Desensitization protocols should be considered for children with positive crossmatches awaiting renal transplantation. Children are sensitized usually due to previous renal (and/or other solid-organ) transplants but can be from administration of blood and/or platelet transfusions, infections, and immunizations (as sensitization from pregnancy is a rare occurrence in pediatric patients). However, the definition of HLA-incompatible (HLAi) renal transplantation in the literature varies and is best considered only when there is a positive cross-match (positive baseline flow cytometric cross-match or positive complement-dependent cytotoxic cross-match). Renal transplantation where the recipient has donor-specific antibodies (DSA) but a negative cross-match should not fall into this category, although they are higher risk.