Combined pancreatic islet and kidney transplantation in a child with unstable type 1 diabetes and end-stage renal disease

Abstract

Islet transplantation after successful kidney transplantation is a recognized treatment for adults with diabetes and end-stage renal disease (ESRD), but has not been considered an option in the pediatric population. To our knowledge, we report the first combined islet and kidney transplant in a child. The patient was born with bilateral renal hypoplasia and was diagnosed with type 1 diabetes mellitus at age 13 months. He had erratic glycemic control and hypoglycemia unawareness. At 6 years of age, the child safely underwent simultaneous islet and live donor kidney transplantation. Although function of the islet graft was transient, the combined transplant provided significant benefits in terms of glucose control and overall growth and development. Such an approach represents a viable treatment option for pediatric patients with ESRD and unstable diabetes.

Keywords: Islet transplantation; kidney transplantation; pediatric; renal disease; type I diabetes.

Figure 1. Islet and kidney function after combined transplantation

The patient became insulin independent during months 5–7 after transplant and resumed full dose insulin use by 12 months. The bars represent stimulated c-peptide levels obtained during mixed meal tolerance tests performed at 3, 6, and 12 months post-transplant. Fasting c-peptide levels remained detectable through 12 months post-transplant but became undetectable (<0.1 ng/ml) by 15 months post-transplant.

Figure 2. Development of donor-specific antibodies after combined islet-kidney transplantation

Antibodies to the kidney (solid lines) and islet (dashed lines) donor HLA types are depicted. The increases in anti-islet antibodies correlated with loss of islet graft function. The increase in antibodies to DQ5 from the kidney donor seen at the same time points is most likely due to cross reactivity between anti-DQ5 and anti-DQ6 antibodies since DQ5 and DQ6 share many epitopes. Mean fluorescence intensity (MFI) level cutoffs at our institution are as follows: high risk: >8500; moderate risk: 2000–8499; low risk: 1000–1999.