Idiosyncratic drug reactions and membranous glomerulopathy

Area of Science:

• Pediatric Nephrology
• Clinical Pharmacology
• Immunology

Background:

• Steroid-resistant nephrotic syndrome (SRNS) often requires immunosuppressive therapy.
• Calcineurin inhibitors (CIs) such as ciclosporin and tacrolimus are used for SRNS management.
• Adverse drug reactions to CIs can be severe and complex.

Observation:

• An infant with idiopathic membranous glomerulonephropathy (IMPGN) achieved remission with ciclosporin but developed eosinophilia and hyper-IgE.
• Switching to tacrolimus led to eosinophilic gastroenteritis, muscle weakness, polyserositis, and failure-to-thrive.
• Discontinuation of tacrolimus and subsequent ciclosporin withdrawal resulted in complete clinical normalization.

Findings:

• In vitro studies showed decreased cell viability with both ciclosporin and tacrolimus exposure.
• These findings suggest a direct cytotoxic effect of CIs on the patient's cells.
• The patient experienced a relapse of IMPGN responsive to ciclosporin after tacrolimus withdrawal, but this was managed by discontinuing CIs.

Implications:

• This case highlights potential severe toxicities of calcineurin inhibitors in pediatric SRNS.
• It underscores the importance of careful monitoring and consideration of alternative therapies.
• In vitro cell viability assays may aid in predicting or understanding CI-related adverse events.