Acute Renal Failure after Nonmyeloablative Hematopoietic Cell Transplantation

Abstract

Abstract. Acute renal failure (ARF) is a common life-threatening complication after myeloablative allogeneic hematopoietic cell transplantation (HCT). Nonmyeloablative HCT aims to eradicate the malignancy with graft-versus-tumor effect, rather than with high doses of chemoradiotherapy. It may be anticipated that a lower risk of ARF exists in nonmyeloablative HCT as a result of the milder preconditioning regimen. However, the patients who receive the nonmyeloablative HCT are older individuals who are not eligible for the more toxic allogeneic myeloablative procedure. The goal of this study was to evaluate ARF in a large group of patients who received nonmyeloablative HCT. This cohort study enrolled patients who were undergoing nonmyeloablative HCT at four major centers from 1998 to 2001. Conditioning therapy involved total body irradiation 2 Gy Ϯ fludarabine 30 mg/m 2 . Posttransplantation immunosuppression consisted of cyclosporine or tacrolimus and mycophenolate mofetil. ARF was classified into four grades, similar to previous studies in the literature. Collectively, 253 patients were recruited into this study. ARF (Ͼ50% decrease in GFR) occurred in 40.4% of patients over a 3-mo period, with 4.4% of patients requiring dialysis. The overall mortality in the study population was 34% at 1 yr. The mortality increased with worsening grade of ARF. The combined need for dialysis and artificial ventilation was associated with a mortality exceeding 80%. Although the number of patients who develop ARF is significant, the risk of developing ARF that requires dialysis after nonmyeloablative HCT is infrequent despite the older age of the patients. The data are also suggestive that ARF may contribute to mortality after nonmyeloablative HCT.Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for a variety of malignant and immunologic hematologic diseases. Myeloablative (conventional) allogeneic HCT involves the use of high-dose chemotherapy and radiotherapy conditioning regimens to eradicate the underlying disease, and the allograft serves to rescue the patient from pancytopenia induced by the treatment. One of the major limitations of this approach is the high degree of acute toxicity associated with the myeloablative conditioning regimens. This toxicity has restricted the use of myeloablative allogeneic HCT to younger, healthier patients (1,2). However, the majority of patients who present with hematologic malignancies that might be cured with myeloablative allogeneic HCT are older than the typically recommended upper age limit for this procedure of 50 to 55 yr.Despite advances in supportive care, transplant-related morbidity and mortality remain a significant obstacle to achieving maximal benefits that can be obtained from HCT. Transplantrelated organ dysfunction is a major contributor to transplantrelated complications. Specifically among these, acute renal failure (ARF) occurs frequently after both autologous and conventional allogeneic HCT. It has been demonstrated that ARF is a ...

A multicenter, retrospective study of acute kidney injury in adult patients with nonmyeloablative hematopoietic SCT

“…22 In this study, the mortality rate of patients within 1 year was found to be 27.4%, which was lower than that reported earlier. 5,8 Therefore, we suggested that nonmyeloablative HSCT might be a safe therapy for younger patients and for elderly patients without baseline organ dysfunction.…”

“…These factors may act solely or collectively to cause renal failure. 7,8 aGVHD may affect the kidney through cytokine-and immune-related injury, including glomerular deposits, leading to nephrotic syndrome and tubulitis. 21 However, other studies showed that dehydration because of diarrhea in patients with aGVHD II-IV is most likely to be the cause of AKI.…”

“…Moreover, ARF is also an indicator of decreased survival. [7][8][9] Recently, several investigators have shown that small changes in kidney function in hospitalized patients are important and have an impact on outcome. [10][11][12] Subsequently, the terminology of ARF has been shifted to acute kidney injury (AKI).…”

Acute kidney injury in HCT: an update

“…70,74,77,78 Mortality rates are often elevated in the most severe form of TA-TMA, 72 whereas milder cases present an increased risk for CKD. 66 As in the general population, diabetes mellitus, 32 previous hypertension, 26 previous renal impairment, 79 sepsis, 13 amphotericin use, 80 requirement for mechanical ventilation 33 and admission to the intensive care unit 26 were all associated with increased risk for AKI following HCT. In actual fact, pre-HCT comorbidities greatly impact the outcome of patients undergoing HCT.…”

“…The major culprit for AKI in nonmyeloablative HCT is calcineurin inhibitors injury by themselves or in association with other etiologies, namely sepsis, nephrotoxicity or GVHD. 12,32,33 In both myeloablative allogeneic and nonmyeloablative HCT, calcineurin inhibitors are employed as prophylaxis against GVHD. One of the most common and serious complications associated with calcineurin inhibitors is their nephrotoxicity, manifested as AKI (mostly reversible after dose reduction) or as progressive CKD (usually irreversible).…”