Kidney Transplant against the Odds: Overcoming ADAMTS13 Deficiency

Dear Editor, Acquired or congenital ADAMTS13 deficiency, a metalloproteinase that cleaves the von Willebrand factor may manifest as a multisystem disease involving the kidneys causing renal failure and end-stage kidney disease (ESKD).[1] Renal transplantation is considered the ideal mode of renal replacement therapy, especially in younger age group patients. Offering renal transplantation to ESKD patients with increased risk of microvascular thrombosis like ADAMTS13 deficiency brings several challenges into the picture, the most feared one being the risk of recurrence of the disease and imminent graft loss, especially in parts of the world where molecules like eculizumab are scarce and unaffordable.[2] Master X is a 13-year-old boy who had no previous illness, presented with fatigue, vomiting, and seizures, and on evaluation had severe anemia (hemoglobin – 5.9 g/dl), thrombocytopenia (1.13 × 106 µl), and renal failure. Peripheral smear showed the features of microangiopathic hemolytic anemia with a raised serum lactate dehydrogenase of 500 IU/L. Renal biopsy showed 5 out of 7 glomeruli sclerosed with severe interstitial fibrosis and tubular atrophy and negative immunofluorescence. He was treated with 6 cycles of plasma exchange and hemodialysis for acute renal failure. His workup for thrombotic microangiopathy showed low ADAMTS13 levels <6% with a normal ADAMTS13 inhibitor level. His complement factor H levels and anti-complement factor H antibody were normal. Whole-exome sequencing did not reveal any variants of genetic significance. His disease was considered probable congenital ADAMTS13 deficiency. With the progression of kidney disease, he was initiated on continuous ambulatory peritoneal dialysis. His father volunteered as a donor for renal transplantation, and immunological workup was unremarkable with a negative screen for human leukocyte antigen antibodies and a negative flow crossmatch. In order to tackle the inevitable microvascular thrombosis that could hamper allograft function, a plan of action was devised to keep the levels of ADAMTS13 levels up with careful transfusions of fresh frozen plasma (FFP). FFP regimen was started 3 days prior to surgery. He underwent renal transplantation surgery with no complication and received induction immunosuppression using Anti-thymocyte globulin (3 mg/kg) and he was started on maintenance immunosuppression using prednisolone, mycophenolate, and tacrolimus. He attained good graft function immediately after transplant. He was given 15ml/kg of FFP transfusion each on days 1, 3, 5, and 7 post transplantation followed by 15ml/kg of FFP twice a week in the 2nd week, once a week until the end of the 1st month, once in 2 weeks until 3 months and is planned to receive once per month FFP transfusions until 6 months [Figure 1]. His ADAMTS13 levels were monitored and were 51% at the end of the 1st month. He has normal allograft function with serum creatinine of 0.8 mg/dL, hemoglobin of 12 g%, and platelet count of 160,000 cells/µl.Figure 1: Fresh frozen plasma transfusion regimenPatients like Master X with ESKD due to thrombotic microangiopathy like ADAMTS13 are usually deemed poor candidates for renal transplantation due to the high risk of graft loss and often renal transplant is not considered an option. There have been few case reports of successful renal transplant in patients with ADAMTS13 deficiency managed with FFP therapy.[3] This letter is to highlight the effectiveness of FFP in facilitating renal transplantation in patients with ADAMTS13 deficiency and attaining good allograft function. Declaration of patient consent The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.