Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study

Andrea Pasini, Cristina Bertulli, Luca Casadio, Ciro Corrado, Alberto Edefonti, GianMarco Ghiggeri, Luciana Ghio, Mario Giordano, Claudio La Scola, Cristina Malaventura, Silvio Maringhini, Antonio P Mastrangelo, Marco Materassi, Francesca Mencarelli, Giovanni Messina, Elena Monti, William Morello, Giuseppe Puccio, Paola Romagnani, Giovanni Montini, NefroKid Study Group, Andrea Pasini, Cristina Bertulli, Luca Casadio, Ciro Corrado, Alberto Edefonti, GianMarco Ghiggeri, Luciana Ghio, Mario Giordano, Claudio La Scola, Cristina Malaventura, Silvio Maringhini, Antonio P Mastrangelo, Marco Materassi, Francesca Mencarelli, Giovanni Messina, Elena Monti, William Morello, Giuseppe Puccio, Paola Romagnani, Giovanni Montini, NefroKid Study Group

Abstract

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate. Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course. Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction. Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%). Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens. Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

Keywords: age at onset; childhood idiopathic nephrotic syndrome; frequent relapsers; prognostic factors; steroid dependency; steroid treatment; total serum protein.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Pasini, Bertulli, Casadio, Corrado, Edefonti, Ghiggeri, Ghio, Giordano, La Scola, Malaventura, Maringhini, Mastrangelo, Materassi, Mencarelli, Messina, Monti, Morello, Puccio, Romagnani, Montini and the NefroKid Study Group.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Relapse-free survival curves: (A) Group A vs. Group B; (B) Prospective vs. Retrospective Cohort.
Figure 3
Figure 3
Cumulative prednisone doses. Total daily PRED dose, cumulative PRED dose at 12, 24 months and from the end of induction to the end of follow-up: Group A vs. B (A), prospective vs. retrospective cohort (B). All values are means ± SD (mg/m2) (C).
Figure 4
Figure 4
A sub-analysis of TTR and relapse risk was performed on Group A and B. On the left (A) for Group A, the relapse-free survival curve did not differ between the two subgroups. On the right (B) for Group B patients with higher TTR have a better curve, but the difference is not significant.
Figure 5
Figure 5
Relapse-free survival curves: (A) combined risk groups according to age (cut-off 5.3 years) and serum protein (cut-off 4.2 g/dl): Group 1, low-risk for both; Group 2, high-risk for total proteins only; Group 3, high-risk for age only; Group 4, high-risk for both; (B) induction prednisone dose in binary form (threshold 2,000 mg/m2).
Figure 6
Figure 6
Relapse-free survival curves according to induction prednisone dose in binary form (threshold 2,000 mg/m2), analyzed in each of the 4 combined risk groups based on age (cut-off 5.3 years) and serum protein (cut-off 4.2 g/dl): (A) Group 1, low-risk for both; (B) Group 2, high-risk for total proteins only; (C) Group 3, high-risk for age only; (D) Group 4, high-risk for both.

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