Incidence, Outcomes and Predictors of Acute Kidney Injury Post Allogeneic Stem Cell Transplant
Authors: Madsen Kayla , Cote Gabrielle , Pelletier Karyne , Kitchlu Abhijat , Chen Shiyi , Mattsson Jonas , Pasic Ivan 
Published: November 2020

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers cure for some patients with hematological diseases but is associated with significant risk of morbidity and mortality. Acute kidney injury (AKI) represents an important cause of post-transplant complications, often multifactorial in the unique setting of allo-HSCT. However, to date, there is limited information on the overall impact of AKI in this patient population. To address this, we retrospectively reviewed the effect of AKI on transplant outcomes at Princess Margaret Cancer Centre (PMCC).
METHODS: The study included 408 patients transplanted at PMCC between January 2015-January 2018 for any indication, using either reduced intensity (RIC) or myeloablative conditioning (MAC). Median follow-up time was 23 months. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Demographics, clinical characteristics and transplant related variables were extracted from patient records and the institutional allo-HSCT database. Univariate and multivariate Cox proportional hazard models were used to examine associations between AKI and outcomes including overall survival (OS), relapse free survival (RFS), graft versus host disease (GVHD) and relapse-free survival (GRFS). Univariate and multivariate Fine and Gray competing risk models were used to examine the association between AKI and incidence of relapse, treatment related mortality (TRM), grade 2-4 acute GVHD (aGVHD), grade 3-4 aGVHD and moderate-severe chronic GVHD (cGVHD). Multivariate models were used to examine the association of AKI and outcomes of interest, while adjusting for potential risk factors.
RESULTS: The overall incidence of AKI at 100 days was 64% (stage 1: 62.6%, stage 2: 22.5% and stage 3: 14.8%). Dialysis was required in 2% of these patients. Mean baseline eGFR in the AKI group was 94.4 mL/min/1.73m2 (IQR 42, 141) vs 96.9 mL/min/1.73m2 (IQR 45.7, 142.9) in the non-AKI group. Patient-related risk factors for development of AKI were age over 60 (p=0.001), male gender (p=0.05), diabetes (p=0.004) and hypertension (p=0.003). Transplant related characteristics associated with AKI were MAC conditioning (p=0.02), veno-occlusive disease (p&lt;0.0001), BK viremia (p=0.01), thrombotic microangiopathy (p=0.009), bacterial infections (p=0.001) and more than two cytomegalovirus (CMV) reactivations (p=0.02). There was no difference in mean cyclosporine levels in the first 100 days between patients who developed AKI and those who did not (p=0.80). AKI was less common in patients who received GVHD prophylaxis with dual T-cell depletion (TCD) with anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) (p&lt;0.001) than those who received alternative GVHD prophylaxis. In the univariate analyses, compared with patients who did not have AKI, those with AKI had inferior 2-y OS: 46% versus 63% (p=0.0004). AKI patients had lower 2-y GRFS (29% vs 45%, p=0.0002), higher 2-y TRM (31% versus 17%, p=0.0003), and higher incidence of day 100 grade 3-4 aGVHD (13% vs 6%, HR 2.18, 95% CI=1.18-4.01, p=0.01). In multivariate analysis, AKI was associated with decreased 2-y OS (HR= 1.36, 95% CI 1.00-1.65, p=0.048), 2-y GRFS (HR= 1.42, 95% CI 1.10-1.82, p=0.006), and increased risk of day 100 grade 3-4 aGVHD (HR= 1.93, 95% CI 1.04-3.58, p=0.03). There was an association between AKI and TRM, specifically in those patients with stage 2 (HR= 1.76, 95% CI 1.06-3.30, p=0.03) and stage 3 AKI (HR= 2.64, 95% CI 1.44-4.83, p=0.002) compared to no AKI. In multivariate models, there was no association between AKI and relapse (p=0.65), grade 2-4 aGVHD (p=0.7) or moderate-severe cGVHD (p=0.81).
CONCLUSION: Patients who develop AKI within 100 days of transplant have lower OS, GRFS, and higher grade 3-4 aGVHD and TRM. The use of dual TCD for GVHD prophylaxis is associated with lower risk of AKI, suggesting this may be a favorable regimen for those at increased risk for AKI. Contrary to previously published literature, there was no difference in cyclosporine levels between the non-AKI and AKI groups, suggesting that it may not be a significant cause of AKI post-transplant. AKI was more common in patients who had multiple episodes of CMV reactivation, highlighting the importance of CMV prophylaxis. AKI patients require close follow up, preventative strategies and monitoring for new or progression of chronic kidney disease post transplant.

Disclosures
Madsen: Jazz Pharmaceuticals: Honoraria. Pelletier:Celgene: Honoraria; International Kidney and Monoclonal Gammopathy: Membership on an entity's Board of Directors or advisory committees. Mattsson:Jazz Pharmaceuticals: Honoraria; ITB: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Honoraria; Gilead: Honoraria.