Efficacy of higher-dose levamisole in maintaining remission in steroid-dependant nephrotic syndrome.

OBJECTIVE: Levamisole (LEV) has been used successfully on an alternate-day regime of 2.5 mg/kg in steroid-dependant nephrotic syndrome (SDNS) to maintain remission. This pilot study was carried out between 2010 and 2015 at a single center in Sri Lanka to evaluate the efficacy of LEV prescribed at 2.5 mg/kg daily, which is double the alternate-day dose. METHODS: Sequential children with SDNS, relapsing more than twice in the preceding 12 months and previously treated with LEV and low-dose alternate-day prednisolone (0.1-0.6 mg/kg) were recruited to the study. This group received LEV (2.5 mg/kg) daily with the same dose of alternate-day prednisolone for 1 year. Urine protein excretion was recorded by parents on a daily basis, and the presence of 3+ proteinuria on 3 consecutive days was considered a relapse. Full blood counts and liver function tests were performed every 3 months to monitor for adverse effects. RESULTS: Sixty-four children were enrolled into the study; six were excluded due to prescription of other immunosuppressive drugs. Median age was 7.9 years; 33 were boys. The number of relapse episodes was 163 [mean per patient 2.8 ± standard deviation (SD) 0.8] in patients on alternate-day LEV and 77 (mean 1.3 ± SD 0.9) for those on daily LEV during the 12-month period of observation. The P value 0.000 (according to the Wilcoxon signed-rank test) was <0.001. No major adverse events were noted. CONCLUSIONS: The prescription of daily LEV is effective and safe for maintaining SDNS remission.

Short courses of daily prednisolone during upper respiratory tract infections reduce relapse frequency in childhood nephrotic syndrome.

BACKGROUND: Relapses of childhood nephrotic syndrome (NS) are frequently precipitated by viral upper respiratory tract infections (URTIs). A review of the literature reveals that in patients with steroid-dependent NS on alternate day corticosteroids, a short course of daily corticosteroid therapy during the course of an URTI may reduce relapse frequency. OBJECTIVE: To assess the effect of a short course of low-dose corticosteroid therapy during the course of an URTI on relapse frequency in patients with steroid-sensitive NS who have not been taking any treatment for a minimum period of 3 months. METHODS: A double-blind placebo-controlled crossover trial was conducted on 48 patients with idiopathic NS who had not been receiving corticosteroid therapy for a minimum of 3 months. Patients were randomized into two groups. Group A received 5 days of daily prednisolone at 0.5 mg/kg at the onset of an URTI while group B received 5 days of placebo. Both groups were followed up for 1 year and the URTI-induced relapse frequency was noted. A crossover was performed during the next year, with group A receiving placebo and group B receiving prednisolone. RESULTS: Thirty-three patients completed the study. In the treatment group, 115 episodes of URTI led to 11 relapses while in the control group 101 episodes of URTI led to 25 relapses. There was no significant difference between the mean number of URTIs between the treatment and control groups. The treatment group had significantly less relapses compared to the control group (p = 0.014). Within the treatment group, 65.6% did not relapse, while the remainder had a single relapse. In contrast, only 40.6% of the control group remained in remission while 40.6% suffered a single relapse and 18.8% had two or more relapses. CONCLUSIONS: Prescribing a short course of daily corticosteroids during an URTI significantly reduces the frequency of URTI-induced relapse in patients with steroid-responsive NS who are off corticosteroid therapy.

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome.

OBJECTIVE: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis. STUDY DESIGN: To study the risks of HPA suppression, a modified low dose synacthen test (0.5 mug) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8-17.6 years) with NS receiving long-term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted. RESULTS: 20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow-up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01). CONCLUSIONS: Children with NS receiving long-term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.

Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis.

Clinical and histological data of children presenting with steroid-resistant nephrotic syndrome and renal biopsy showing focal and segmental glomerulosclerosis from 1980 with a follow-up of over 10 years were reviewed. There were 66 patients; 38 male and 28 female. Age at onset ranged from 0.4-14.1 years (mean 6.4). Tubular atrophy was present at first biopsy in 50/66, capsular adhesions in 35/66, glomerular tip lesions in 8/66 and mesangial expansion in 31/66 patients. In 51 children, cyclophosphamide was prescribed as the first cytotoxic agent, while 15 received cyclosporine A and complete remission was induced in 43 and 40% of the children, respectively. Complete and stable remission was maintained in 35 children, while 22 had reduction of proteinuria with symptomatic relief. Nine were refractory to cytotoxic therapy. Of the 35 patients who entered complete and stable remission, the renal survival was over 90%, while in the 31 non-responders it was 48% in 10 years. The multivariate analysis using unconditional logistic regression method identified the presence of mesangial expansion (p=0.011) and tip lesions (p=0.005) as the independent predictors of favourable response to cytotoxic therapy and the presence of renal impairment (p=0.008) and extensive focal segmental sclerosis (p=0.025) as independent predictors of unfavourable response.

The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome.

Childhood nephrotic syndrome (NS) is frequently characterized by a relapsing course. There is no uniform agreement about the precise stage at which a steroid-sparing agent should be introduced to control the disease. In order to evaluate the treatment strategies and outcome of steroid-sensitive NS over the last 2 decades, a retrospective notes review was undertaken in a cohort of children treated at Great Ormond Street Children's Hospital between 1980 and 2000. From a population of 863 children with NS referred, 509 had frequently relapsing or steroid-dependent disease and 261 children received at least one steroid-sparing agent. Cyclophosphamide was the first choice in 178 patients and in 114 no further steroid-sparing agent was needed. Levamisole was prescribed as the first steroid-sparing agent for 65 children and disease control was achieved in 30%. Cyclosporin A was prescribed in 61 children and sustained remission was induced in 69%. It is concluded that cyclophosphamide is a potent agent in inducing sustained remission in steroid-sensitive NS. Levamisole and cyclosporin A have emerged as attractive steroid-sparing agents. Complications and major side effects of treatment are infrequent but occasionally fatal.