Nephrotoxicity of Cyclosporin a after Allogeneic Marrow Transplantation

Shulman, HM; Striker, Gary E.; Deeg, H. Joachim; Kennedy, Michael S.; Storb, Rainer; Ed, Thomas

doi:10.1056/nejm198112033052306

Cited by 354 publications

(112 citation statements)

References 8 publications

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“…On histologic examination of kidneys from three HCT patients who were on cyclosporine and died with renal failure, thrombus formation was observed in capillary tufts and arterioles with subendothelial and mesangial widening and sclerosis. Conversely, none of 55 patients who were not on cyclosporine had renal capillary or arteriolar thromboses (55). Cyclosporine also is a potent vasoconstrictor of the afferent arteriole of the glomerulus.…”

Section: Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Pumentioning

confidence: 96%

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

Hingorani

2006

Journal of the American Society of Nephrology

130

111

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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...

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Section: Thrombotic Microangiopathies: Thrombotic Thrombocytopenic Pumentioning

confidence: 96%

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

Hingorani

2006

Journal of the American Society of Nephrology

130

111

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“…1,8 While cyclosporin is most often implicated as the cause of this syndrome in bone marrow and in solid organ transplant recipients, 4,9 a number of other risk factors have also been described. The observation that TA-TMA may occur in autologous blood stem cell transplant recipients suggests that high-dose chemotherapy alone may be responsible for some cases of this disorder.…”

Section: Incidence and Risk Factors For Ta-tmamentioning

confidence: 99%

Transplantation-associated thrombotic microangiopathy: twenty-two years later

Daly

Xenocostas

Lipton

2002

Bone Marrow Transplant

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Summary:A syndrome of microangiopathic hemolytic anemia, renal dysfunction and neurological abnormalities was first noted in bone marrow transplant recipients 22 years ago. Now known as transplantation-associated thrombotic microangiopathy (TA-TMA) to distinguish it from other thrombotic microangiopathies, this disorder responds poorly to conventional treatments for thrombotic thrombocytopenic purpura. In this review, we discuss the incidence and risk factors for TA-TMA and describe a pathophysiologic model of the disorder based on results obtained from laboratory models of the thrombotic microangiopathies. We conclude by suggesting possible approaches to the early diagnosis and treatment of TA-TMA based on this model that may warrant testing in future clinical trials.

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“…17 for review) has been found in up to 25% of transplanted adults and may progress to end-stage renal disease with a poor outcome in terms of survival on dialysis. Some renal injury syndromes are probably related to CyA, especially a hemolytic-uremic-like syndrome as firstly described by Shulman et al 18 Radiation, cyclosporin A therapy, late effects of cytostatic treatment and graftversus-host disease are potential risk factors especially for renal tubular dysfunction and the development of ifosfamide-induced nephrotoxicity is well characterized. 19 It is also well-known that renal Fanconi syndrome may occur months or even years after the end of chemotherapy.…”

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confidence: 99%

Renal function in long-term survivors of stem cell transplantation in childhood. A prospective trial

Patzer

Ringelmann

Kentouche

et al. 2001

Bone Marrow Transplant

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Summary:The aim of this prospective study was to assess glomerular and tubular renal function before, and 1 and 2 years after hematological stem cell therapy (HSCT) in children and adolescents. 137 consecutive patients undergoing HSCT, for malignant diseases, were included in a prospective trial. Forty-four patients were followed for up to 1 year after HSCT and 36 for up to 2 years, without relapse. Ninety healthy school children were used as a control group. The following parameters were investigated: inulin clearance (GFR), urinary excretion of albumin, ␣ 1 -microglobulin (␣ 1 -MG), calcium, ␤-Nacetylglucosaminidase (␤-NAG) and Tamm-Horsfall protein (THP), tubular phosphate reabsorption (TP/Cl cr ) and percent reabsorption of amino acids (TAA). Significantly lower GFR was found 1 and 2 years after HSCT but within the normal range in the period before HSCT. There was no correlation between GFR within the first month after HSCT and long-term outcome of GFR. Tubular dysfunction was found in 14-45% of patients 1 and 2 years after HSCT depending on the parameter investigated. Pathological values 1 and 2 years after HSCT were found for ␣ 1 -MG excretion in 40% and 39%, respectively, for TP/Cl cr in 44% and 45%, for ␤-NAG in 26% and 19%. Median TP/Cl cr was significantly lower 2 years after HSCT than before. TAA was mildly impaired in 7/14 patients before, in 5/29 one and in 9/29 2 years after HSCT, but median TAA was within normal range at all times. The median excretion of albumin, THP and calcium was within the normal range at all investigations. No influence of ifosfamide pre-treatment on the severity of tubulopathy was found. The investigation of tubular renal function should be part of a long-term follow-up in children after HSCT. Bone Marrow Transplantation (2001) 27, 319-327.

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Nephrotoxicity of Cyclosporin a after Allogeneic Marrow Transplantation

Cited by 354 publications

References 8 publications

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

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

Transplantation-associated thrombotic microangiopathy: twenty-two years later

Renal function in long-term survivors of stem cell transplantation in childhood. A prospective trial

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