Steroid-dependent Minimal Change Nephrotic Syndrome Research Articles

Retrospective single-arm cohort study of steroid-dependent minimal change nephrotic syndrome treated with very low-dose rituximab.

Conclusions regarding the best rituximab (RTX) dose to maintain remission and reduce immunosuppressant dependence in adult patients with steroid-dependent minimal change nephrotic syndrome (MCNS) are inconsistent. We report the first low-dose (< 375 mg/m2 BSA) RTX therapy, administered once every 6 months. In this retrospective single-arm cohort study, we investigated the safety and efficacy of low-dose RTX therapy to reduce and ultimately stop prednisolone (PSL) and cyclosporine (CyA) treatment. 13 patients (8 men and 5 women; aged 16 - 65 years; 8-year median treatment history; 12 patients concurrently taking CyA) with steroid-dependent MCNS were chosen to maintain remission following low-dose RTX (200 mg/body) administration. The median period of subject observation following the first RTX dosing was 34 months (cumulative RTX dose: 400 - 1,400 mg). RTX significantly reduced PSL and CyA doses during the final observation in each subject (median dose: PSL 15→0 mg/day, p = 0.0002; CyA 80→0 mg/day, p = 0.0005). All patients maintained complete remission after discontinuing both drugs for a median complete remission (CR) maintenance period of 25 months. One patient showed relapse following the first RTX dose, but a temporary increase in PSL and CyA dose restored the remission. No serious RTX-related adverse effects were observed. Even with MCNS remission, peripheral CD19-positive cell count was not depleted in 90.5% of all cases. Low-dose RTX therapy appears to be effective in maintaining remission and reducing immunosuppressant doses in patients with steroid-dependent MCNS, which might involve a B-cell-independent mechanism.

Rituximab as a Therapeutic Option for Steroid-Sensitive Minimal Change Nephrotic Syndrome in Adults.

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15 days in patients with steroid-dependent MCNS. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, we must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment. In this review, we highlight recent studies and discuss the effects of these studies on the management of patients with MCNS in adults.

Single dose of rituximab in children with steroid-dependent minimal change nephrotic syndrome.

Rituximab (RTX) can be used in children with nephrotic syndrome, particularly in those with steroid-dependent nephrotic syndrome (SDNS). However, at present there is no unified standard of how to use RTX, with regard to the amount of doses and frequency, in children with nephrotic syndrome. The study aimed to investigate the therapeutic efficacy of a single dose of RTX in children with steroid-dependent minimal change nephrotic syndrome (SD-MCNS). The patients with biopsy-proven minimal change disease (MCD) and clinical features of SDNS received a single dose of RTX (375 mg/m2). The toxicity and side effects of RTX were also observed. The study included 19 patients (10 males and 9 females). Follow-up of the patients was 1-50 months (28.1±16.6 months). B-cell depletion was achieved with RTX infusion (CD20<0.5%) and lasted 1-6 months (mean, 2.92±1.57 months). During follow-up, 10 patients remained in complete remission and did not relapse without administration of oral steroids or immunosuppressants for 4-50 months (mean, 30.1±12.6 months), despite recovery of the B-cell count. Nine patients relapsed in the process of reducing steroids, thus, treatment was maintained at a lower dosage (T=0, P<0.05) than prior to use of RTX. The number of relapses also decreased significantly (T=95, P<0.05). Five of the patients relapsed after stopping steroid for several months. At the end of follow-up, the efficacy of a single induction of RTX was 47.4% (9/19). There were no significant side effects associated with administration of RTX. In conclusion, RTX is a safe and effective alternative for children with SD-MCNS. RTX is an effective treatment for the rapid induction of remission and reduces relapse and steroid dependency. A single dose of RTX for children with SD-MCNS is recommended for rapid induction of remission, reduction of long-term steroid dosage, and decrease in the number of relapses, as it has few side effects.

ステロイド依存性微小変化型ネフローゼ症候群に対するシクロスポリン1 日1 回投与法による初回治療の有効性と安全性の検討

小児のステロイド依存性微小変化型ネフローゼ症候群(SDNS)において，シクロスポリン(CsA)は非常に有効な免疫抑制薬であり，1 日2 回の食前内服が推奨されている。今回，SDNS 患児においてシクロスポリン1 日1回投与法による初回治療(以下1 回法，目標内服2 時間濃度600～800 ng/ml)を試みた23 例について有効性と安全性について，後方視的に検討を行った。1 回法はSDNS からの脱却率が65％，2 年間の無再発率は34.8％であった。さらに，1 回法におけるCsA 投与量は平均2.6 mg/kg であり，通常の2 回法より明らかに減量することが可能であった。しかし，1 回法も1 例(8.3％)に間質線維化を認めたため，2 回法と同様プロトコール腎生検は必要であると考えられた。SDNS 患児に対して，1回法はアドヒアランスの向上とCsA 投与量の削減が可能な有効な治療と思われた。

Amelioration of the adverse effects of prednisolone by rituximab treatment in adults with steroid-dependent minimal-change nephrotic syndrome

We previously demonstrated the efficacy of single-dose 6-monthly rituximab infusions in 25 adults with steroid-dependent minimal-change nephrotic syndrome. Herein, we assessed the safety of rituximab treatment and its effect in ameliorating the adverse effects of prednisolone (PRED) in a larger study sample. We treated 54 adult patients with four single-dose 6-monthly infusions of rituximab (375 mg/m(2) BSA per dose). We compared the adverse effects of PRED (osteoporosis, hypertension, and diabetes mellitus) between the first rituximab infusion (baseline) and the end of the 24-month observation period. In addition, we examined the adverse effects of rituximab during the same period. The PRED dose was significantly lower at 24 months than at the baseline. The bone density was significantly higher at 24 months as compared to the baseline value (Z score -1.8 vs. -1.1; p < 0.05). Blood pressure at 24 months was significantly lower than that at the baseline (120.9/74.4 vs. 111.8/70.3 mm Hg; p < 0.05). Eight patients with diabetes mellitus showed improved glycemic control at 24 months as compared to that at the baseline. There were no severe adverse effects of rituximab. However, mild infusion reactions occurred in 31 patients (57%). The frequency of the infusion reactions decreased significantly with every successive infusion. Rituximab treatment was effective and safe in patients with steroid-dependent nephrotic syndrome, allowed reduction of the PRED dose, and ameliorated the adverse effects of PRED. It may be preferentially used in patients at a risk of the adverse effect of PRED.

Long-term prognosis of adult patients with steroid-dependent minimal change nephrotic syndrome following rituximab treatment.

This study was to evaluate the long-term efficacy and safety of a single-dose rituximab regimen rituximab treatment in adult patients with steroid-dependent minimal change nephrotic syndrome (MCNS).We conducted a prospective cohort study with historical controls to evaluate the effect of single-dose infusions of rituximab at 375 mg/m2 BSA per dose administered at intervals of 6 months for a period of 24 months. At the end of the 24-month period, the patients were divided into the treatment continuation (n = 20) and treatment discontinuation (n = 5) groups according to their intention to continue/discontinue the treatment.A significant reduction in the total number of relapses was observed during the 24-month period after the first rituximab infusion as compared with that during the 24-month period before the first rituximab infusion (108 vs. 8, P < 0.001). Complete remission was induced/maintained in all patients from 12 to 24 months after the first rituximab infusion. In regard to the clinical course after 24 months, 4 of the 20 patients in the treatment continuation group discontinued the rituximab treatment after the fifth infusion and 2 patients discontinued the treatment after the sixth infusion. However, complete remission was maintained in all the 20 patients of this group during the 12-month observation period after the first four single-dose rituximab infusions. On the other hand, 1 of the 5 patients in the treatment discontinuation group developed relapse during the observation period after the first four rituximab infusions, and the rituximab treatment was resumed.In our trial, rituximab therapy was associated with maintenance of complete remission. Complete remission was maintained even in most of the patients who showed B-cell repletion after discontinuation of rituximab therapy. Thus, rituximab may be considered as a radical therapeutic agent for patients with steroid-dependent MCNS.

Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease

Development of steroid dependency in patients with nephrotic syndrome may require a long-term multi-drug therapy at risk of drug toxicity and renal failure. Rituximab treatment reduces the steroid dosage and the need for immunosuppressive therapy in pediatric patients. Here we retrospectively analyze the efficacy and safety of rituximab in adult patients with steroid-dependent minimal change disease. To do this, we analyzed the outcome of all adult patients treated with rituximab for steroid-dependent minimal change nephrotic syndrome over a mean follow-up of 29.5 months (range 5.1-82 months). Seventeen patients with steroid-dependent or frequently relapsing minimal change nephrotic syndrome, unresponsive to several immunosuppressive medications, were treated with rituximab. Eleven patients had no relapses after rituximab infusion (mean follow-up 26.7 months, range 5.1-82 months) and nine of them were able to come off all other immunosuppressive drugs and steroids during follow-up. Six patients relapsed at least once after a mean time of 11.9 months (mean follow-up 34.5 months, range 16.9-50.1 months), but their immunosuppressive drug treatment could be stopped or markedly reduced during this time. No adverse events were recorded. Thus, rituximab is efficient and safe in adult patients suffering from severe steroid-dependent minimal change disease. Prospective randomized trials are needed to confirm this study.

Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults

Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases. To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion. A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse. Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.

Nephrotoxicity of once-daily cyclosporine A in minimal change nephrotic syndrome

Although once-daily cyclosporine (CsA) therapy may have greater nephrotoxic-sparing effects than standard twice-daily therapy, little information is available in children with steroid-dependent minimal change nephrotic syndrome (MCNS) regarding histological analysis after long-term once-daily administration. A prospective study of the clinical efficacy and comparison between pre- and post-treatment renal biopsy findings in ten children (mean age, 8.8 years) with steroid-dependent MCNS who were administered once-daily CsA therapy for more than 24 months (mean ± SD, 30 ± 3.7) was performed in Saitama Children's Medical Center. Administration of once-daily CsA therapy (mean dose, 2.8 ± 0.6 mg/kg/day; mean C2 levels, 670 ± 64 ng/ml) resulted in a significant reduction in the median relapse rate from 4.6 to 0.2 times per year, and five patients did not experience a relapse of NS. Furthermore, mean threshold of prednisolone dose significantly reduced from 1.2 to 0.02 mg/kg on alternate days. However, two patients showed evidence of chronic CsA nephrotoxicity (CsAN). Once-daily CsA therapy appears to be effective in children with steroid-dependent MCNS. However, follow-up renal biopsies should be performed to investigate the presence of CsAN after more than 24 months of treatment with once-daily regimen as well as with the conventional twice-daily regimen.

Rituximab and minimal change nephrotic syndrome: a therapeutic option

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10-15days in patients with steroid-dependent nephrotic syndrome. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, physicians must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent or steroid-resistant MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment.

Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine

Rituximab (RTX) has been successfully used as a rescue therapy in children with steroid-dependent nephrotic syndrome (SDNS). However, little is known regarding maintenance therapy after a successful response to RTX in such patients. The efficacy and safety of a single RTX infusion (375 mg/m(2)) were assessed in ten patients who had persistent SDNS associated with minimal-change disease (MCD) despite the long-term use of cyclosporine (CsA). The mean follow-up after RTX infusion was 17 months. Applying RTX resulted in a significant reduction in the mean prednisolone (PSL) dose from 0.39 +/-0.18 to 0.15 +/- 0.14 mg/kg per day. The mean 12-month relapse rates significantly decreased from 4.1 +/- 1.7 to 0.6 +/- 0.6. All but one patient who had continued CsA as maintenance therapy after a single RTX infusion were able to withdraw from PSL without any relapses during the study period, whereas the remaining five patients who discontinued CsA experienced relapses after CD19 cells re-emerged, leading to the reintroduction of CsA or an additional RTX infusion. Infusion reactions occurred in five of ten patients. These data indicate that a single RTX infusion may improve response to CsA in patients with persistent SDNS due to the phenomenon of secondary resistance to CsA.

Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children.

Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term adverse effects of persistent nephrotic syndrome and immunosuppressive medications, focusing on renal function, growth, obesity, osteoporosis, hypertension, ocular complications, and fertility in adult patients with biopsy-proven childhood-onset MCNS. Molecular analysis was performed to evaluate a possible association of a complicated course of MCNS with podocyte gene mutations. We performed a prospective clinical examination of 15 adult patients that included serum and urine analysis; dual-energy x-ray absorptiometry; ophthalmologic examination; semen examination; and molecular analysis of NPHS1, NPHS2, CD2AP, and ACTN4 genes. All patients had normal GFR. Most frequent long-term complications were hypertension (in seven of 15 patients) and osteoporosis in one third of patients. Oligozoospermia was found in one patient, reduced sperm motility in four of eight patients, and teratozoospermia in six of eight patients. Ophthalmologic examination revealed myopia in 10 of 15 patients and cataract in three of 15 patients. Children with MCNS that persists after puberty are at risk for complications such as osteoporosis, hypertension, cataract, and sperm abnormalities. Our study underscores a need for more effective and less toxic therapies for relapsing MCNS.

Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome

Treatment of adults with steroid-dependent minimal change nephrotic syndrome (SD-MCNS) can be a significant challenge. Cyclophosphamide (CYC) and cyclosporin (CYA) are often effective steroid-sparing agents. Tacrolimus (TAC) may be another treatment option. This open, prospective cohort study enrolled Chinese adults with SD-MCNS. At the start of the study, we administered TAC or intravenous CYC together with prednisone (0.5 mg/kg/day), the dose of which was tapered off throughout the study. The TAC cohort received oral TAC (target trough blood level of 4-8 ng/ml) for 24 weeks and the CYC cohort received intravenous CYC (750 mg/m(2) body surface) once every 4 weeks for 24 weeks. Twenty-six patients met the criteria for enrollment (14 patients in the CYC group and 12 patients in the TAC group). One patient from each group discontinued treatment because of a drug-related side effect. Complete remission (CR) after the 24-week therapeutic period was 76.9% (10/13) in the CYC group and 90.9% (10/11) in the TAC group. The mean time required for CR in the TAC group was significantly less than in the CYC group (P = 0.031). Eight of 13 (61.5%) patients in the CYC group and 8 of 11 (72.7%) patients in the TAC group successfully stopped steroids and changed their status from steroid dependence. Sixty percent (6/10) of the CYC patients and 50% (5/10) of the TAC patients who achieved CR maintained remission during the follow-up period of 23.0 +/- 10.1 months. Four (40%) CYC patients and five (50%) TAC patients experienced relapses, and two CYC patients experienced frequent relapses. A 24-week course of TAC is a favorable steroid-sparing agent for treatment of Chinese adults with SD-MCNS. Therapy with TAC accompanied by a tapering dose of prednisolone appears to yield quicker remission than treatment with CYC together with prednisone.

海外論文紹介 : Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome

成人ステロイド依存性ネフローゼ症候群 (SDNS) において, cyclophosphamide (CYC) とcyclosporin (CYA) はステロイド薬減量効果を期待できる薬剤とされるが, tacrolimus (TAC) も有用かどうかを前方視的に検討した。 26名の成人SDNSを2群に分け, 14名はプレドニン (0.5 mg/kg) に6ヵ月間, 月1回のCYCパルス療法 (750 mg/m2) 併用 (iv-CYC) を, 12名は同量のプレドニンに6ヵ月間のTAC (trough値を4～8ng/ml) 療法を併用, プレドニンは経過中に漸減中止とした。 経過中各群で1名ずつが副作用のため離脱したが, 6ヵ月間の治療終了時点でCYC群は76.9% (10/13名), TAC群は90.9% (10/11名) が完全寛解に至った。完全寛解に至るまでの期間はTAC群で有意に短かった (p=0.031)。CYC群の8名 (61.5%), TAC群の8名 (72.7%) がステロイド薬中止可能となった。治療期間終了後平均23.0±10.1ヵ月の観察期間で, 治療により完全寛解となったCYC群の60% (6/10名), TAC群の50% (5/10名) で寛解が維持された。CYC群の4名, TAC群の5名は再発があり, CYC群の2名は頻回再発となった。 6ヵ月間のTAC療法はCYCよりも早期に寛解導入が可能であり, 有意なステロイド薬減量効果が確認された。

Tacrolimus effective in steroid-dependent minimal change nephrotic syndrome

Tacrolimus effective in steroid-dependent minimal change nephrotic syndrome

Rituximab: effective treatment for severe steroid-dependent minimal change nephrotic syndrome?

Rituximab: effective treatment for severe steroid-dependent minimal change nephrotic syndrome?

Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome

Steroid resistance and steroid dependence constitute a major problem in the treatment of minimal-change disease and focal segmental glomerulosclerosis (FSGS). Cyclophosphamide and cyclosporine are well-established alternative immunomodulating agents, whereas data on FK 506 (tacrolimus) are rare. The present work provides data from 10 patients of an open, monocentric, non-randomized, prospective trial. Five patients with steroid-dependent minimal-change nephrotic syndrome, 1 patient with steroid-refractory minimal-change disease and 4 patients with steroid-refractory FSGS were started on tacrolimus at trough levels of 5 10 microg/l. In case of steroid-dependence, prednisolone was tapered off in presence oftacrolimus within one month. Within 6 months, complete remission was achieved in 5 patients (50%) and partial remission in 4 patients (40%), yielding a final response rate of 90%. One patient was primarily resistent to tacrolimus (steroid-refractory minimal-change), another patient became secondarily resistant to tacrolimus after an initial remission (steroid-refractory FSGS). Average proteinuria significantly decreased by 77% from 9.5 +/- 1.4 - 2.2 +/- 1.1 g/day (p < 0.01). Serum protein significantly raised from 55.0 +/- 1.9 - 64.6 +/- 1.9 g/l (p < 0.01). Tacrolimus induced non-significant increases of blood glucose (4.9 +/- 0.1 - 5.1 +/- 0.2 mmol/l), systolic blood pressure (131.4 +/- 7.1 - 139.0 +/- 7.6 mmHg) and creatinine (93.2 +/- 13.9 103.2 +/- 15.3 mmol/l). Five patients have been tapered off tacrolimus so far, nephrotic syndrome relapsed in 4 of them (80%). Relapse occurred at tacrolimus levels between 2.6 and 6.9 ng/ml. Our data suggest that tacrolimus may be a promising alternative to cyclosporine both in steroid-resistant and steroid-dependent nephrotic syndrome.

Long-term results of two unconventional agents in steroid-dependent nephrotic children

Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children.

In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3-15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome.

We describe a prospective study of 2-year moderate-dose cyclosporin (CS) treatment in 13 children with steroid-dependent minimal change nephrotic syndrome (MCNS). CS treatment was commenced at 100-150 mg/m2 per day after remission was attained with prednisolone therapy, was adjusted to a target trough level of 100 ng/ml, and was administered for 2 years. The number of relapses during CS treatment significantly decreased compared with before CS treatment, all patients were able to discontinue prednisolone therapy, and steroid toxicity was reduced; 54% of patients remained in remission during CS treatment. Renal biopsies performed before CS treatment all showed MCNS without tubulointerstitial lesions. Creatinine clearance and urinary beta 2-microglobulin levels during CS treatment were normal in all patients, but renal biopsies performed after CS treatment revealed chronic CS nephrotoxicity in 7 patients. Clinical data, including CS dose and CS trough blood levels, were not significantly different between patients with and without nephrotoxicity. In conclusion, 2-year moderate-dose CS treatment in children with steroid-dependent MCNS is effective in preventing relapse and decreasing steroid toxicity. This treatment can, however, result in a high incidence of chronic nephrotoxicity. Renal function is not a reliable indicator of chronic CS nephrotoxicity. Renal biopsy is therefore necessary to monitor chronic CS nephrotoxicity.