Though no clear relationships have been found to date for the development of TMA after HSCT, a number of risk factors have been examined. In earlier studies, where HUS was the primary diagnosis, risk factors identified were total body irradiation (TBI) [
14,
15,
48,
49] and calcineurin inhibitor use [
15,
27,
50‐
54]. However, in more recent studies of TMA, acute graft-versus-host disease (GVHD) grades 2–4, older age, and transplant from an unrelated donor are the primary risk factors identified [
55,
56]. Other investigators identified sinusoidal obstruction syndrome, matched unrelated donors or haploidentical donors, and lymphoid malignancy as significant predictors of TMA after HSCT in addition to the above risk factors [
17,
57‐
59]. However, in children who develop HUS after HSCT, the presumptive risk factor in these studies was TBI used as part of the conditioning regimen. For example, Tarbell et al. studied 44 children (aged 3–15 years) with acute lymphocytic leukemia (ALL) or neuroblastoma (NB) who underwent HSCT [
14]. Twenty-nine of these patients were alive and in remission 3 months after HSCT and were evaluated in the study. Eleven patients developed increases in blood urea nitrogen (BUN) and creatinine, and ten were anemic and thrombocytopenic with evidence of hemolysis on peripheral blood smear; they also had elevated lactate dehydrogenase (LDH) levels. In every patient except one, the hemolytic process resolved, yet renal insufficiency persisted. The pathologic findings of mesangiolysis with intraglomerular capillary aneurysm formation in conjunction with laboratory abnormalities support the diagnosis of HUS in these children. In another small study, Antignac et al. described seven children referred to their nephrology clinic with CKD approximately 5–10 months after TBI followed by HSCT [
48]. All seven children had leukemia, and all received cyclophosphamide alone or with cytosine arabinoside and vepeside, in addition to single-dose TBI as part of their conditioning regimen. Three patients developed CKD without hypertension, and four developed HUS with severe hypertension and microangiopathic hemolytic anemia. Of these, two of the four had normalization of their renal function. Follow-up biopsies, however, showed extensive scarring of the renal parenchyma but almost complete resolution of the mesangiolysis. The glomeruli were globally sclerotic, ischemic, or demonstrated mesangial hypercellularity. Thus, there was evidence of persistent and progressive renal damage in these patients despite normalization of serum creatinine and urinalysis. The occurrence of two different clinical presentations, CKD without hypertension and HUS with hypertension, but similar pathology in these children supports the notion that this is a spectrum of disease rather than distinct pathophysiologic processes.