Disseminated bartonellosis in a child with steroid-dependent nephrotic syndrome receiving mycophenolate mofetil monotherapy

Cat scratch disease, usually a benign infectious disease, may develop as multisystem disease with multiorgan involvement, particularly in immunocompromised patients. We report on a patient who developed disseminated bartonellosis while receiving mycophenolate mofetil monotherapy treating steroid-dependent nephrotic syndrome, highlighting that severe infection can be observed in those patients. Therefore, this category of patients should be cautious when having contact with kittens and receives proper prevention advice.     

Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil

Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot ⁵¹Cr-EDTA clearance) showed a decline from 131±21 ml/min per 1.73 m² to 116±27 ml/min per 1.73 m² at last follow-up. Similarly, effective renal plasma flow (simultaneous ¹²³I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980±318 ml/min per 1.73 m² to 724±242 ml/min per 1.73 m². In a pilot study we investigated the effect of mycofenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.     

Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions

Clinicians are often faced with therapeutic dilemmas and challenges while treating children with frequently relapsing steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children with SDNS have been treated with long-term alternate day steroids cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine. The essential aim of these therapies is to maintain remission while limiting exposure to steroids. These medications have variable efficacy and undesirable toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new therapeutic option for the management of SDNS in a few uncontrolled clinical trials. Preliminary data are encouraging. MMF was found to be useful in maintaining remission and has a steroid-sparing effect. Clearly, more data are needed to further characterize the safety and efficacy of MMF, define adequate length of treatment, and optimize drug exposure and monitoring. The management of SRNS is primarily aimed at decreasing proteinuria and inducing remission, if possible. By doing so, one would aim to preserve renal function. CSA therapy is known to be useful in this regard but has undesirable side effects, the most concerning being nephrotoxicity. MMF in combination with steroids and angiotensin-converting enzyme-inhibitor drugs is known to have some efficacy in the management of SRNS. These preliminary data have prompted the National Institutes of Health to sponsor a multicentric controlled trial to compare the safety and efficacy of MMF with that of CSA in the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious, it would help obviate the need for CSA and its associated nephrotoxicity. Clearly, MMF has emerged as an important new therapeutic option for the treatment of childhood nephrotic syndrome and FSGS. Further data are required to assess those conditions most likely to respond.     

A prospective study on the use of mycophenolate mofetil in children with cyclosporine-dependent nephrotic syndrome

Cyclosporine A (CsA) has relieved children with steroid-dependent nephrotic syndrome (NS) from steroid toxicity. However, most patients frequently relapse again when CsA is withdrawn, resulting in the development of CsA nephropathy for its long-term use. In order to assess the efficacy of mycophenolate mofetil (MMF) therapy, we prospectively analyzed 12 children with idiopathic steroid-dependent NS requiring long-term CsA therapy with MMF for at least 6 months. Mean follow-up after starting MMF was 11 months (range 6–42). The mean MMF dose required was 610±95 mg/m²/12 h, which maintained mean predose mycophenolic acid (C0-MPA) levels of 2.4±1.1 mcg/ml. Treatment with MMF resulted in CsA and/or prednisolone (PSL) sparing, with a reduction in mean CsA dose from 3.5±1.3 to 1.5±2.4 mg/kg/day (p<0.01), and mean PSL dose from 0.29±0.16 to 0.21±0.11 mg/kg/day (p<0.05). Nine of 12 patients (75%) were finally able to be weaned off CsA. Mean relapse rates decreased from 2.7±1.6 to 0.6±0.9 episodes/year (p<0.01). Relapse-free ratio on MMF therapy was lower in patients whose average C0-MPA levels were less than 2 mcg/ml (p<0.05). Our experience demonstrates that MMF therapy results in significant CsA and/or steroid sparing and reduction in relapse rates in children with CsA-dependent NS.     

Experience with levamisole in frequently relapsing, steroid-dependent nephrotic syndrome

This was a controlled prospective study on the use of an immunomodulator drug, levamisole, in the treatment of frequently relapsing, steroid-dependent (FR/SD) idiopathic nephrotic syndrome. The study was started on 1 January 2001 and completed on 31 December 2003. There were two groups: a treatment group who received levamisole (2.5 mg/kg) on alternate days for 1 year and a control group who received low-dose prednisolone only (<0.5 mg/kg) on alternate days for 1 year. There were a total of 56 patients (32 in the treatment group and 24 in the control group). The male to female ratio was 1.66:1 in both groups. The mean age upon initial diagnosis was 3.3 years in the levamisole group versus 4.3 years in the control group. The mean duration from diagnosis to the start of the second line treatment was 3.2 years in the levamisole group versus 2.8 years in the control group. The relapse rate and the total cumulative dose of prednisolone during the year prior to second line therapy was compared to that during the year following the institution of second line therapy in 56 patients. The mean relapse rate was reduced more significantly in the levamisole group. It was reduced by 0.29 versus 0.11 relapses/patient/month in the control group (P =0.0001). The mean cumulative dose of steroids was also reduced more significantly in the levamisole group. It was reduced by 293 versus 102 mg/m²/month in the control group (P <0.0001). Therapy failure was seen in 3/32 (9.4%) in the levamisole group versus 12/24 (50%) in the control group. Of the patients, 20/32 (62.5%) using levamisole were relapse-free in the follow-up year post therapy, while no patient was relapse-free in the control group over the same period. No major adverse effects of levamisole were seen. The cost of levamisole therapy was estimated to be US$ 25 per year for a 20-kg body weight child. Thus, we concluded that levamisole is a highly efficacious, safe and easily affordable initial therapy for FR/SD idiopathic nephrotic syndrome.     

Switch from cyclosporine A to mycophenolate mofetil in nephrotic children

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3–15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (C_IN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m² twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m² per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26–2.94] mg/kg/d pre-MMF to 0.29 [0–1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.     

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m² per day (n = 12) or CsA 4–5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.     

Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil

We report a 21-year-old male with childhood-onset familial nephrotic syndrome and frequent relapses who manifested toxicity or treatment resistance to corticosteroids, cyclophosphamide, cyclosporin-A, and tacrolimus. Monotherapy with mycophenolate mofetil (MMF) resulted in maintenance of clinical remission for 14 months without noticeable toxicity, while allowing resolution of steroid-induced side effects. Our observation suggests that MMF may be useful in maintaining remission in nephrotic patients who manifest toxicity to standard immunosuppressive agents. Received: 6 April 1999 / Revised: 10 August 1999 / Accepted: 13 August 1999     

Pulse cyclophosphamide therapy in steroid-dependent nephrotic syndrome

Intravenous cyclophosphamide (IVCP) has been shown to be effective in lupus nephritis. This is a randomized controlled trial to compare the effectiveness of IVCP with oral cyclophosphamide (OCP) in patients with steroid-dependent (SD) idiopathic nephrotic syndrome (INS). Forty-seven consecutive children who were SD were randomized to receive either OCP (2 mg/kg per day×12 weeks) or IVCP (500 mg/m² per month IV×6 months) after achieving a steroid-induced remission. The response was evaluated in terms of remission, change in steroid response status, duration of remission (i.e., proteinuria-free days), side effects, and compliance. Of the 47, IVCP was given to 26 children and OCP to 21 children. The demographic data, histopathology, biochemical profile, and duration of follow-up in the two groups were similar. On Kaplan-Meier survival analysis, the median proteinura-free time was 360±88 days compared with 96±88 days in the OCP group (values median±SE, log rank P=0.05). The actuarial cumulative sustained remission in our study was 73% in IVCP compared with 38.1% in OCP at 6 months after therapy, but was almost identical (18.6% in IVCP vs. 19%in OCP) after 2 years. Thus in our study the overall improvement in steroid response category from SD to sustained remission, infrequent relapser, and frequent relapser (88% in IVCP vs. 57% in OCP) was significantly better in the IVCP group, although the number of children with persistent remission tended to be similar at 2 years. Furthermore, the response was observed with a 40% lower cumulative dose than OCP. Hence, we conclude that IVCP is a safe and effective therapeutic modality in children with INS who are SD.     

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2–12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5–17) with an initial dose of 600 mg/m²/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5–5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m²/12 h (range 415–970), which maintained mean C₀-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2–5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.     

Maintenance therapy with mycophenolate mofetil after rituximab in pediatric patients with steroid-dependent nephrotic syndrome

Rituximab (RTX) has a significant steroid-sparing effect in children with steroid-dependent nephrotic syndrome (SDNS). However, patients are likely to relapse with the recovery of CD20+ cells. We conducted a small prospective cohort study with a historical control to evaluate the effect of RTX infusion followed by mycophenolate mofetil (MMF) as a maintenance therapy. Nine patients with SDNS who stopped their steroid treatment but were treated with MMF after RTX infusion were prospectively observed (group A). Seven patients with SDNS who discontinued steroid and immunosuppressive agents after RTX administration served as a control (group B). During the first year after the administration of RTX, six patients in group A and one patient in group B did not suffer a relapse (p < 0.05). The number of patients who relapsed during the 1 year preceding RTX treatment did not differ between the two groups [4.1 (A) vs. 5.7 (B)], but it was significantly lower in the MMF-treated group 1 year after the RTX treatment [0.4 (A) vs. 2.3 (B), p < 0.005]. The daily amount of prednisolone after the RTX treatment was lower in group A than in group B (0.11 vs. 0.46 mg/kg/day, respectively; p < 0.05). Three patients in group A and five patients in group B relapsed to SDNS and needed additional RTX treatment(s) within 1 year (odds ratio 5.0). Based on these results, we conclude that maintenance therapy with MMF after RTX is a good clinical option.     

吗替麦考酚酯治疗原发性肾病综合征的前瞻性多中心临床研究

目的观察吗替麦考酚酯(MMF)联合激素治疗原发性肾病综合征(PNS)的疗效及安全性。方法采用前瞻性多中心方法,9个中心共47例患者入选。其中初治患者16例,难治性患者31例。用MMF联合激素治疗。MMF起始剂量为1.0～2.0g/d,至少3个月后开始减量,至12个月时维持在0.75～1.0g/d。口服泼尼松起始剂量0.8～1.0mg·kg-1·d-1,根据疗效减量,至6个月时至少减至传统治疗剂量的50%或以下。定期监测蛋白尿等生化指标及副作用。随访期≥6个月。结果47例患者蛋白尿水平从治疗后第2周起明显下降,由治疗前(6.46±3.18)g/d降至治疗后6个月时的(1.45±2.47)g/d(P<0.01),31/47例达到缓解;治疗后12个月时为(0.96±4.17)g/d(P<0.01),23/26例达到缓解。平均缓解时间为(10.89±11.49)周。初治组与难治性NS组均有效(P<0.01),组间差异无显著性意义(P>0.05)。治疗前后Scr无明显改变(P>0.05),血清白蛋白显著上升(P<0.01),血胆固醇水平明显下降(P<0.05)。微小病变组中6个月时有6/8例已达缓解,治疗后12个月时有4/4例仍处于缓解。系膜增生性肾小球肾炎组中治疗后6个月时有8/10例已达缓解,治疗后12个月时有6/7例仍处于缓解。膜性肾病组中治疗后6个月时有4/10例已达缓解,治疗后12个月时有2/4例仍处于缓解。局灶节段性肾小球硬化组中治疗后6个     

Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome

Development of steroid dependency represents a significant therapeutic challenge in steroid-sensitive nephrotic syndrome. Previous studies have shown conflicting results concerning the benefit of a 12-week treatment with cyclophosphamide (CPO), with 24%–67% of patients achieving long-term remission. We therefore analyzed the clinical response of 20 consecutive children with steroid-dependent nephrotic syndrome (SDNS) (12 male, median age at start of treatment 5.9 years, range 3.2–14.7 years) treated at our institution with CPO (2 mg/kg per day) for 12 weeks since 1989. Median duration of follow-up was 5.8 (range 1.1–9.25) years. Only 6 of 20 children (30%) showed a long-term remission of >2 years, while 14 of 20 (70%) developed relapses again. Of these, 12 patients (86%) again developed steroid dependency, requiring further alternative treatment. Our data show that a 12-week course of CPO leads to unfavorable results in the majority of patients with SDNS. We therefore conclude that there is a need for further optimization of therapy in SDNS. Received: 16 August 1999 / Revised: 21 October 1999 / Accepted: 25 October 1999     

Clinical observations of mycophenolate mofetil therapy in refractory primary nephrotic syndrome

SUMMARY:   Mycophenolate mofetil (MMF) is an effective immunosuppressive agent in renal transplantation, and preliminary studies suggest that it may also be effective in the treatment of lupus nephritis. This study investigated the efficacy and safety of MMF therapy in patients with refractory primary nephrotic syndrome in a prospective multicentre clinical observation. Nineteen refractory nephrotic patients with minimal change disease or mesangial proliferative glomerulonephritis were enrolled in this study. Combined MMF and prednisone therapy was used for 6 months with an initial MMF dose of 1.0–2.0 g/day and a prednisone dose of 20–60 mg/day; both drugs were tapered gradually. It was found that all patients achieved clinical remission and 11 of 19 responded within 4 weeks, and 12 of 19 patients entered complete clinical remission. The prednisone dose in those patients who were previously steroid dependent could be successfully tapered. During follow up, three patients experienced transient increasing of proteinuria associated with infections and recovered without an adjustment of therapy. One patient was withdrawn from the study because of a fall in haemoglobin levels; other adverse effects did not necessitate withdrawal. Follow-up renal biopsies in two patients found no alteration in renal pathology. Mycophenolate mofetil is an effective and well-tolerated immunosuppressive agent for patients with refractory nephrotic syndrome.     

吗替麦考酚酯联合低剂量激素治疗HBsAg阳性的成人微小病变性肾病综合征

目的 探讨吗替麦考酚酯（MMF）联合低剂量糖皮质激素方案治疗HBsAg阳性的成人微小病变性肾病综合征的疗效及安全性。 方法 前瞻性地选择HBsAg阳性、HBeAg 阴性及血清 HBV-DNA <1000 拷贝/ml的成人微小病变性肾病综合征患者30例,分成激素组（16例）及MMF组（14例）。激素组接受常规激素治疗方案（泼尼松片,1 mg&#8226;kg-1&#8226;d-1）;MMF组接受低剂量激素（泼尼松片,0.5 mg&#8226;kg-1&#8226;d-1）联合MMF 1.0~2.0 g/d。 结果 激素组和MMF组乙肝病毒激活发生比例分别为62.5%及35.7%,其中接受拉米呋定治疗分别为43.8%及21.4%;谷丙转氨酶升高发生比例分别为50.0%及28.6%。激素组及MMF组的完全缓解比例分别为11/14和10/12,两组复发比例分别为6/11和4/10。 结论 与常规激素治疗方案比较,MMF联合低剂量糖皮质激素方案能同样有效地治疗HBsAg阳性的成人微小病变性肾病综合征,并在减少乙肝病毒激活方面可能显示一定优势     

Vincristine treatment in steroid-dependent nephrotic syndrome

Treatment of children with steroid-dependent nephrotic syndrome (SDNS) continues to be a challenge when relapses recur after treatment with cyclophosphamide and side effects or non-compliance make steroids and cyclosporin unsatisfactory. We treated 12 patients with intravenous vincristine for SDNS in a regime of 1–1.5 mg/m² weekly for 4 weeks then monthly for 4 months. Four of the 5 patients in relapse when commencing vincristine remitted within 2 doses. Comparing relapse frequency in the 12 months before and after vincristine, there was a reduction from 4 to 1.5 (p=0.004) relapses per year. Median sustained remission was 5 months, but 1 frequently relapsing patient remains in remission 4 years after vincristine. Vincristine was also successfully used in 1 or 2 doses at weekly intervals for subsequent relapses in 5 patients. Side effects were minimal in most cases. Abdominal pain occurred in 2 patients who commenced vincristine at 1.5 mg/m², but resolved when continued at 1 mg/m². We felt vincristine had a role in a subset of children with challenging SDNS administered as 1 mg/m² weekly for 4 weeks then 1.5 mg/m² monthly for 4 months. Vincristine allowed steroid- and cyclosporin-sparing, contributed to long-term remission in some patients, and was especially valuable in children with poor compliance with oral medication. Many patients expressed a preference for a few doses of vincristine rather than a standard course of oral prednisolone or cyclosporin.     

Outcome of severe steroid-dependent nephrotic syndrome treated with mycophenolate mofetil

Background

Mycophenolate mofetil (MMF) is used as a steroid-sparing agent in pediatric nephrotic syndrome (NS). However, data about its long-term efficacy and safety is limited.

Methods

We report the long-term outcome of MMF therapy in 46 NS patients who remained steroid dependent (SD) despite previous treatment with levamisole and cyclophosphamide.

Results

After 1?year of MMF initiation, 32 (70?%) patients had reduced steroid requirement: 12 with decreased threshold dose and 20 were able to stop steroids. At follow-up of mean 3.56 (standard deviation?+?1.76) years, 25 (54?%) children required no further alternative immunosuppression (IS), having infrequent or no relapses, of which 14 stopped MMF after a mean 2.4 (standard deviation?+?0.9) years; 11 are continuing on MMF for a median of 2.25?years (range 1.33?C7.75?years). One patient had a psoriasis flare, and MMF was stopped. No other patient required permanent drug withdrawal due to side effects. The outcome of patients who did not require further alternate IS was significantly better than those who did, with 56?% vs. 10.5?%, respectively, being off regular medications at last follow-up.

Conclusions

We conclude that MMF therapy is safe in the long term and allows >50?% of severe SDNS patients to avoid further toxic IS.     

Rituximab therapy for steroid-dependent minimal change nephrotic syndrome

We present a patient with steroid-sensitive but high-dose steroid-dependent nephrotic syndrome who was treated with rituximab. For 9 months following therapy she had undetectable CD19 cells in the peripheral circulation. She remained in remission during this period even though therapy was reduced to low-dose, alternate day prednisolone only. After 9 months, CD19 cells were once again detectable. Shortly after CD19 cells became detectable again she relapsed. We conclude that B-lymphocytes play a central role in the pathogenesis of idiopathic minimal change nephrotic syndrome (MCNS) and that rituximab may have a useful role in the management of steroid-dependent patients.     

Villous atrophy induced by mycophenolate mofetil in renal-transplant patients

Leucopenia and diarrhoea are the main side effects observed after the use of mycophenolate mofetil (MMF) in renal-transplant patients. The mechanism of diarrhoea remains unknown. We report on four cases presenting with severe diarrhoea, which appeared, respectively, at 4, 10, 24, and 66 months after MMF therapy had been started. All patients presented with weight loss and biological signs of malabsorption syndrome. Oesophago-gastroduodenoscopy revealed duodenal villous atrophy, which was confirmed by pathology examination. Anti-endomysium antibodies were negative. In all patients, diarrhoea disappeared within 1 month of MMF withdrawal without a gluten-free diet. A control oesophago-gastroduodenoscopy was performed in one patient 6 months later and was considered normal. None of the patients showed evidence of cytomegalovirus in enterocytes or cytomegalovirus-positive viraemia. In conclusion, villous atrophy induced by MMF might be one of the mechanisms of diarrhoea. It is mandatory to differentiate coeliac disease from MMF-induced villous atrophy because, in the latter case, a gluten-free diet is not required.     

Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome

The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13–92) months and at treatment with MMF 104.7 (32–187) months. MMF was administered at a mean daily dose of 26.5 (16.6–31.3) mg/kg for 14.3 (6–45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.