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Minimal lesion glomerulonephritis (MCD) represents approximately 15% of adult nephrotic syndromes. Although the exact etiology of MCD remains unknown, the activation of the immune system appears to play an important role in the pathogenesis. MCD is generally considered to be self-limiting with a benign course and an extremely low risk of progression to end stage renal disease. However, in adults the clinical manifestations are more severe. New approaches have been adopted in an attempt to limit nephrotic syndrome in adults with MCD. Therapy must be able to induce rapid remission, avoid relapses and limit adverse effects.
47-year-old woman in good health until the appearance of sloping edema with progressive weight gain. The haematochemical tests documented a picture of nephrotic syndrome in normal renal function. An extemporaneous urinalysis documented detectable proteinuria equal to 400 mg/dl and a 24/h urinalysis highlighted proteinuria in the nephrotic range equal to 12 g/day. She underwent a renal biopsy which showed MCD. The patient began steroid therapy with prednisone 75 mg/day. The steroid therapy was continued for 8 months with a slow and progressive decalage. At the end of steroid therapy, the patient presented sudden proteinuria of 10 mg/dl, with resolution of the nephrotic syndrome. However, one month after the suspension of therapy, the patient presented a recurrence of the nephrotic syndrome with extemporaneous proteinuria beyond the definition limits of our laboratory (>4,000 mg/dl). In light of the good initial response, the patient resumed steroid therapy which was continued for three months with regression of the clinical laboratory picture. Three months after suspension, a new relapse occurred compatible with nephrotic syndrome with 24/h proteinuria equal to 8 g/dl, total protidemia 4 g/dl.
Steroid therapy was initially resumed, initially with IV boluses for three days, methylprednisolone at a dosage of 750 mg/day, and followed orally with methylprednisolone 0.5 mg/day progressively reduced over the following thirty days. In light of the second recurrence of the nephrotic syndrome, after obtaining consent, it was decided to administer a first bolus of Rituximab at a dosage of 375 mg/m2. One month later, the proteinuria reduced to 4.3 g/day and a second bolus of Rituximab was administered at a dosage of 375 mg/m2. At the three-month follow-up, proteinuria reduced to 1.5 g/day and a third bolus of Rituximab was administered at a dosage of 375 mg/m2 in the third month.
48 months after the last administration of Rituximab, the proteinuria value is within the normal range of 0.3 g/day. The therapy administered was well tolerated. The patient did not require any maintenance immunosuppressive therapy.
Nephrotic syndrome in young adults is the clinical manifestation of several glomerular diseases including GNLM. The glomerular damage is immune-mediated through the activation of B lymphocytes. Steroid therapy for GNLM continues to be the cornerstone treatment at the onset of the disease, reaching remission after a few weeks, however some patients tend to present relapses with need for repeated cycles of steroid therapy alone or with the addition of other immunosuppressive drugs. Depending on the rate of relapses, these patients are classified as "steroid-dependent" and are exposed to possible adverse and serious effects of exposure to prolonged steroid therapy such as osteoporosis, cataracts, iatrogenic diabetes, growth retardation in children. The possibility of a specific therapeutic approach on B lymphocytes represents an evolution in the treatment of GNLM through a depletion of B lymphocytes that cause immune-mediated glomerular damage. The proposed therapeutic scheme with three boluses of Rituximab at a dosage of 375 mg/m2 at time zero, one month and three months allowed side effects and costs to be reduced to a minimum compared to the standard four-dose protocol used for both vasculitis and for the treatment of B-cell lymphomas. The tolerability and effectiveness of the proposed scheme could represent an alternative to conventional prolonged therapy with the steroid, avoiding all its side effects.