Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome.

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny.

Double filtration plasmapheresis - 10-year pediatric experience as an alternative to plasma exchange.

BACKGROUND: Double filtration plasmapheresis (DFPP) is more selective at removing antibodies compared to plasma exchange (PE), thus reducing the need for replacement blood products. METHODS: We retrospectively analyzed the records of all pediatric patients whom DFPP had been performed. RESULTS: In total, 30 patients were treated with DFPP. Data were available for 436 sessions in 23 patients. Patients had a median of 6 (1-161) sessions. Age at start of treatment was 13.9 years (2.2-19.2) and weight 46 kg (13.4-82.8). Six patients were treated for antibody mediated rejection; 1 had full recovery, 1 CKD stage 4 and 4 required dialysis. Two patients were treated for recurrence of focal segmental glomerulosclerosis (FSGS) with good response. One successfully had an ABO-incompatible kidney transplantation. Five had anti-glomerular basement membrane disease; 3 had complete recovery, 1 CKD and 1 required transplantation. Three had granulomatosis with polyangiitis; 1 with full recovery, 1 had CKD and 1 required dialysis. Two had Type-2 Membrano-proliferative glomerulonephritis, 1 successfully treated, the other needing dialysis. One treated for rapidly progressive MPO-glomerulonephritis required dialysis. Other indications were Myasthenia Gravis, Guillain-Barré disease and autoimmune limbic encephalitis. Excluding FSGS patients (with >100 sessions), one patient had cryoprecipitate, 2 had blood transfusions, no other blood products were required. Minor complications were seen in 13 sessions (8.4%). No major complications were seen. CONCLUSION: DFPP is a safe, well tolerated form of apheresis that appears to have comparable outcomes to that of PE, without the routine need of replacement blood products.

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome.

OBJECTIVE: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution. METHODS: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells. RESULTS: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups. CONCLUSIONS: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.

Peritoneal Dialysis Catheter Removal Post-Transplant - A Rare Case of Delayed Bowel Perforation.

Peritoneal dialysis (PD) is a well-established form of renal replacement therapy and the practice of leaving catheters in situ post-transplantation widely accepted. We present a rare complication: a child presenting with anal protrusion of the PD catheter.The patient is an 11-year-old boy with a background of renal dysplasia and congenital cutis laxa. Twenty-three weeks after dialysis was commenced, the patient underwent a renal transplant. Thirteen weeks post-transplant, the patient felt an unusual sensation after defecation. The curled end of the catheter was seen protruding from the anus. He was admitted, and investigations showed stable graft function, with abdominal X ray showing no free air.Intraoperative findings showed a small perforation of the sigmoid colon sealed off by adherence of several small intestinal loops. This was repaired laparoscopically after removal of the distal part of the catheter per rectum. No peritoneal contamination was seen. He was treated with 5 days of intravenous antibiotics and gradual introduction of enteral feeds. His graft function remained stable throughout.Timing of catheter removal varies, from the time of transplantation to over 3 months post-transplantation. Bowel perforation due to PD catheter insertion is rare and tends to occur at the time of insertion. Anal protrusion of a PD catheter in childhood is extremely rare and unrecorded in a pediatric patient with a connective tissue disorder. Our case highlights that serious complications can occur in the period between transplantation and elective PD catheter removal and that, in the immunocompromised patient, signs can be subtle.