Kidney transplantation in children: Viva

Branch 1: Rationale for preemptive living-donor transplant

The candidate should state that kidney transplantation is the treatment of choice over lifelong dialysis for a child with end-stage kidney disease because it improves survival, growth, quality of life and neurodevelopment. A strong candidate should explain that two factors independently predict superior graft survival: a living-donor kidney and a preemptive transplant performed before dialysis begins. The living-donor kidney, especially from a parent, survives longest because the kidney is healthy, the surgery is elective and the cold ischaemia time is short. A preemptive transplant avoids the morbidity of dialysis itself. [2]

If the examiner asks when to plan the transplant, the candidate should state that a preemptive transplant should be planned once the estimated glomerular filtration rate approaches 10 to 15 mL per minute per 1.73 square metres, because at that point dialysis is imminent. The living donor workup must be complete before dialysis is needed so the child never starts dialysis. This girl, with an eGFR of 13, is exactly at that threshold, so her father's donor workup should be expedited. [2]

Branch 2: Maintenance immunosuppression and therapeutic drug monitoring

If asked about the immunosuppression regimen, the candidate should describe the three-drug maintenance standard: tacrolimus, mycophenolate mofetil, and low-dose prednisolone. The candidate should explain the mechanism of each: tacrolimus is a calcineurin inhibitor that blocks T-cell activation by suppressing interleukin-2 transcription; mycophenolate is an antimetabolite that inhibits lymphocyte proliferation; the corticosteroid dampens the broader inflammatory response and is minimised or withdrawn in selected low-risk recipients to protect growth. Induction at the operation uses basiliximab for a low-risk recipient or a lymphocyte-depleting agent such as antithymocyte globulin for a higher-risk recipient. [3]

If the examiner probes therapeutic drug monitoring, the candidate should explain that tacrolimus has a narrow therapeutic window and requires trough-level monitoring. The trough whole-blood level is kept around 5 to 10 nanograms per millilitre in the early post-transplant period, then lowered long-term to limit chronic nephrotoxicity. The candidate should cite the key drug interactions: azole antifungals and macrolide antibiotics raise the level by inhibiting cytochrome P450 3A4, while rifampicin, phenytoin and St John's wort lower it by inducing the enzyme. A new prescription in a transplant recipient must always be checked for interactions. [4]

Branch 3: Investigating a rising creatinine

If the examiner introduces a creatinine rise three months after transplant, the candidate should take a systematic approach dividing the causes into pre-renal, intrinsic graft and post-renal. Pre-renal causes include volume depletion. Intrinsic graft causes include acute tubular necrosis, acute rejection, calcineurin inhibitor nephrotoxicity, recurrent disease and BK virus nephropathy. Post-renal causes include ureteric obstruction. The candidate should state that the five causes to work through every time prevent the error of assuming every creatinine rise is rejection. [5]

The investigation plan begins with serum creatinine and trend, electrolytes, full blood count, urinalysis and urine protein-to-creatinine ratio, and a repeat tacrolimus trough. A graft ultrasound with Doppler excludes obstruction, a collection and vascular thrombosis. Donor-specific antibodies and a BK virus blood PCR are sent. The definitive test is a graft biopsy read against the Banff classification, which distinguishes T-cell-mediated rejection (tubulitis, intimal arteritis), antibody-mediated rejection (microvascular inflammation, C4d positivity), calcineurin inhibitor toxicity (arteriolar hyalinosis, striped fibrosis) and BK nephropathy (SV40-positive tubulointerstitial inflammation). [4]

Branch 4: Distinguishing rejection, toxicity and BK nephropathy

If the examiner asks how the management differs, the candidate should state that the treatment of calcineurin inhibitor toxicity is to reduce the tacrolimus dose, whereas the treatment of acute T-cell-mediated rejection is to increase immunosuppression with high-dose intravenous methylprednisolone, adding antithymocyte globulin if it is steroid-resistant. Treating the wrong diagnosis causes harm. Antibody-mediated rejection is treated with plasmapheresis, intravenous immunoglobulin and rituximab, with bortezomib for refractory disease. [5]

A strong candidate should highlight the BK virus trap: BK virus nephropathy mimics acute rejection clinically and histologically, but the treatment is the opposite, namely to reduce immunosuppression so the child's own immunity controls the virus. The discriminators are the BK viral load in the blood and the SV40 stain on biopsy. The candidate should close by emphasising adherence, which is the commonest cause of late rejection and graft loss, and the need for lifelong nephrology follow-up with a structured transition to adult care. [6]