Rituximab for refractory cases of childhood nephrotic syndrome.

Rituximab has been used over the last decade as a rescue therapy for refractory cases of nephrotic syndrome (NS). Here we report the use of rituximab in four children with idiopathic steroid-resistant nephrotic syndrome (SRNS) with various histological backgrounds (two cases with focal segmental glomerulosclerosis, one case with IgM nephropathy, and one case with minimal change disease), who failed to respond to other immunsuppressions. Their median age (range) was 10 (8-11) years. NPHS2 genetic mutation was negative in all of them. All patients received a single dose of rituximab (375 mg/m(2)) and achieved complete B cell depletion as CD19 was <1% for 3 months following rituximab infusion. Only one patient achieved non-sustained remission as he relapsed after 4 months despite zero CD19 level. Patients received no further doses of rituximab as B cell was depleted in the peripheral circulation. We conclude that a single dose of rituximab was not effective in inducing sustained remission in children with idiopathic SRNS, despite complete B cell depletion in the peripheral circulation. Further doses might be indicated to deplete non-circulating B cells.

Intravenous pulse cyclophosphamide--is it effective in children with steroid-resistant nephrotic syndrome?

UNLABELLED: Treatment of steroid-resistant nephrotic syndrome (SRNS) remains a challenge to pediatric nephrologists. Recently, intravenous cyclophosphamide (IV-CPM) infusion was shown to be effective, safe, and economical for the treatment of SRNS, particularly minimal change disease (MCD), as it results in more sustained remissions, longer periods without proteinuria, and fewer significant side effects at a lower cumulative dose. A prospective study was conducted to evaluate IV-CPM infusions in the management of children with SRNS secondary to MCD or IgM nephropathy. Five patients with SRNS (4 IgM nephropathy and 1 MCD) received six monthly IV-CPM infusions at a dose of 500 mg/m(2). No patient achieved complete or sustained remission. Three patients attained partial remission, which was not sustained for more than 1 month post therapy. One patient progressed rapidly to end-stage renal disease during treatment. Side effects included vomiting in four patients and alopecia in one patient. CONCLUSION: IV-CPM pulse therapy at a dose of 500 mg/m(2) is unsuccessful in obtaining complete or sustained remission in children with SRNS secondary to IGM nephropathy or MCD. Further randomized controlled studies with higher doses are required.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium (Mg) and calcium (Ca) in the thick ascending limb of Henle's loop. We have studied seven Arab patients with this syndrome who belong to four different families. The mean age at first presentation was 1.5+/-1.3 years (range 0.1-3 years) and at diagnosis 5.9+/-4.3 years (range 0.5-12 years). The presenting features were convulsions and carpopedal spasms (5 patients), polydipsia and polyuria (2 patients), rickets (2 patients), and recurrent urinary tract infections (1 patient). Bilateral nephrocalcinosis was observed in all patients. All patients had hypomagnesemia with a mean serum Mg of 0.45+/-0.09 mmol/l, an inappropriately high urine Mg of 2.07+/-0.73 mmol/24 h or fractional excretion of 15.3+/-7.1%, high urine Ca excretion of 4.1+/-1.2 mmol/24 h or urine Ca to creatinine ratio of 2.6+/-1.6, and normal serum potassium level of 4.4+/-0.34 mmol/l. All patients received Mg supplements and thiazide but exhibited slow worsening of their kidney function. After a mean follow-up of 4.4+/-3.9 years, one patient progressed to end-stage renal failure (ESRF). In conclusion, we report seven Arab patients with FHHNC syndrome. The clinical and biochemical data were similar to previous reports. However, they tend to show a slower rate of progression to ESRF.

Levamisole treatment in steroid sensitive nephrotic syndrome.

OBJECTIVE: To evaluate the effectiveness of levamisole in maintaining remission in children with steroid-sensitive nephrotic syndrome (SSNS) who had a frequent relapsing or steroid-dependent course. METHODS: All children with SSNS who had a frequent relapsing or steroid-dependent course and were treated with levamisole between 1997 and 2001 at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia were reviewed. All patients were treated by the same steroid protocol used in our unit. Levamisole was considered effective if the patient successfully remained in remission on Prednisolone 0.5 mg/kg/48 hours or less. RESULTS: Nine children were treated with levamisole (3 mg/kg/48 hours) with median (range) age of 6 (3.5-10) years. Seven received levamisole for more than 6 (6-24) months and 2 were excluded because they did not adhere to treatment. Levamisole was effective in 4 patients (57%) with remarkable reduction in the number of relapses and the steroid maintenance dose. Renal biopsy was performed in 4 patients: 2 responders with biopsy findings of minimal change disease (MCD) and mesangioproliferative glomerulonephritis and another 2 non responders with biopsy findings of MCD and focal segmental glomerulosclerosis. No significant side effect was observed. CONCLUSION: Levamisole is effective in maintaining remission in steroid SSNS in Arab children and has few side effects.