SP180
A RANDOMIZED CONTROLLED, DANISH MULTICENTER TRIAL IN MINIMAL CHANGE NEPHROPATHY: THE EFFICACY OF HIGH DOSE PREDNISOLONE VS. REDUCED PREDNISOLONE DOSE AND ACTIVATED VITAMIN D

INTRODUCTION AND AIMS: Minimal change nephropathy (MCN) is the cause of 10-25% of adult nephrotic syndrome. Current treatment involves high dose steroids. It is usually effective in bringing the patient into remission, but relapse rate is 30-70%. Many patients require long term steroid therapy associated with significant morbidity and mortality. Experimental evidence suggests that vitamin D regulates podocyte function which may be involved in the pathogenesis of proteinuria. Nephrotic syndrome is associated with low vitamin D levels. Treatment with activated vitamin D reduces proteinuria in both animal and human studies. Repetitive samplings of non-stimulated saliva provide a good estimate of prednisolone turnover. This may allow for individualized dosing of prednisolone in order to reduce adverse effects without compromising efficacy. The aim of this trial is to examine the efficacy of a reduced prednisolone dose combined with activated vitamin D for the induction of remission and frequency of relapse in MCN compared to standard treatment with high dose prednisolone. The hypothesis is that treatment with reduced prednisolone and activated vitamin D is not inferior to standard high dose prednisolone in inducing remission, and treatment with reduced prednisolone dose and activated vitamin D has less adverse effects.

METHODS: A randomized, open-labelled, multicenter trial comparing the efficacy of prednisolone 1mg/kg/d to prednisolone 0.5mg/kg/d plus activated vitamin D 0.5µg/d in patients with primary MCN using a non-inferiority design. Primary endpoints are the frequency of remission after 16 weeks and the time to remission. Secondary endpoints are the frequency of relapse and objective and subjective side effects to treatment. Blood and urine samples are collected throughout the study period to establish remission and relapse. Saliva test are preformed to examine individual prednisolone turnover. Clinical examination and patient questionnaire measure adverse effects. Follow up is 1 year from remission. A total of 96 patients from all renal departments in Denmark will be included.

RESULTS: The trial has been approved by The Danish Data Protection Agency (record no.: 1-16-02-38-17), The Danish Medicines Agency (record no.: 2017-001206-16) and the Research Ethics Committees (record no.: 1-10-72-178-17), and accepted as part of a Ph.D.-trial at Aarhus University. The inclusion of patients will begin primo 2018.

CONCLUSIONS: If successful, this should significantly reduce the serious adverse effects associated with treatment and change current guidelines for the management of this common cause of nephrotic syndrome in both children and adults. Furthermore, the study will examine the feasibility of personalized treatment regimens based on the individual prednisolone metabolic turnover. The trial will include additional analyses to study disease mechanisms and potentials for new, supportive treatment in nephrotic syndrome and will facilitate collaboration between nephrology centers in Denmark.