Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population

Background Some kidney diseases tend to recur in the renal allograft after transplantation. We studied the risk of graft loss among primary renal diseases known for their high risk of recurrence and compared it with that of patients with hypoplasia and/or dysplasia. Methods Within the European Society of Paediatric Nephrology and European Renal Association and European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry, we studied children from 33 countries who received a kidney transplant before the age of 20 between 1990 and 2009. Patients were censored after 5 years of follow-up and cumulative incidence competing risk analysis was used to calculate survival curves. Results Patients with focal and segmental glomerulosclerosis (FSGS), haemolytic uraemic syndrome (HUS), membranoproliferative glomerulonephritis Type I or II (MPGN), IgA nephropathy or Henoch Schönlein Purpura (HSP/IgA) or systemic lupus erythomatosus (SLE) underwent pre-emptive transplantation significantly less often than patients with hypoplasia and/or dysplasia. The rate of living donation was lower among patients with FSGS and SLE than in patients with hypoplasia and/or dysplasia. In comparison with hypoplasia and/or dysplasia patients with a risk of 14.4%, the 5-year risk of graft loss was significantly increased in patients with FSGS (25.7%) and MPGN (32.4%) while it was not significantly increased in children with HUS (18.9%), HSP/IgA (16.3%) or SLE (20.3%). One-year graft survival strongly improved among HUS patients from 17.1% in 1995-1999 to 3.6% in 2005-2009 and was not accompanied by a decrease in the number of transplantations. Conclusion The risk of graft loss is increased among specific causes of renal failure with a high risk of post-transplant recurrence. It seems likely that, due to anticipation of such risk, physicians perform less pre-emptive transplantation and provide fewer grafts from living related donors in patients with these conditions. Improved risk stratification by physicians, resulting in the identification of patients with HUS at higher or lower risk of recurrence, might explain the much improved graft survival rate

Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor–dependent idiopathic nephrotic syndrome

In children with idiopathic nephrotic syndrome rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin-inhibitors. Long-term effects including number of repeated infusions to maintain remission are unknown. We treated with rituximab 46 consecutive children with idiopathic nephrotic syndrome lasting for at least one year (6.3±4.1 years), who were maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of three years (range 1–5). Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and two-year-remission probabilities were respectively 20% and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months respectively following the first and subsequent courses. Time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20 or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Rituximab can be safely and repeatedly used as prednisone and calcineurin-inhibitor-sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further research is needed to identify patients who will benefit most from rituximab therapy