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Clinical Features of AKI in the Early Post-Transplant Period Following Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation
Vergara-Cadavid, J., Johnson, P. C., Kim, H. T., Yi, A., Sise, M. E., Leaf, D. E., Hanna, P. E., Ho, V. T., Cutler, C. S., Antin, J. H., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplant (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). Few studies have examined risk factors for AKI at engraftment, or its relationship with clinical outcomes. OBJECTIVE The objective of this study was to examine the incidence and risk factors for peri-engraftment AKI, as well as the association between AKI and overall survival and non-relapse mortality. METHODS We conducted a retrospective analysis of adult patients receiving reduced intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Peri-engraftment (day 0 to day 30) AKI incidence and severity was defined using modified Kidney Disease: Improving Global Outcomes criteria. Factors associated with peri-engraftment AKI risk were examined using Cox regression analysis. The impact of peri-engraftment AKI on overall survival and non-relapse mortality (defined as death without recurrent disease after HCT), was evaluated using Cox regression and Fine and Gray's competing risk model, respectively. Kidney recovery, defined as a return of serum creatinine within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 in relation to HCT. RESULTS Peri-engraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days [IQR 4-30] post-transplant. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (HR: 1.56, 95% CI: 1.20-2.03; p<0.001), fludarabine/melphalan conditioning (HR: 1.35, 95% CI: 1.01-1.81; p=0.05; compared to fludarabine/busulfan and fludarabine, cyclophosphamide, total body irradiation), HCT-Comorbidity Index ≥4 (HR: 1.43, 95% CI: 1.14-1.79; p=0.002), albumin <3.4 g/dl (HR: 2.04, 95% CI: 1.33-3.12; p=0.001), hemoglobin ≤12 (HR 1.96, 95% CI 1.38-2.78; p<0.001), supratherapeutic tacrolimus (HR 1.45, 95% CI 1.07 - 1.95; p=0.02), and baseline serum creatinine >1.1 mg/dl (HR: 1.87, 95% CI: 1.48-2.35; p<0.001). Peri-engraftment AKI was associated with worse overall survival (HR 1.40, 95% CI: 1.16-1.71; p<0.001) and non-relapse mortality (subdistribution HR 2.10, 95% CI: 1.52-2.89; p<0.001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, 2, and 3 AKI without KRT, respectively, and 4 of 16 (25%) patients were liberated from KRT. CONCLUSION Peri-engraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for peri-engraftment AKI. Peri-engraftment AKI is associated with worse overall survival and non-relapse morality, highlighting the importance of timely recognition and management of AKI.
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Impact of antimicrobial drug-drug interactions on acute kidney injury after allogeneic hematopoietic cell transplantation
Wada, F., Arai, Y., Jo, T., Mizumoto, C., Kanda, J., Kitawaki, T., Nishikori, M., Yamashita, K., Takaori-Kondo, A.
Transplantation and cellular therapy. 2023
Abstract
Acute kidney injury (AKI) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Use of multiple antimicrobials is one of the major causes of post-transplant AKI, due the potential nephrotoxicity of each agent and drug-drug interactions (DDI). No satisfactory reports on DDI have appeared in the field of allo-HSCT, and we performed a retrospective analysis to compare the incidence of AKI within 100 days. In total, 465 transplant cases (416 patients) were included, and cumulative incidence of AKI was 40.0%. Incidence of AKI significantly reduced overall survival (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.95-3.55, p<0.01) and increased transplant-related mortality (HR 4.77, 95%CI 2.90-7.88, p<0.01). A higher incidence of AKI was significantly associated with the use of ciprofloxacin, cefepime, tazobactam/piperacillin, meropenem, vancomycin, liposomal amphotericin B, ganciclovir, and foscarnet. Among them, combinations with vancomycin plus tazobactam/piperacillin (HR 2.23. p=0.09 for interaction), ganciclovir plus cefepime (HR 5.93, p=0.04), and ganciclovir plus meropenem (HR 2.63, p=0.12) synergistically increased the risk of AKI, whereas combinations involving teicoplanin did not. This is the first report dealing with DDIs after allo-HSCT, and such combinations should be avoided so as to preserve renal function and to reduce AKI-related morbidity and mortality.
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Acute kidney injury in patients receiving high-dose etoposide phosphate as conditioning prior to hematopoietic stem cell transplantation in hematologic malignancies may be associated with elevated body mass index
Stewart, T., Dowling, M., Janson, B., Siderov, J., Xie, J., Grigg, A., Khot, A.
Leukemia & lymphoma. 2022;:1-3
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The use of low doses of methotrexate during peri-cell infusion period may be a risk factor for acute kidney injury in patients subjected to hematopoietic stem cell transplantation
Ferraz, F. T. P., Marra, A. R., Hamerschlak, N., de Souza Durao Junior, M.
Annals of hematology. 2020
Abstract
Acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) is associated with high mortality rates. To determine the incidence and risk factors associated with AKI in patients undergoing HSCT during the infusion period, patients admitted for HSCT from 2012 to 2015 were studied. AKI was classified according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria. We analyzed the main comorbidities, underlying conditions, types of transplant, preparative regimens, and use of potentially nephrotoxic drugs as risk factors for AKI. Among the 180 patients (median age 53 years), 69 (36.5%) developed AKI (23 KDIGO 1, 28 KDIGO 2, and 18 KDIGO 3), 49 (50.0%) undergoing allogeneic and 20 (22.3%) autologous transplantation, and 18 (9.4%) required dialysis. The main comorbidities were hypertension (38; 19.8%), and diabetes (19; 9.9%). The median pre-transplant creatinine was 0.7 mg/dl. Twenty-one patients died (10.9%). The risk factors for AKI in allogeneic HSCT were as follows: baseline estimated glomerular filtration rate (eGFR) (RR 1.12 (1.02-1.22), p = 0.019), use of vasopressors (RR 3.72 (2.20-6.29), p < 0.001), and use of methotrexate (RR 1.83 (1.08-3.11), p = 0.025). Male gender (RR 5.91 (1.65-21.16), p = 0.006), baseline eGFR (RR 1.22 (1.04-1.43), p = 0.011), and use of aminoglycosides (RR 3.92 (1.06-14.44), p = 0.041) were the risk factors for AKI associated with autologous HSCT. During hospitalization for HSCT, AKI was a common problem. The use of a low dose of methotrexate to prevent graft versus host disease was associated with its occurrence.
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Acute kidney injury after high dose etoposide phosphate: A retrospective study in children receiving an allogeneic hematopoetic stem cell transplantation
Barnoud, D., Pincon, C., Bruno, B., Bene, J., Gautier, S., Lahoche, A., Petitpain, N., Vasseur, M., Barthelemy, C., Decaudin, B., et al
Pediatric blood & cancer. 2018
Abstract
BACKGROUND Etoposide phosphate (EP; single injection, 60 mg/kg) followed by total body irradiation (TBI) at 12 Gy has been used as an allogeneic stem cell transplantation (allo-SCT) conditioning regimen for children since 2010. In our institution, EP has been suspected of leading to acute nephrotoxicity. The aim of this study was to assess the potential renal toxicity of EP in this context. MATERIALS AND METHODS A retrospective study was carried out on children hospitalized between 2007 and 2015 for allo-SCT with TBI-based myeloablative conditioning associated with cyclophosphamide (CY, 60 mg/kg/day x 2 days) or EP. The primary endpoint of the study was the occurrence of acute kidney injury (AKI). Additional endpoints were time to recovery for children with AKI, survival, and treatment-related mortality. RESULTS Thirty-five patients were analyzed (CY: 22 vs. EP: 13). AKI occurred more frequently in the EP group than in the CY one (69% vs. 27%, adjusted odds ratio 6.0, 95% confidence interval [CI] [1.145; 31.445], P = 0.03). The median time to recovery was estimated at 3 days, 95% CI (2; 17), with CY and 11 days 95% CI (5; 18) with EP (adjusted hazard ratio of recovery for EP vs. CY 0.262, 95% CI [0.071; 0.969], P = 0.04). No significant difference was highlighted between the two treatments for survival or for treatment-related mortality. DISCUSSION This study shows that EP at high dosage or one of its excipients is probably responsible for AKI, as compared to CY. Further studies are required to explore the origin of this adverse effect.