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Nephrotic syndrome relapse: need for a better evidence based definition
  1. H Narchi
  1. Paediatric Department, Sandwell General Hospital, West Bromwich B71 4HJ, UK;

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    Despite the occurrence of relapses, steroid sensitive nephrotic syndrome (SSNS) has a good long term prognosis. As it often heralds a clinical relapse, significant proteinuria (+++ or more on albustix) for ⩾3 consecutive days (simplified as P3D in this letter) defines a relapse, resulting in steroid therapy before the onset of oedema. Proteinuria may be triggered by viral infections1 and does not always develop into a relapse.2

    We have observed 24 consecutive episodes of asymptomatic P3D, without oedema, occurring during a viral illness, in four children (two boys, two girls, age range 2–5 years) known to have SSNS. In eight of these episodes, the families refused to rush with steroid therapy; serum albumin level remained >30 g/l in the three where measured, and the proteinuria resolved between 5 and 10 days. Sixteen other episodes occurred in three children, who were treated as relapses; all three were later labelled as frequent relapsers and started on long term steroid therapy. None required renal biopsy. One child required cyclophosphamide and two required levamisole therapy; a rash occurred in one. None could be vaccinated against varicella while on steroid therapy; all required varicella zoster immunoglobulin injections after contact with chickenpox, and one child developed varicella while on steroids and required acyclovir therapy.

    In this series, 33% (exact binomial 95% confidence intervals 15% to 55%) of the P3D episodes were not relapses: there was no hypoalbuminaemia or oedema, and they resolved spontaneously within 5–10 days. We cannot ascertain how many of the remaining episodes were genuine relapses, as some may well have also resolved spontaneously after a few days. Although not blinded or controlled, this observational study challenges the current definition of relapse by the sole presence of P3D, confirming studies where up to one third of such episodes did not develop into a relapse and where waiting 10 days before starting therapy did not influence the course.2 Defining a relapse only by P3D may therefore lead to unnecessarily treating 15–55% of affected children, and may cumulatively lead to over-diagnosing frequent relapses, resulting in unnecessary renal biopsy, prolonged steroid courses, and therapy with cyclophosphamide, cyclosporin, and levamisole, with their potential side effects.

    As the natural history of isolated proteinuria in children with SSNS remains largely unknown, there is a clear and urgent need for larger prospective controlled studies in order to define relapses more accurately.