was evaluated by NOS scale. Meta-analysis was performed by using Rev Man 5.3 software，and sensitivity analysis was conducted. RESULTS ：A total of 8 studies were included，involving 6 RCTs，2 cohort studies ，with 1 637 patients involved. Meta-analysis results showed that ，the incidence of biopsy-proven acute rejection （BPAR）[RR＝0.65，95％CI（0.48，0.89），P＝0.007] and cytomegalovirus （CMV）infection [RR ＝ 0.39，95％CI（0.17，0.91），P＝0.03] in intensified dose groupwere significantly lower than control group. Subgroup analysis by drug showed that the incidence of BPAR in MMF intensive dose group [RR ＝0.72，95％CI（0.53，0.99），P＝0.04] and EC-MPS intensive dose group [RR ＝0.19，95％ CI （0.04， 0.81），P＝0.03] was significantly lower than that in standard zhaorongsheng@bjmu.edu.cn dose group ； there was n o statistical significance in the incidence of CMV infection in MMF intensive dose group [RR ＝0.16，95％CI（0.02，1.33），P＝0.09] and EC-MPS intensive dose group [RR ＝0.51，95％CI（0.20，1.30），P＝0.16]，compared with standard dose group （P＞0.05）. There was no significant difference in the incidence of rejection，treatment failure ，graft loss ，termination of treatment ，death，overall adverse events ， infection（overall），BK virus infection ，urinary tract infection ，hematological adverse events （overall），leucopenia，anemia， thrombocytopenia，gastrointestinal adverse events （overall），nausea，vomiting or diarrhea between 2 groups（P＞0.05）. Sensitivity analysis showed that the incidence of rejection ，CMV infection and leukopenia were generally stable. CONCLUSIONS ：The efficacy and safety of early intensive dose of MPA in adult renal transplant recipients were similar to those of standard dose ，but the incidence of rejection ，CMV infection and leucopenia should be carefully interpreted.
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Objective: The present study deals with the development, validation and application of a simple, precise and accurate HPLC method for the determination of mycophenolate mofetil in pharmaceutical formulations and microemulsions. Methods: In this method, a simple isocratic mobile phase composition of methanol and water (75:25 v/v) pumped at 1 ml/minute flow rate through Phenomenex C18 column (dimension: 250 4.6 mm and 5 µm particle size) was used. Injection volume was 20 µl and analysis of mycophenolate mofetil was carried out at 250 nm. Results: The coefficient of regression was found to be 0.9996, indicating the linearity of the developed method within a range of 0.1 to 10 µg/ml. The limit of detection (LOD) and the limit of quantization (LOQ) were found to be 3.660ng/ml and 11.091ng/ml, respectively. The results showed that % deviation for change in compositions of the mobile phase, flow rate and temperature was within a range of-5.51 to 10.99%,-3.70 to 8.80% and-5.29 to 10.90%, respectively. The method seemed sensitive to change of temperature (±5 ○C) and methanol composition (±2%) as the results were at the boundary limit of 10% deviation. Conclusion: A simple, precise and accurate HPLC method for the determination of drug content from microemulsion has been developed and validated in accordance with ICH guidelines.
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Introduction: Childhood nephrotic syndrome has an incidence of 90–100 per million population of India. This study was conducted with the primary objective of studying the prevalence of different clinical variants of childhood nephrotic syndrome (new-onset steroid-sensitive nephrotic syndrome/infrequent relapsing nephrotic syndrome [IFRNS]/frequently relapsing nephrotic syndrome [FRNS]/steroid-dependent nephrotic syndrome [SDNS]/steroid-resistant nephrotic syndrome [SRNS]), while the secondary objectives were to estimate the prevalence of use of steroid-sparing drugs in those with FRNS and SDNS. Materials and Methods: A retrospective study of all patients referred to renal diseases clinic at Government Medical College, Jammu, was done. Records of 61 children of 1–18 years of age fulfilling the International Study of Kidney Disease in Children criteria for nephrotic syndrome attending to our nephrology clinic were reviewed over 1 year period. Standard definitions for new-onset nephrotic syndrome, IFRNS, FRNS, SDNS, and SRNS were used. Steroid-sparing drugs used were levamisole in FRNS and low-dose SDNS whereas cyclophosphamide, mycophenolate mofetil (MMF), and tacrolimus in high-dose SDNS. Results: Among nephrotic syndrome, patients mean age of presentation was 5.95 years, with M: F ratio of 1.77:1. Infrequent relapsers (27.9%) were the most prevalent clinical variant followed by steroid-dependent nephrotic syndrome (24.6%) and new-onset nephrotic syndrome (21.3%). Prednisolone alone was successful in achieving remission in 50.8% of total cases and less commonly involving use of other immunosuppressants with prednisolone such as levamisole (23%), cyclophosphamide (9.8%), and tacrolimus in (3.3%). However, prednisolone in combination with cyclophosphamide and then MMF was used in 14 (23%) in an aim to achieve full remission, but full remission was achieved in 48 (78.7%). Conclusion: In the present study, clinical profile of children with nephrotic syndrome was concordant with typical nephrotic syndrome in children. Pattern of nephrotic syndrome differs in our population in terms of increased number with SDNS and response to treatment did not differ significantly from other studies.
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OBJECTIVES: Here, we aimed to compare the clinical effects of mycophenolate mofetil combined with either tacrolimus or with cyclophosphamide on lupus nephritis (LN) and to analyze their influence on the expression of cystatin C and on transforming growth factor-1 (TGF-β1). METHODS: A total of 234 patients were randomly divided into two groups: group A, for mycophenolate mofetil combined with tacrolimus (n=117) and group B, for mycophenolate mofetil combined with cyclophosphamide (n=117). The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum TGF-β1 and cystatin C before and after treatment. RESULTS: The total effectiveness rate in group A was much higher than that in group B. The times of effectiveness and effect validity in group A were much lower than those in group B. The expression levels of serum TGF-β1 and cystatin C decreased slightly after treatment in the two groups, and those of group A were much lower than those of group B. CONCLUSIONS: The combination of mycophenolate mofetil and tacrolimus showed better clinical efficacy on LN and was safer than that of mycophenolate mofetil and cyclophosphamide. Moreover, the drug combination of mycophenolate mofetil and tacrolimus greatly reduced the expression levels of serum TGF-β1 and cystatin C.
Subject(s)
Humans , Lupus Nephritis/drug therapy , Mycophenolic Acid/therapeutic use , Tacrolimus/therapeutic use , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Immunosuppressive Agents/therapeutic useABSTRACT
OBJECTIVE: To investigate the association of UGTs, ABCC2, SLCO1B1 and IMPDH gene polymorphisms with metabolism and adverse reaction of mycophenolate ester in early renal transplant recipients. METHODS: A total of 233 patients who received tacrolimus+glucocorticoid+mycophenolate mofetil treatment after living kidney transplantation were enrolled. Single nucleotide polymorphisms of 13 gene were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Kruskal-Wallis H test was used to analyze the effect of 13 single nucleotide polymorphisms on the exposure/dose (AUC/D) and adverse reactions of mycophenolic acid in early recipients after renal transplantation. RESULTS: The AUC/D of mycophenolic acid in UGT2B7 802C>T CC and CT genotype recipients was (36.03±16.19) and (38.06±15.41) mg•h•L-1/g•d-1, which was significantly lower than that in TT genotype recipients (43.63±15.10) mg•h•L-1/g•d-1 (P=0.021). The AUC/D of mycophenolic acid in SLCO1B1 521T > C TT, TC and CC genotype recipients were (36.78±15.70), (41.27±12.92) and (45.10±21.32) mg•h•L-1/g•d-1, respectively. There was significant difference between groups (P=0.036). There was no significant difference between 13 single nucleotide polymorphisms and adverse reactions (P>0.05). CONCLUSION: The AUC/D of mycophenolic acid in early recipients after kidney transplantation are associated with the polymorphism of UGT2B7 802C > T and SLCO1B1 521T > C.
ABSTRACT
Mycophenolic acid (MPA) drugs are common immunosuppressant for organ transplant recipients, which possesses high immunosuppressive effect. However, insufficient or excessive dosage of MPA is not conducive to clinical prognosis of the recipients. Hence, it is necessary to accurately control the dosage of MPA. The metabolism of MPA significantly differs among individuals. The metabolic pattern and monitoring method of these drugs are of important significance in clinic. In this article, the research progresses on the metabolism of MPA drugs in organ transplant recipients in recent five years were reviewed, the main results and direction of drug metabolism and monitoring methods were summarized, and the researches on the metabolism of MPA drugs in organ transplantation were briefly reviewed and prospected.
ABSTRACT
OBJECTIVE：To evaluate the cost-effectiveness between Mycophenolate mofetil （MMF）dispersible tablets versus MMF capsules for the immunosuppressive therapy after renal transplantation ，and to provide reference for selecting more economical MMF preparations. METHODS ：Based on a systematic review about MMF dispersible tablets and MMF capsules for immunosuppressive therapy after renal transplantation （involving 6 clinical studies ），with simulation period of 6 months，Treeage 2010 software was used to establish decision tree model ，which included four states of graft normal ，acute rejection ，graft loss and death. Using QALYs as effect measurement index ，the cost-effectiveness analysis of two MMF preparations was carried out in combination with the cost data of West China Hospital of Sichuan University. Signal factor sensitivity analysis and probability sensitivity analysis were performed . RESULTS ：The incremental cost-effectiveness ratio of MMF capsules group to MMF dispersible tablets group was 623 111.614 0 yuan/QALY，which was higher than Chinese willing-to-pay value （212 676 yuan/QALY）；the results of sensitivity analysis supported the above results. CONCLUSIONS ：MMF dispersible tablets are better than MMF capsules in cost-effectiveness of immunosuppressive therapy after renal transplantation.