Chronic Kidney Disease in Long-Term Survivors of Hematopoietic Cell Transplantation

Abstract

High-dose myeloablative hematopoietic cell transplantation is becoming an increasingly common treatment modality for a variety of diseases. Patient survival may be limited by substantial treatment-related toxicities, including chronic kidney disease (CKD). Although the majority of CKD after transplantation is idiopathic, thrombotic microangiopathic syndromes and nephrotic syndrome have been described. Epidemiology, pathogenesis, and potential treatment options for the various clinical syndromes that are associated with CKD in hematopoietic cell transplantation patients is reviewed. As the indications for and the numbers of transplants that are performed worldwide increases, so will the burden of CKD. The nephrologists and oncologists will have to work together to identify patients who are at risk for CKD early to prevent its development and progression to end-stage kidney disease. 17: 199517: -200517: , 200617: . doi: 10.1681 H igh-dose myeloablative therapy followed by hematopoietic cell transplantation (HCT) is an increasingly common treatment for many malignancies and some genetic disorders. Approximately 20,000 HCTs now are performed annually worldwide and offer the prospect of cures for otherwise fatal or incurable diseases. The indications and applications for HCT are growing; for example, HCT now is considered for treatment of autoimmune diseases, Crohn's disease, and vasculitides that are refractory to other therapies (1,2). However, patient survival may be limited by substantial treatment-related toxicities. J Am Soc NephrolThis review focuses on chronic kidney disease (CKD) in survivors of HCT. For the nephrology consultant who deals with transplant survivors, it is important to be aware of the specific type of transplant and its complications to determine how best to treat the patient with renal injury secondary to thrombotic microangiopathy (TMA) syndromes, nephrotic syndrome (NS), persistent acute renal failure (ARF), and idiopathic CKD. Technique of HCTEach type of transplant carries its own risks and toxicities (Table 1). Autologous transplants involve the harvesting of a patient's own bone marrow or peripheral blood stem cells before high-dose myeloablative therapy, followed by re-infusion. Allogeneic transplants use bone marrow or peripheral blood stem cells from family members (ideally, HLA-matched siblings) or HLAmatched unrelated donors or stem cells from umbilical cord blood.Syngeneic transplants are from an identical twin donor. The infusion of stem cells is preceded by either myeloablative therapy (usually a combination of chemotherapy drugs or chemotherapy plus total body irradiation [TBI]) or nonmyeloablative (but immunosuppressive) therapy that allows host hematopoietic cells to coexist with donor stem cells to achieve mixed hematopoietic cell chimerism. The components of both myeloablative and nonmyeloablative conditioning regimens vary from center to center. The most common myeloablative regimens are cyclophosphamide plus TBI 10 to 14 Gy, busulfan plus cyclophosphamide, and busulf...

Renal pathology in hematopoietic cell transplantation recipients

“…[1][2][3] In the acute setting, renal failure may be due to renal toxicity of medications (chemotherapeutic, antibiotic, or immunosuppressive), tumor lysis syndrome, renal ischemia (including hypovolemia, veno-occlusive disease, etc), sepsis, infection (bacterial, fungal, or viral), or effects of radiation. [4][5][6] A hemolytic-uremia-like syndrome, often referred to as bone marrow transplant nephropathy, may manifest later (3-6 months or post-transplantation later), and classically shows histopathologic features of thrombotic microangiopathy with endothelial injury. [4][5][6][7] Although exposure of kidneys to radiation during hematopoietic cell transplantation has been hypothesized as a risk factor for bone marrow transplant nephropathy, studies have shown conflicting data regarding renal shielding and long-term renal insufficiency.…”

“…[4][5][6] A hemolytic-uremia-like syndrome, often referred to as bone marrow transplant nephropathy, may manifest later (3-6 months or post-transplantation later), and classically shows histopathologic features of thrombotic microangiopathy with endothelial injury. [4][5][6][7] Although exposure of kidneys to radiation during hematopoietic cell transplantation has been hypothesized as a risk factor for bone marrow transplant nephropathy, studies have shown conflicting data regarding renal shielding and long-term renal insufficiency. 5,[8][9][10][11][12] Other causes of thrombotic microangiopathy must be considered in hematopoietic cell transplant recipients, including exacerbation of endothelial injury by chemotherapy, immune-mediated injury, and perhaps most notably, cyclosporine inhibitor toxicity, given as prophylaxis or treatment for graft-versus-host disease.…”

“…[4][5][6][14][15][16] Although most studies in the literature have focused on glomerulonephritis in hematopoietic cell transplant recipients, tubulointerstitial and vascular pathology is not uncommon. 5 We report the pathologic findings and corresponding clinical data, treatment, and outcome in a series of consecutive renal biopsy specimens in hematopoietic cell transplantation patients from two institutions, including the first cases of membranous glomerulonephritis post autologous stem cell transplantation documented with immunofluorescence and ultrastructural studies.…”

An autopsy case that manifested no convincing histological changes of severe renal failure after hematopoietic stem cell transplantation

“…Transplanted patients experience various kidney diseases throughout the clinical course following HSCT [1,2]. Among them, acute kidney injury (AKI) develops in the early phase of HSCT and represents one of the most critical complications, as it largely governs the fate of the patients [3][4][5][6].…”

Pharmacogenomic associations in ABCB1 and CYP3A5 with acute kidney injury and chronic kidney disease after myeloablative hematopoietic cell transplantation

“…1 Renal disease is a major complication post-HCT with acute kidney injury (AKI) and chronic kidney disease (CKD) significantly contributing to nonrelapse mortality in these patients. 2,3 The genesis of renal disease after myeloablative allogeneic HCT is multifactorial and the identification of risk factors for both AKI and CKD is critical to allow for preventive measures. We have identified previously several risk factors including sinusoidal obstruction syndrome (SOS), amphotericin use and baseline serum creatinine.…”