Kidney transplantation in children: Case

This girl has end-stage kidney disease from bilateral renal hypodysplasia, a congenital anomaly of the kidney and urinary tract and the leading cause of paediatric end-stage kidney disease leading to transplant. Her estimated glomerular filtration rate of 13 mL per minute per 1.73 square metres places her at the threshold where dialysis is imminent, so a preemptive living-donor transplant from her father is the optimal plan. This avoids dialysis entirely and offers the best long-term graft survival. [2]

Clinical findings

The clinical picture is that of advanced chronic kidney disease. Her growth failure, anaemia and hypertension are the systemic consequences of uraemia and reduced erythropoietin production. Renal hypodysplasia is a structural cause of kidney failure, so unlike glomerular disease there is no heavy proteinuria or nephritic syndrome to manage, and the disease will not recur in the graft because it is congenital and structural. This is a favourable feature, because it removes recurrent disease from the post-transplant differential. [1]

The choice of a preemptive living-related transplant is justified by two independent advantages. A living-donor kidney, especially from a parent, gives the best graft survival because the kidney is healthy and the cold ischaemia time is short. A preemptive transplant, performed before dialysis begins, avoids the growth failure, cardiovascular damage and infectious risk of dialysis and is itself associated with superior graft survival. 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 donor workup must already be complete. [2]

Transplant and immunosuppression

At the operation she receives induction with basiliximab, an interleukin-2 receptor antibody, because she is a low-immunological-risk recipient with a living-related graft and no sensitising antibodies. Her maintenance immunosuppression is the standard 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, which is minimised over the first months to protect her growth. [3]

Therapeutic drug monitoring of tacrolimus is central to her care because the drug has a narrow therapeutic window. Her trough whole-blood tacrolimus 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. She is started on co-trimoxazole prophylaxis against Pneumocystis jirovecii pneumonia. Because she received basiliximab rather than a lymphocyte-depleting agent, her opportunistic viral risk in the first months is lower than a highly sensitised recipient's, but she is still monitored for cytomegalovirus and Epstein-Barr virus by PCR. [4]

The rising creatinine: investigation and diagnosis

Three months after transplant, her creatinine rises from 78 to 135 micromoles per litre over one week. She is otherwise well, with no fever, no change in urine output, and a blood pressure of 118 over 76. Her tacrolimus trough is 16 ng per mL, above target. The differential diagnosis of a creatinine rise in a transplanted child is worked through systematically as pre-renal, intrinsic graft, and post-renal causes, with the five intrinsic causes being acute tubular necrosis, acute rejection, calcineurin inhibitor nephrotoxicity, recurrent disease and BK virus nephropathy. [5]

The investigation 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 ureteric obstruction 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. Because her underlying disease is structural hypodysplasia, recurrent disease is not expected, which narrows the differential to acute rejection, calcineurin inhibitor toxicity and BK nephropathy. [4]

The biopsy shows acute T-cell-mediated rejection with moderate tubulitis and interstitial inflammation, no C4d staining, and no features of calcineurin inhibitor toxicity. Her donor-specific antibodies are negative and her BK viral load is low. The diagnosis is acute T-cell-mediated rejection, likely triggered by a period of undertacrolimusaemia, since her level had drifted up and down around the target. [5]

Management and outcome

She is treated with high-dose intravenous methylprednisolone for three days, and her maintenance tacrolimus dose is adjusted to bring the trough back within target. Her creatinine falls to 92 micromoles per litre over the following week, confirming steroid-responsive rejection. Antithymocyte globulin was not required because she responded to steroids. The team reviews her adherence and her dosing schedule, and her family is counselled on the importance of taking the tacrolimus at consistent times on an empty stomach. [5]

The longer-term plan addresses the threats that will accumulate over the years of the graft. Her steroid is minimised to protect her growth, which accelerates after the transplant as the uraemia resolves. Her hypertension is managed with a calcium channel blocker. She is monitored for post-transplant diabetes, dyslipidaemia and chronic calcineurin inhibitor nephrotoxicity at every clinic visit. Donor-specific antibodies are checked periodically to detect subclinical antibody-mediated rejection, the leading cause of long-term graft loss. [2]

As she approaches adolescence, a structured transition programme begins. The team knows that non-adherence is the single most common cause of late graft loss in adolescents, and that graft loss clusters around the transfer to adult care. She is taught self-management, her mental health and body image are addressed, and a written summary with a warm handover is prepared for the adult nephrology team. The family is counselled that no graft lasts forever, and that most paediatric recipients will need at least one retransplant in their lifetime, so the aim is to maximise the years of function through adherence, monitoring and aggressive management of cardiovascular risk. [6]