Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review

Abstract

Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients.

Peer Review #3 of "Incidence of acute kidney disease after receiving hematopoietic stem cell transplantation: a single-center retrospective study (v0.2)"

“…Second, diabetes which could exacerbate renal function was recognized only 9 cases (8.3%) in our study. Third, as previously indicated, early involvement of the nephrologist in our case might prevent incidence of AKD [10,13]. Induction of combination therapy cyclosporine or tacrolimus, calcineurin inhibitors Manuscript to be reviewed (CNIs) and methotrexate could be superior to calcineurin inhibitors alone in the prophylaxis of acute GVHD.…”

Sequential transplantation and implications for clinical management: OLT followed by HCT and consequent RT in a pediatric patient

“…While incidence of CKD is variably defined, the incidence of ESRD is even more poorly defined, due to rarity and reliance on case reports . Known risk factors include conditioning (especially those containing TBI), exposure to CNIs, exposure to nephrotoxic anti‐infective agents during the post‐HCT time frame, and other complications such as development of GVHD . Similar to studies in the post‐SOT population, there has been most notable decline of renal function in the first year post‐HCT, with relative stabilization of renal function following .…”

“…The mechanism behind CNI toxicity is felt to be multifactorial, acutely causing renin‐angiotensin system activation and vasoconstriction of renal arterioles leading to acute damage that may be reversible . There is a known chronic component of declining renal function leading to progressive and irreversible glomerulosclerosis . These agents can independently predispose patients to hypertension, which can induce nephrotoxicity in its own mechanism.…”

“…33 There is a known chronic component of declining renal function leading to progressive and irreversible glomerulosclerosis. 5,30,33,34 These agents can independently predispose patients to hypertension, which can induce nephrotoxicity in its own mechanism. This case highlights the importance of routine monitoring for nephrotoxicity in all SOT patients.…”

Bone Marrow Derived Mesenchymal Stem Cell Therapy in Induced Acute Renal Injury in Adult Male Albino Rats

“…The Peri-tubular dilatation and congestion observed in the untreated group; showed improvement after local infusion of MSCs and completely disappeared after their systemic infusion. This was explained with the pro-angiogenic ability of MSCs and their ability to induce five folds increase in the level of vascular endothelial cell growth factors (VEGF) when administrated to the mice with acute renal ischemia [32,33]. MSCs can induce angiogenesis by supporting the new vasculature and maintain renal perfusion or by producing growth factors associated with the angiogenesis process as vascular endothelial growth factor (VEGF) insulin-like growth factor (IGF), and plateletderived growth factor (PDGF) [29].…”