Thiopurine shunting in a renal transplant recipient: prepregnancy considerations with azathioprine and allopurinol

PMID: 40675654
Source: BMJ Case Rep
Publication date: 2025-07-24
Year: 2025

Abstract

Fertility and reproductive counselling are integral for female kidney transplant recipients. Although classified as high-risk, successful pregnancies in this group are increasingly reported. Immunosuppressive therapy, azathioprine and calcineurin inhibitors, is crucial for preventing graft rejection and safe during pregnancy. However, azathioprine metabolism can vary, leading to the production of metabolites, such as 6-thioguanine nucleotides and 6-methylmercaptopurine (6-MMP). We report a renal transplant recipient with hepatotoxicity from excessive 6-MMP production, despite normal thiopurine S-methyltransferase activity-suggesting thiopurine shunting. This metabolic imbalance was effectively managed by the addition of allopurinol, resulting in improved liver function tests. While this strategy is established in inflammatory bowel disease, its use in renal transplantation is rare, and evidence in pregnancy remains limited. This case highlights the importance of azathioprine metabolite monitoring in renal transplant patients, enabling recognition of thiopurine shunting and safe continuation of azathioprine with allopurinol cotherapy during preconception.