Re-treatment with high-dose prednisolone after rituximab infusion for childhood-onset steroid-resistant nephrotic syndrome

Abstract

Sirs, We read with great interest the article titled “Rituximab treatment combined with methylprednisolone pulse therapy and immunosuppressants for childhood steroid-resistant nephrotic syndrome” by Kamei et al., which has recently appeared in Pediatric Nephrology [1]. In this retrospective observational study of ten childrenwith refractory steroid-resistant nephrotic syndrome (SRNS), seven patients (70 %) achieved complete remission after receiving multiple courses of methylprednisolone pulse therapy (MPT) and immunosuppressive agents administered after one to four doses of rituximab (RTX). Although we agree with their speculation that a RTX infusion may improve the response to various immunosuppressants, such as steroids and cyclosporine A, little information is currently available on the optimal therapeutic protocol for children with refractory SRNS after administration of the biological agent. We previously described a 2-year-old girl with refractory SRNS resistant to nine courses of MPT (total 27 treatments) and cyclosporine A (6–7 mg/kg/day) following RTX infusion. Interestingly, the patient went into complete remission after re-treatment with conventional high-dose prednisolone (PSL, 2 mg/kg/day) administered after an additional RTX infusion within 2 weeks [2]. Recently, we encountered a SRNS patient resistant to multiple courses of MPTand mycophenolate mofetil who also achieved complete remission after re-treatment with high-dose PSL administered after an RTX infusion within a short period of time. This patient, an 8-year-old boy, presented with a 2-week history of significant weight gain and generalized edema. His medical history was significant for chronic kidney disease (estimated glomerular filtration rate 60–70 ml/min/1.73 m) as he had experienced septic shock associated with pneumococcal meningitis at the age of 1 year. On admission, a physical examination showed generalized edema, abdominal distention, and a blood pressure of 111/72 mmHg. His weight was 22.2 kg, which was increased by 2 kg compared to his dry weight. Laboratory investigations were as follows: white blood cell count, 72,000/mm; hemoglobin, 13.7 g/dl; hematocrit, 39.2 %; platelets, 221,000/mm; blood urea nitrogen, 23 mg/dl; serum creatinine, 0.61 mg/dl; sodium, 137 mmol/l; potassium, 4.4 mmol/l; chloride, 107 mmol/l; calcium, 7.7 mg/dl; phosphorous, 4.8 mg/dl; total protein, 3.9 g/dl; albumin, 1.6 g/dl; total cholesterol, 404 mg/dl; serum immunoglobulin G, 202 mg/dl, C3, 105 mg/dl, and C4, 18 mg/dl. Tests with antihepatitis B surface antigen, antihepatitis C antibody, and antinuclear antibody were negative. Urinalysis showed 1+ occult blood and 3+ protein by dipstick. The 24-h urine protein excretion was 4.9 g. Based on these findings, a presumptive diagnosis of idiopathic NS in the course of chronic renal insufficiency was made, and treatment with high-dose PSL (2 mg/kg/day) was initiated without a significant reduction in the amount of proteinuria. Persistent nephrotic-range proteinuria for more than 4 weeks with conventional steroid therapy prompted us to perform a renal biopsy with histology, which showed ischemic glomerular obsolescence. Since nephrotoxic drugs such as cyclosporine A were contraindicated based on the histological findings, the patient was treated with MPT (20 mg/kg/day for 3 consecutive days per week) for 3 weeks, followed by mycophenolate mofetil (30 mg/kg/day) and alternate-day low-dose PSL. However, proteinuria did not return to baseline values. After a single infusion of RTX (375 mg/m), a second course of high-dose PSL (2 mg/kg/ S. Fujinaga (*) Division of Nephrology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki-ku, Saitama City, Saitama 339 8551, Japan e-mail: f_shuich@d2.dion.ne.jp