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Efficacy of low-dose daily versus alternate-day prednisolone in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial

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Abstract

Background

While patients with frequently relapsing nephrotic syndrome (FRNS) are initially treated with long-term alternate-day prednisolone, relapses and adverse effects are common. In an open-label randomized controlled trial, we compared the efficacy of therapy with low-dose daily to standard alternate-day prednisolone in reducing relapse rates over 12-month follow-up.

Methods

Consecutive patients, aged 2–18 years, with FRNS were included. Following therapy of relapse, prednisolone was tapered to 0.75 mg/kg on alternate days. Stratifying for steroid dependence, patients were randomly assigned to prednisolone at 0.2–0.3 mg/kg daily or 0.5–0.7 mg/kg alternate day for 12 months. Relapses were treated with daily prednisolone, followed by return to intervention. Primary outcome was the incidence of relapses. Proportion with therapy failure (≥ 2 relapses in any 6 months or significant steroid toxicity) and sustained remission, cumulative prednisolone intake and adverse events were evaluated.

Results

Patients receiving daily prednisolone (n = 30) showed significantly fewer relapses than those on alternate-day therapy (n = 31) (0.55 relapses/person-year versus 1.94 relapses/person-year; incidence rate ratio 0.28; 95% CI 0.15, 0.52). Daily therapy was associated with higher rates of sustained remission at 6 months (73.3 versus 48.4%) and 1 year (60 versus 31.6%; log rank p = 0.013), lower rates of treatment failure at 6 months (3.3 versus 32.8%) and 1 year (6.7 versus 57.4%; p < 0.0001), and lower prednisolone use (0.27 ± 0.07 versus 0.39 ± 0.19 mg/kg/day; p = 0.003). Three and two patients need to receive the study intervention to enable sustained remission and prevent treatment failure, respectively.

Conclusions

In patients with FRNS, daily administration of low-dose prednisolone is more effective than standard-dose alternate day therapy in lowering relapse rates, sustaining remission, and enabling steroid sparing.

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Acknowledgments

Dr. M. Jeeva Sankar is acknowledged for the advice with statistical analysis.

Funding

Support for research on nephrotic syndrome has been possible through funding by the Indian Council of Medical Research (No. 5/7/1090/2013-RHN).

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Menka Yadav, Aditi Sinha, Priyanka Khandelwal, Pankaj Hari & Arvind Bagga

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  1. Menka Yadav
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  2. Aditi Sinha
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  3. Priyanka Khandelwal
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  4. Pankaj Hari
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  5. Arvind Bagga
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Corresponding author

Correspondence to Arvind Bagga.

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Approval was by the Institute Ethics Committee and informed written consent was obtained from either parent or patient before enrollment.

Conflict of interest

The authors declare that they have no conflict of interest.

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Yadav, M., Sinha, A., Khandelwal, P. et al. Efficacy of low-dose daily versus alternate-day prednisolone in frequently relapsing nephrotic syndrome: an open-label randomized controlled trial. Pediatr Nephrol 34, 829–835 (2019). https://doi.org/10.1007/s00467-018-4071-7

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