Revisiting Chlorambucil: A Pragmatic Approach to Childhood Steroid-Resistant Nephrotic Syndrome with Historical and Contemporary Insights

Advisor Doctor and Expert Trainer, Baghdad Medical City and Iraqi Ministry of Health Baghdad, Iraq

*Corresponding Author: Aamir Jalal Al-Mosawi, Advisor Doctor and Expert Trainer, Baghdad Medical City and Iraqi Ministry of Health Baghdad, Iraq, Email: [email protected]

Received Date: April 02, 2026

Published Date: May 22, 2026

Citation: Al-Mosawi AJ. (2026). Revisiting Chlorambucil: A Pragmatic Approach to Childhood Steroid-Resistant Nephrotic Syndrome with Historical and Contemporary Insights. Mathews J Case Rep. 11(2):224.

Copyrights: Al-Mosawi AJ. © (2026).

ABSTRACT

Background: Childhood steroid resistant nephrotic syndrome has traditionally relied on renal biopsy for therapy guidance; however, in children under six years old with typical features of idiopathic nephrotic syndrome, the likelihood of minimal change disease is high. This paper discusses the dynamic nature of renal histopathology in steroid resistant nephrotic syndrome, where transitions between minimal change disease, focal segmental glomerulosclerosis, and diffuse mesangial proliferation, are well-documented; suggesting that initial biopsy results may not definitively predict disease progression. Chlorambucil, an alkylating agent introduced in 1955, has shown effectiveness in treating difficult cases of nephrotic syndrome. Several studies from the 1970s demonstrated that chlorambucil, when used in combination with prednisone, provided high rates of sustained remission in children with steroid-dependent or frequently relapsing nephrotic syndrome. However, concerns about its long-term safety, including gonadal toxicity and the potential risk of malignancy, must be considered. This paper aims to examine a pragmatic approach to managing young children with idiopathic steroid-resistant nephrotic syndrome without immediate renal biopsy. The approach leverages the high likelihood of minimal change disease in early childhood and highlights histopathologic variability, particularly the transitions between minimal change disease, focal segmental glomerulosclerosis, and diffuse mesangial proliferation. The paper also presents a representative case treated successfully with chlorambucil and offers expert commentary on its potential relevance in modern clinical settings. Patients and Methods: An archival case, seen before 2003, describes a 20-month-old male child with steroid-resistant idiopathic nephrotic syndrome. The patient initially responded to corticosteroid therapy but developed a second episode of nephrotic syndrome at 18 months, which was resistant to corticosteroid therapy. The patient was treated with chlorambucil at a dose of 0.2 mg/kg/day, leading to complete remission within five weeks. No infectious triggers for steroid resistance were identified. Results: The treatment with chlorambucil led to complete remission, defined by the resolution of edema and disappearance of significant proteinuria. Follow-up was lost after eight weeks of treatment. The choice of chlorambucil was influenced by its availability and ease of administration in the clinical context. Conclusion: This archival report supports a pragmatic, context-sensitive approach to managing childhood steroid resistant nephrotic syndrome without immediate renal biopsy in selected cases. The observed clinical response to chlorambucil and the evidence of histologic variability in idiopathic nephrotic syndrome underscore the importance of individualized decision-making. While modern practices emphasize biopsy-guided therapy, revisiting historical strategies may offer valuable insights, especially in settings with limited resources.

Keywords: Steroid-Resistant Nephrotic Syndrome, Minimal Change Disease, Focal Segmental Glomerulosclerosis, Chlorambucil, Renal Biopsy, Pediatric Nephrology, Historical Perspective.