Successful treatment of steroid-resistant minimal change disease with mycophenolate mofetil

Mycophenolate mofetil has been reported to be effective in the treatment of steroid-responsive minimal change disease. We report a case of steroid- and cyclosporin-resistant minimal change disease with severe nephrotic syndrome that responded to mycophenolate mofetil with complete remission. The patient remains in complete remission 1 year after the discontinuation of mycophenolate mofetil. The presented case argues for the need of a prospective controlled study with the goal of evaluating the efficacy of mycophenolate mofetil in the therapy of steroid-resistant minimal change disease.     

Successful steroid-sparing treatment of renal limited sarcoidosis with mycophenolate mofetil

Sarcoidosis is a multi-system disorder characterized by non-caseating epithelioid granulomas in multiple organs. The disease usually presents in young adults and is uncommon in children. Renal involvement can usually occur due to granulomatous interstitial nephritis, but renal failure is uncommon. Corticosteroids are the mainstay of therapy. We present the report of a child with severe renal failure secondary to renal limited sarcoidosis who was successfully treated with corticosteroid induction therapy. Because of the severe side effects of corticosteroids, mycophenolate mofetil was added and corticosteroids were tapered off. The child has been in sustained remission for over a year with mycophenolate mofetil monotherapy.     

他克莫司与霉酚酸酯治疗儿童难治性IgA肾病的疗效比较

目的比较他克莫司(tacrolimus,TAC)与霉酚酸酯(mycophenolate mofetil,MMF)在难治性IgA肾病(IgA nephropathy,IgAN)患儿的临床疗效。方法难治性IgAN的诊断定义为:在联合肾素-血管紧张素系统(RAS)阻断剂及糖皮质激素序贯治疗后,仍表现为大量蛋白尿(≥50 mg·kg-1·d-1)。遵循病例对照匹配方法,回顾性选取2012年1月1日至2016年12月31日在东部战区总医院行肾活检确诊为难治性IgAN的患儿76例,根据治疗方案将患儿分为TAC组(38例)和MMF组(38例),比较两组24 h尿蛋白量(24hUP)、血清白蛋白(Alb)、血清肌酐(Scr)、血清尿酸(UA)、血糖(Glu)、不良反应发生情况以及疗效等。结果两组患者间年龄、性别比、血压、估算肾小球滤过率(eGFR)、24hUP、尿红细胞计数(U-RBC)、Scr、Alb、BUN、天门冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、Glu及病理牛津分型、加用免疫抑制剂前行大剂量甲泼尼龙冲击治疗比例差异均无统计学意义(均P>0.05),两组患者具有可比性。用药3个月起,两组患儿24hUP均较基线值明显降低,差异有统计学意义(均P<0.05),且在3、6、12个月时TAC组24hUP均显著低于MMF组(均P<0.05)。TAC组Alb在用药1个月后即较基线值明显升高(P<0.05),而MMF组在用药3个月后明显升高(P<0.05),其中TAC组Alb在1、3、6个月时均高于MMF组(均P<0.05),在12个月时两组Alb差异无统计学意义。TAC组的总有效率、完全缓解率及无效率自用药3个月起与MMF组差异均有统计学意义(均P<0.05),但随访期间部分缓解率、随访时点复发率及累计复发率两组间差异无统计学意义(均P>0.05)。其中TAC组在6个月时达到最大有效率(94.7%),而MMF组在12个月时达到最大有效率(68.4%),差异有统计学意义(χ2=8.756,P=0.003)。两组不良反应发生率比较差异无统计学意义(15.8%比21.1%,χ2=0.350,P=0.554)。但TAC组在治疗3个月时血糖高于MMF组,差异有统计学意义[5.02(4.72,5.22)mmol/L比4.42(4.19,5.07)mmol/L,Z=-2.745,P=0.006]。结论TAC与MMF治疗难治性IgAN均取得良好的治疗效果,但TAC组更快达到缓解水平,且缓解率更高。     

Efficacy and safety of mycophenolate mofetil in treatment of IgA nephropathy: a systematic review

Objective To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in treatment of IgA nephropathy. Methods The Cochrane library, PubMed, EMBASE, Wanfang Data Knowledge Service Platform, CNKI and VIP were searched from the time when the databases were established to March 31, 2018. Reports on randomized controlled trials (RCTs) on treating IgAN with MMF were collected. Data were extracted and assessed independently by three reviewers and the methodological quality of included RCTs was assessed by the Cochrane collaboration's tool for assessing risk of bias. The Meta analysis of homogeneous RCTs was managed by using Stata 12.0. Results Nine RCTs, of which two RCTs were assessed as A-level studies scoring from 4 to 7 points, six RCTs were assessed as B-level studies scoring from 2 to 3 points, and one RCT was assessed as C-level study with scores less than 2 points, were enrolled in the study. Important outcomes of this systematic review were described as follows: (1) Compared to placebo plus ACEI/ARB or ACEI/ARB monotherapy, MMF plus ACEI/ARB did not reduce the incidence of increased serum creatinine and ESRD, but increased the partial remission rate of urinary protein (OR=2.59, 95%CI 1.01-6.65, P=0.049. (2) No significant difference was detected in the efficacy of reducing urinary protein for MMF monotherapy or MMF plus glucocorticoid (GC) compared to GC monotherapy. (3) MMF showed no significant difference in the efficacy of reducing urinary protein compared to LEF or CTX, but lower incidence rate of serum creatinine increasing than that of CTX group (OR=0.21, 95%CI 0.04-1.07, P=0.043. (4) Different levels of adverse reactions occurred in each treatment group with MMF, but most symptoms were mild, and recovered gradually after reducing or withdrawing MMF. Conclusions MMF monotherapy shows a superiority in curing IgAN compared to ACEI/ARB, but no significant superiority compared to GC. MMF can replace a part of the effect of GC when used in combination with GC and can reduce the dosage of GC compared to GC monotherapy. Additionally, MMF displays no better short-term efficacy than LEF or CTX, but a better long-term efficacy and fewer side effects than CTX. And the side effects occurred in the treatment groups with MMF are mostly mild, and disappear gradually after reducing or stopping the use of the drug. MMF is a safe and effective drug for the treatment of IgAN.     

Recurrent IgA nephropathy after renal transplantation despite immunosuppressive regimens with mycophenolate mofetil.

BACKGROUND: Transplantation offers an excellent option for patients with immunoglobulin-A nephropathy (IgAN) with severe renal dysfunction. However, IgAN frequently recurs in allografts treated with azathioprine. We examined the impact of mycophenolate mofetil immunosuppression on recurrence of IgAN. METHODS: We reviewed the charts of patients transplanted for IgAN at our institution in the cyclosporin era. Patients were excluded from further analysis if follow-up was <12 months or if immunosuppression at engraftment did not include azathioprine or mycophenolate mofetil. Laboratory data, medications and allograft biopsy findings were compiled. RESULTS: 152 kidney transplantations met the study criteria. At engraftment, 61 allografts were treated with azathioprine and 91 with mycophenolate mofetil. By 3 years post-transplant, IgAN developed in six of 60 (10.0%) azathioprine-treated allografts and five of 62 (8.1%) mycophenolate mofetil-treated allografts (P = 0.76). Overall, 13 azathioprine-treated and seven mycophenolate mofetil-treated allografts showed recurrence. As expected in this retrospective study, the duration of observation was longer in the azathioprine group. The interval between engraftment and diagnosis of recurrent disease was also longer. Survival of allografts with recurrent IgAN was similar in the two groups. Survival of allografts with recurrent IgAN was worse than for allografts without recurrence or allografts transplanted into patients with non-IgAN renal failure. Neither switching azathioprine to mycophenolate mofetil nor using an angiotensin-converting enzyme inhibitor or angiotensin-II type 1 receptor blocker ameliorated the clinical course after a biopsy documented recurrent IgAN. CONCLUSIONS: Mycophenolate mofetil, compared with azathioprine, did not lessen the recurrence of IgAN or its clinical impact.     

Therapy of IgA nephropathy with mycophenolate mofetil--report of 3 cases

Mycophenolate mofetil is an immunosuppressive agent in transplantation which inhibits the purin neogenesis. Proliferating lymphocytes are suppressed and antibody production is decreased. Many cases of successful therapy in different kidney diseases are reported, such as diffuse proliferative lupus nephritis, pauci-immune necrotizing glomerulonephritis, focal segmental glomerular sclerosis and IgA nephropathy. We report 3 patients with IgA nephropathy who were treated with mycophenolate mofetil for more than 1 year. In all patients, proteinuria decreased significantly and the renal function remained stable. In 2 patients, kidney biopsy was repeated after 12 months and 18 months, respectively. There were no histological signs of progression of the disease. Two patients developed infections during treatment. One patient had a pneumonia, and a second patient an infection with varizella zoster. Based on our data, mycophenolate mofetil can be a potential treatment of IgA nephropathy. Further controlled studys are warranted to investigate the role of mycophenolate mofetil in IgA nephropathy.     

Successful treatment of dialysis osteomalacia and dementia, using desferrioxamine infusions and oral 1-alpha hydroxycholecalciferol

A 54-year-old patient with fracturing dialysis osteomalacia and dementia demonstrated rapid deterioration following parathyroidectomy which was performed for sustained hypercalcemia. Reduction of the total body aluminum burden was attempted using desferrioxamine (DFO) as a chelating agent. After 6 months, DFO infusion resulted in sustained clinical remission of both neurological and skeletal symptoms, associated with an improvement in the EEG and improved mineralization of bone. A reduction in total body aluminum burden was reflected by reduced skeletal aluminum content, quantitated histochemically in iliac crest bone biopsies before and after DFO therapy. Dramatic increases in serum aluminum levels were documented in the initial weeks of DFO therapy leading to increased removal of aluminum during dialysis; in vitro studies indicated that the ultrafiltrable fraction of serum aluminum increased from 17 to more than 60% after initiating DFO treatment. However, after 6 months of therapy, serum aluminum levels remained unchanged after DFO infusion. These findings suggest that the serum aluminum response to DFO infusion might be a useful reflection of the total-body aluminum burden and also a reflection of the adequacy of a chelation program designed to reduce whole-body aluminum content.     

Successful treatment of postoperative chylothorax using an external pleuroperitoneal shunt.

We report 3 patients with chylothorax who were successfully managed as outpatients using external pleuroperitoneal shunts. This external shunt has the advantage over subcutaneously placed shunts of pumping large volumes of fluid with each compression of the pumping chamber, of not causing the discomfort associated with pumping a subcutaneous chamber, of not becoming difficult to find in the subcutaneous space, and of being constructed of larger components which do not kink or become easily clogged with fibrinous debris.     

霉酚酸酯联合激素治疗IgA肾病的疗效观察

本研究主要观察霉酚酸酯（MMF）联合激素对IgA肾病的临床疗效和安全性。 一、对象和方法 1．对象：病理确诊为IgA肾病，尿蛋白量（24h）≥1．0g，Scr〈265μmol／L，年龄14-70岁，1个月内未使用激素和免疫抑制剂的患者。排除标准：（1）既往曾对本药严重过敏；（2）白细胞〈3×10^9／L；（3）妊娠或可能妊娠；（4）Scr〉265μmol／L；（5）继发IgA肾病；（6）有肝功能损害。     

Successful treatment of Caroli''s disease by hepatic resection. Report of six patients.

Caroli's disease is a congenital disease of cystic or saccular dilatation of the intrahepatic bile ducts. There are two disease entities: a simple type and a periportal fibrosis type. Frequent complications with the simple type are recurrent cholangitis, liver abscess, intraductal lithiasis, abdominal pain, and fever that often lead to fatal sepsis. Development of portal hypertension and esophageal varices is usually a final feature of the periportal fibrosis type. Malignancies are also possible complications with Caroli's disease. During the recent 13 years, the author had experiences with eight patients with Caroli's disease of the simple type; six of these eight underwent hepatic resection: right lobectomy in two, left lobectomy in three, and left lateral segmentectomy in one. Other two patients died of sepsis and cholangiocellular carcinoma, respectively. All six patients with hepatic resections were relieved from the disabling symptoms after surgery and have had no recurrent hepatobiliary problems for 3 months to 13 years. Hepatic resection may be indicated for more patients than previously assumed in the treatment of Caroli's disease of the simple type.     

Successful treatment of proximal white subungual onychomycosis with oral terbinafine therapy

Proximal white subungual onychomycosis (PWSO) is a rare form of onychomycosis of both fingernails and toenails. It occurs when the fungus invades the stratum corneum of the proximal nailfold followed by infection of the deeper parts of the nail plate. The surface of the overlying nail is usually normal. A case of PWSO is described with complete cure by the use of oral terbinafine 250 mg/day for 3 months continuously.     

Successful treatment of chronic bone and joint infections with oral linezolid

Linezolid is an attractive alternative for the treatment of chronic bone and joint infections because it is active against common pathogens including methicillin-resistant staphylococci and vancomycin-resistant enterococci and because its oral formulation is convenient for long-term administration. To evaluate the ability of linezolid to produce long-term remission, we prospectively monitored 11 consecutive adult patients who received linezolid for osteomyelitis (n = 9) or prosthetic joint infection (n = 2). Linezolid 600 mg was administered orally twice daily for a mean of 10 weeks (range, 6 to 19 weeks). Pathogens were methicillin-resistant Staphylococcus aureus (n = 5), methicillin-resistant coagulase-negative staphylococci (n = 4), vancomycin-resistant Enterococcus faecium (n = 1), and vancomycin-sensitive Enterococcus faecalis (n = 1). After a mean followup of 27 months (range, 17 to 41 months), all 11 patients had remission by clinical, laboratory, and radiographic criteria. During week 8 of linezolid treatment, one patient developed a gram-negative superinfection, which resolved with appropriate therapy. During week 6 of linezolid treatment, one patient developed mild thrombocytopenia and another patient developed mild anemia. Both episodes of myelosuppression were reversible within 10 days after completing the planned 6-week courses of linezolid. We recommend weekly complete blood counts to detect hematologic abnormalities. We conclude that oral linezolid seems to be a useful and convenient alternative for the treatment of bone and joint infections.     

Successful treatment of combination therapy using an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker in a patient with IgA nephropathy

A 24-year-old Japanese woman with IgA nephropathy was admitted to our hospital due to the development of proteinuria and pretibial edema while on glucocorticoids and an angiotensin-converting-enzyme(ACE) inhibitor. She had been on both medications for more than 2 years. Urinary protein excretion was 2.53 g/day and renal function laboratory data were within the normal range. Plasma aldosterone concentration was high at 248 pg/ml, with normal plasma renin activity. The renal biopsy specimens showed prominent glomerular hypertrophy. Four weeks after the addition of valsartan, an angiotensin II receptor blocker(ARB), urinary protein excretion was remarkably reduced to 0.6 g/day without adversely affecting blood pressure. During the treatment period, proteinuria was maintained at less than 0.6 g/day and renal function remained normal. We propose that glomerular hypertension caused by insufficient suppression of the renin-angiotensin system was an essential factor underlying the increased urinary protein excretion in this patient. Combination therapy of an ARB and an ACE inhibitor appears to have a beneficial effect in patients with IgA nephropathy patients with persistent glomerular hypertension.