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END-STAGE KIDNEY DISEASE (ESKD) IN CHILDREN

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Definition: Sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 (chronic kidney disease or CKD stage 5), requiring either dialysis or kidney transplantation (renal replacement therapy).

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Causes: Causes of CKD/ESKD in children differ vastly from those in adults. Hypertension and diabetes mellitus, although common causes of ESKD in adults, are exceedingly rare as causes in children. The most common causes of CKD/ESKD in children are:

  • Congenital renal anomalies (57%): Obstructive uropathy (21%), renal aplasia/hypoplasia/dysplasia (18%), reflux nephropathy (8%), polycystic kidney disease (4%)

  • Glomerular disease (17%—but 45% of patients >12 yr): Focal segmental glomerulosclerosis (FSGS) most common

  • Other (25%): Unknown; hemolytic uremic syndrome (HUS); genetic disorders (cystinosis, oxalosis, Alport's syndrome); interstitial nephritis1

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Kidney transplantation is preferred over dialysis as treatment for ESKD in children, as the risk for death is more than four times higher on dialysis than after kidney transplantation.2

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TYPES OF KIDNEY TRANSPLANTATION

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Preemptive kidney transplantation: “Preemptive” denotes a kidney transplant performed before a patient requires initiation of dialysis therapy. These transplants result in superior long-term outcomes compared to transplants done after starting dialysis.3 Preemptive transplants can be done with either living or deceased donor kidney grafts. This approach is not possible or recommended for some conditions (e.g., conditions requiring pretransplant nephrectomies, such as persistent nephrotic syndrome, chronic severe pyelonephritis, and malignant renovascular hypertension).

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Note: Patients receiving preemptive kidney transplants, by definition, still have adequate urine output via their native kidneys. This makes using urine output by itself as a marker of transplant graft function postoperatively problematic.

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Deceased donor kidney transplantation: The organ is obtained by accruing waiting time on the deceased donor/cadaver kidney list. Highly sensitized patients or those listed for multiple organs are given preference on the list. There is also a pediatric advantage for those listed before turning 18 years old.

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Living donor kidney transplantation: Related or unrelated living donors donate one kidney after a thorough medical and psychological evaluation process. Living donor transplants in general demonstrate superior long-term outcomes compared to deceased donor kidney transplantation.

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CONTRAINDICATIONS TO KIDNEY TRANSPLANTATION

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Contraindications to kidney transplant include sepsis, uncontrolled malignancies, irreversible multisystem organ failure not correctable by transplant, and severe cardiac or pulmonary disease that can't be cured by multiorgan transplant. Active underlying disease (e.g., systemic lupus erythematosus [SLE] or anti-GBM antibody disease) is also a contraindication for transplantation.

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IMMUNOSUPPRESSION IN PEDIATRIC KIDNEY TRANSPLANT

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INDUCTION THERAPY

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  • Purpose: To prevent T-cell activation in the perioperative period, when risk of acute rejection is highest.

  • *IL-2 receptor antibodies/antagonists (basiliximab): Used for most standard-risk first transplant recipients in our center.

  • Alemtuzumab (anti-CD52 monoclonal antibody): Depletes T and B lymphocytes, monocytes, natural killer cells. Used for second transplants, higher immunological risk recipients in our center, but ...

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