Kidney transplantation in children: SAQ

This boy has end-stage kidney disease from congenital renal hypodysplasia, a leading cause of paediatric transplant, and is approaching dialysis. A preemptive living-donor transplant from his mother is the optimal plan because it offers superior graft survival and avoids the morbidity of dialysis entirely. The estimated glomerular filtration rate of 12 mL per minute per 1.73 square metres places him at the threshold where dialysis is imminent, so the donor workup should already be complete. ^[2]

Question 1 (10 marks)

Outline the rationale for a preemptive living-donor transplant, the standard maintenance immunosuppression regimen, and the role of therapeutic drug monitoring. ^[3]

The rationale for a preemptive living-donor transplant rests on two independent advantages. First, a living-donor kidney, especially from a parent, gives the best long-term graft survival because the kidney is healthy, the surgery is elective, and the cold ischaemia time is short. Second, performing the transplant before dialysis begins avoids the growth failure, neurodevelopmental harm, cardiovascular damage and infectious risk that dialysis itself causes, and graft survival after a preemptive transplant is superior to that after a dialysis-first transplant. The practical trigger is the eGFR: once it approaches 10 to 15 mL per minute per 1.73 square metres, dialysis is imminent, so the living donor should be worked up in advance so the child never starts dialysis. ^[2]

The standard maintenance immunosuppression is a three-drug regimen: tacrolimus, a calcineurin inhibitor that blocks T-cell activation by suppressing interleukin-2 transcription; mycophenolate mofetil, an antimetabolite that inhibits lymphocyte proliferation; and low-dose prednisolone, a corticosteroid that is minimised and, in selected low-risk recipients, withdrawn to protect growth. Induction at the operation uses basiliximab for a low-risk recipient such as this boy, or a lymphocyte-depleting agent such as antithymocyte globulin for a sensitised or higher-risk recipient. ^[3]

Therapeutic drug monitoring of tacrolimus is essential because tacrolimus has a narrow therapeutic window. The trough whole-blood level is kept around 5 to 10 nanograms per millilitre in the early post-transplant period, then lowered to a long-term target to limit chronic nephrotoxicity. The level is affected by drug interactions: azole antifungals and macrolide antibiotics inhibit cytochrome P450 3A4 and raise the level toward toxicity, while rifampicin, phenytoin and St John's wort induce the enzyme and lower the level toward rejection. The level is therefore checked frequently and the dose adjusted to the result rather than to a fixed prescription. ^[4]