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Multicenter Study
. 2024 Dec;37(9):2551-2559.
doi: 10.1007/s40620-024-02076-6. Epub 2024 Sep 1.

Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome

Khairunnisa Mohamad  1 , Hadzliana Zainal  2 , Nur Arzuar Abdul Rahim  3 , Tengku Hasnita Tengku Hussain  4
Affiliations
Multicenter Study

Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome

Khairunnisa Mohamad et al. J Nephrol. 2024 Dec.

Abstract

Background: Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome.

Methods: A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis.

Results: Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjusted hazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency.

Conclusions: Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.

Keywords: Frequent relapse or steroid dependent; Idiopathic nephrotic syndrome; Predictors; Steroid-sparing agents.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Ethical approval: This study received ethical approval from Malaysia's Regulatory and Ethics Committees (Ref: 23–00815-NNF) and was conducted in compliance with the Declaration of Helsinki and the Malaysian Good Clinical Practice Guideline. Approval for publication has been obtained from the Director General of Health Malaysia. Human and animal rights: All procedures involving human participants adhered to the required ethical standards, and no animal studies were involved. Informed consent: Informed consent was waived due to the retrospective nature of the study, and the analysis utilized anonymous clinical data.

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