霉酚酸酯治疗难治性肾病综合征临床观察

原发性肾病综合征(NS)是临床上较为常见的一组肾小球疾病，对肾上腺糖皮质激素治疗无效或复发的NS目前缺乏有效的治疗方法。虽然环磷酰胺和环孢素A的介入可能取得部分疗效，但因其严重的不良反应而受到限制。1998年霉酚酸酯(MMF)被用于难治性肾病综合征的治疗并取得了较满意的疗效。我们总结了我院应用MMF治疗难治性     

霉酚酸酯治疗糖尿病肾病的研究进展

糖尿病肾病是糖尿病代谢异常引起的肾脏疾病,是全身微血管病的一部分,也是许多发展中国家终末期肾病的常见病因。近些年来,伴随着各项医疗技术的发展,有效控制了许多疾病,但是糖尿病肾病这种疾病仍旧尚未得到有效治疗,与其相关的发病率和死亡率有逐年上升的趋势。目前,相关研究发现,新型免疫抑制剂霉酚酸酯对糖尿病肾病具有一定的治疗作用。本文就新型免疫抑制剂霉酚酸酯对糖尿病肾病治疗的研究进展作一综述。     

霉酚酸酯治疗难治性肾病15例

难治性肾病是原发性肾病综合征中频繁复发、激素依赖、激素耐药病例的总称 ,临床治疗较为棘手 ,严重影响患儿的生命质量。 1998年 ,国外即开始使用霉酚酸酯 (商品名 :骁悉 )治疗肾小球疾病[1] ,我们于 2 0 0 0年开始试用霉酚酸酯治疗难治性肾病 ,并取得了满意疗效 ,现报告如下。1　资料与方法1.1　病例选择　 15例患儿均为 2 0 0 0年 6月至 2 0 0 2年 3月间住院的难治性肾病患儿。年龄 3～ 12岁 ,平均 6.5岁 ;病程2月至 3年 ,平均 13个月。所有患儿治疗前的血白细胞均大于 4× 10 9/Ｌ ,肝功能检查未见异常。其中频繁复发 3例 ,激素依赖 5例…     

霉酚酸酯治疗难治性肾病综合征

原发性肾病综合征是常见的肾小球疾病,是由不同疾病组成的临床症候群,降低和阴转尿蛋白、保护肾功能为其主要治疗目标,基本治疗方案为抑制免疫及其介质的炎症反应,常见药物有糖皮质激素、环磷酰胺、苯丁酸氮芥等。对于应用皮质激素有效的病理类型,如微小病变肾病和系膜增生性肾小球肾炎,可根据对皮质激素的反应,分为激素敏感型、激素依赖型和激素抵抗型。后两者和对激素效果相对差的病理类型如膜性肾病(MN)、局灶节段硬化(FSGS)和膜增殖性肾小球肾炎(MPGN)可称为难治性肾病综合征。目前对于难治性肾病综合征的治疗缺乏有效的方法。     

霉酚酸酯治疗IgA肾病疗效观察

目的:研究麦考酚酸酯(MMF)对IgA肾病的临床疗效、安全性和耐受性。方法:蛋白尿>2.0g/d,血肌酐<355μmol/L的IgA肾病患者,均经肾活检证实病理为重度系膜增生性肾炎、局灶节段性肾小球硬化、系膜毛细血管性肾炎,采用激素联合MMF(1.0～1.5g/d)治疗,随访12个月,观察24h尿蛋白定量、血浆尿素氮、肌酐、白蛋白、甘油三酯、胆固醇及肝功能等多项临床指标。结果:18例患者中13例尿蛋白、尿红细胞获得完全缓解,3例为部分缓解,其中1例肾功能轻度损害,治疗后恢复正常。结论:MMF对病理改变较重的IgA肾病近期有较好疗效,未见明显毒副作用,耐受性好。     

霉酚酸酯循证治疗特发性膜性肾病合并肾病综合征1例报告

目的报告1例特发性膜性肾病(IMN)合并肾病综合征(NS)患者应用霉酚酸酯进行循证治疗的结果。方法计算机检索Cochrane(2005年第3期)、MEDLINE(1978～2006)和CNKI(1978～2006),查找霉酚酸酯治疗IMN合并NS及与病情缓解有关的系统评价、临床随机对照试验、队列研究和病例对照研究等,并对所获证据进行质量评价,进而应用于本例患者的临床治疗。结果现有C级临床证据表明,霉酚酸酯能提高IMN合并NS患者的蛋白尿缓解率,对激素或烷化剂耐药的患者也有一定疗效,但能否提高肾脏的长期存活率尚无可靠证据。据此,结合医生经验及患者意愿,对患者采取霉酚酸酯联合糖皮质激素治疗,按患者体重(50kg)使用霉酚酸酯2．0g／d和强的松25 mg/d,并同时给予活血化瘀及对症支持治疗,3月后患者蛋白尿有所缓解。目前仍在随访中。结论现有C级证据表明短期内霉酚酸酯能提高IMN合并NS患者的蛋白尿缓解率,但能否提高患者肾脏长期存活率以及卫生经济学评价有待进一步研究。     

肾病综合征并发脑梗塞1例并文献复习

肾病综合征（nephrotic syndrome,NS）是临床常见的综合症候群.血栓形成是其并发症之一,国外报道发生率为20%[1],最常见于静脉血栓形成,其中肾静脉血栓形成发病率最高[2],脑血栓形成少见.     

肾病综合征并类固醇糖尿病3例

我院1993年5月～1994年5月收治接受激素治疗的肾病综合征患者11例,男7例,女4例;年龄大于40岁5例,青少年6例。治疗过程中出现糖尿病3例,     

霉酚酸酯治疗难治性肾病综合征的临床探讨

难治性肾病综合征在临床治疗中非常棘手,我院运用霉酚酸酯(MMF)治疗难治性肾病综合征,临床观察有一定疗效,现总结如下。     

Schmidt's syndrome in a child with diabetes mellitus

Schmidt's syndrome (thyroid and adrenal insufficiency) and concurrent diabetes mellitus represent an intriguing multiple endocrinopathy in children. This report describes an eleven-year-old girl with diabetes of eight years' duration presenting in adrenal crisis. Serum thyroxine was undetectable, and antibodies to both thyroglobulin and adrenal tissue were found in high titer. The child's condition stabilized with hormonal replacement therapy, except for persistent growth failure. Approximately two years later she succumbed during a rapidly fulminant episode of ketoacidosis. The natural history of her illness supports recent speculation based on serologic data that juvenile diabetes mellitus may be an immunologic disorder in some children.     

Effective therapy of a child case of refractory nephrotic syndrome with tacrolimus

We report here the case of a 9-year-old Japanese boy with nephrotic syndrome caused by focal segmental glomerulosclerosis, which was refractory to treatment. Although aggressive immunosuppressive therapy consisting of methylprednisolone pulse therapy combined with cyclosporine A (CsA) and intermittent low density lipoprotein apheresis was effective in overcoming his steroid-resistant state, the child became persistently steroid-dependent, that is, more than 0.75 mg/kg per day of prednisolone combined with CsA was required to maintain a negative test for proteinuria. Since adverse effects of prednisolone, such as short stature, obesity, osteoporosis and cataract, were noted, CsA in his treatment regimen was replaced with tacrolimus at the dose of 0.1 mg/kg per day, with the trough blood level of the drug maintained at around 10 ng/ml. Within 4 months of the inclusion of tacrolimus in the treatment regimen, complete remission was achieved, with no recurrence of the proteinuria, while the prednisolone dose could be tapered to 0.3 mg/kg per day. No adverse effects of tacrolimus were observed. These clinical results suggest that tacrolimus may be the drug of choice in selected patients with refractory nephrotic syndrome, even if pediatric-onset cases, at least those in whom the steroid-sparing effects of CsA is unsatisfactory.     

儿童迟发型鸟氨酸氨甲酰基转移酶缺乏症三例分析并文献复习

目的总结鸟氨酸氨甲酰基转移酶缺乏症(OTCD)临床特点、诊治经验,提高对此病的认识。方法回顾性分析2013~2015年重庆医科大学附属儿童医院确诊的3例OTCD患儿临床诊治经过及实验室检查,并结合国内外资料进行文献复习。结果 (1)1例患儿为男性,2例患儿为女性,起病年龄均>1岁;2例有高蛋白饮食诱因;均无家族史;(2)1例以消化道症状起病,逐渐出现神经系统症状,病情进展迅速而死亡;2例以神经、精神症状为首发主要表现,经药物治疗后血氨降低,定期随访中;(3)3例患儿均有明显高氨血症,尿气相色谱均提示尿嘧啶升高;鸟氨酸氨甲酰基转移酶基因均有突变,突变位点各异;(4)治疗包括积极对症治疗及降血氨治疗。结论 OTCD以高氨血症引起的神经系统功能障碍为主要表现,临床表现各异,确诊可通过基因检测。     

Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an effective posttransplantation immunosuppressive agent used in combination with cyclosporin A (CsA) or tacrolimus (Tc). An increase in plasma mycophenolic acid (MPA) has been shown in patients receiving Tc-MMF combination therapy compared with CsA-MMF combination therapy at the same dose of MMF. The aim of this prospective study was to assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship for MPA in kidney transplant patients receiving low-dose MMF (500 mg twice a day) in combination with Tc. METHODS: Adult kidney transplant recipients (n = 51) were included. MPA-PK profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained within the first 2 weeks after transplantation, 3 months after grafting, and at every adverse clinical event [side effect or acute rejection (AR)]. All patients received Tc, MMF (500 mg twice a day), and steroids. RESULTS: Thirty patients (59%) had uneventful outcomes, and 21 patients had 33 episodes of MPA-related side effects; only 3 patients had AR. A total of 78 MPA-PK profiles were obtained. The following PK parameters were increased in the side-effects group compared with the non-side effects group: mean MPA c(min), 2.63 +/- 1.58 vs 1.75 +/- 0.82 mg/L (P = 0.016); mean c(30), 10.47 +/- 6.27 vs 7.66 +/- 8.95 mg/L (P = 0.009); mean c(60), 9.67 +/- 5.42 vs 5.83 +/- 2.6 mg/L (P = 0.0002); mean area under the MPA time-concentration curve from 0 to 12 h [MPA-AUC((0-12))], 48.38 +/- 18.5 vs 36.04 +/- 10.82 mg. h/L (P = 0.0006); mean dose-normalized MPA-AUC, 0.16 +/- 0.05 vs 0.12 +/- 0.04 (mg. h/L)/(mg/m(2)) (P = 0.0015). For the three AR patients, MPA concentrations obtained at the time of AR revealed MPA c(min) values of 1.86, 1.76, and 3.83 mg/L, respectively, and MPA-AUC((0-12)) values of 37.7, 24.9, and 104.9 mg. h/L. The threshold of toxicity was 3 mg/L (sensitivity, 38.7%; specificity, 91.5%) for c(min), 8.09 mg/L for maximum MPA concentration during the first hour (sensitivity, 77.8%; specificity, 67.4%), and 37.6 mg. h/L for MPA-AUC((0-12)) (sensitivity, 83.3%; specificity, 59.6%). CONCLUSIONS: These results demonstrate the relationship between plasma MPA concentrations and toxicity. High c(min), c(30), and c(60) values as well as AUC((0-12)) are associated with increased risk for side effects. These values may have an importance in a routine monitoring program.     

A comparison of a standard-dose prednisone regimen and mycophenolate mofetil combined with a lower prednisone dose in chinese adults with idiopathic nephrotic syndrome who were carriers of hepatitis B surface antigen: A prospective cohort study

Background: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV.Objective: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV.Methods: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV. Patients were self-assigned to 1 of 2 treatment groups: the standard prednisone regimen of 1 mg/kg daily or oral MMF 0.5 to 1.0 g BID combined with the lower pred-nisone dose of 0.5 mg/kg daily. The planned duration of treatment was 36 weeks, with an additional 60 weeks of follow-up. The primary outcome measures were rates of complete remission of idiopathic nephrotic syndrome (a decrease in daily proteinuria to within the normal range [<0.3 g]) and rates of HBV reactivation (detectable serum HBV DNA). Secondary outcome measures included relapse rates (>1+ albuminuria on dipstick urinalysis on 3 consecutive days), alanine ami-notransferase (ALT) elevations (>50 U/L), use of la-mivudine 100 mg/d (added if HBV DNA titers reached ≥10⁵ copies/mL), and adverse effects.Results: The intent-to-treat population included 41 patients (22 prednisone, 19 MMF). In patients who completed the study, rates of complete remission after 24 weeks of treatment were 78.9% (15/19) in the prednisone group and 76.5% (13/17) in the MMF group; 2 and 3 patients in the respective groups had a partial remission, and 2 and 1 patient had no response. HBV reactivation occurred in 63.6% (14/22) and 36.8% (7/19) of patients (P = 0.047). The only significant difference in the study was in the probability of HBV reactivation between groups (P = 0.043, log-rank test). During follow-up, at least 1 relapse occurred in 46.7% (7/15) and 30.8% (4/13) of patients. Elevations in ALT were observed in 36.4% (8/22) and 26.3% (5/19) of patients, and the addition of lamivu-dine was required in 40.9% (9/22) and 21.1% (4/19) of patients. The most frequent adverse effects in both groups were infections (27.3% and 26.3%), followed by gastrointestinal symptoms (13.6% and 21.1%). Two MMF patients developed leukopenia. One patient in the prednisone group discontinued treatment because of severe hepatitis, and 1 patient in the MMF group discontinued because of severe pulmonary infection.Conclusions: Among the adult Chinese patients with MSNS-HBV who completed this study, there were no significant differences in remission rates of idiopathic nephrotic syndrome between the standard prednisone regimen and the combination of MMF and a reduced prednisone dose. Rates of HBV reactivation, however, were significantly lower in the combination-therapy group.     

Monitoring trough plasma concentrations of mycophenolate mofetil in patients with uveitis

BACKGROUND: Mycophenolate mofetil (MMF) has been used successfully in patients with various forms of uveitis not responsive to other immunosuppressants. Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available. OBJECTIVE: To describe the results of the therapeutic drug monitoring (TDM) of MMF trough concentrations in a cohort of patients with uveitis, with the aim of optimizing the dosage of this drug, by maintaining a target concentration to achieve adequate immunosuppression with a minimal risk of therapeutic failure or toxicity. PATIENTS AND METHODS: This study describes the results of monitoring trough plasma concentrations of MMF in 12 patients with uveitis during a mean period of 21.4 months. Patients included one with Stevens-Johnson syndrome, one with Graves-Basedow's disease, one with Behcet's disease, one with idiopathic thrombocytopenic purpura and the rest with idiopathic uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF. RESULTS: Pharmacokinetic monitoring of mycophenolic acid (MPA) was performed with 108 trough plasma samples using an EMIT assay. Mean daily MMF dose was 24.5 +/- 6.3 mg/kg and mean trough MPA concentration was 2.9 +/- 1.9 microg/mL. Therapy was effective in 10 patients (83%). There were few side-effects: diarrhoea, excitement, agitation and cough that disappeared with daily dose reduction of MMF. CONCLUSIONS: MMF was effective in the majority of patients with uveitis with an acceptable profile of side-effects. TDM of MMF in patients with uveitis is clinically practicable and may help to optimize individual immunosuppressive therapy. We estimated that MMF dosages in the range of 0.5-1.5 g/day might be sufficient for treating uveitis and we recommend an initial target range of 2-4 microg/mL, which included 50% of our results. Randomized controlled trials are essential to confirm the efficacy of MMF in uveitis.