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• The incidence of acute kidney injury following chimeric antigen receptor T cell (CAR-T) cell therapy is low. • Previous hematopoietic cell transplantation, intensive care unit admission, and grade 3-4 cytokine release syndrome after CAR-T therapy may increase the risk of acute kidney injury (AKI). • Most patients who experience AKI after CAR-T therapy recover kidney function. Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5- to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline. CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy. The overall incidence of CRS was 78.3% (95% confidence interval [CI], 66% to 90.5%), of whom 13% (95% CI, 3.3% to 22.8%) developed grade 3-4 CRS, whereas the overall incidence of ICANS was lower at 45.7% (95% CI, 3.1% to 60.3%). The cumulative incidence of any grade AKI by day 100 was 30% (95% CI, 16.9% to 43.9%), with a grade 1 AKI incidence of 21.7% (95% CI, 9.7% to 33.8%) and a grade 2-3 AKI incidence of 8.7% (95% CI,.4% to 17%). No patients developed severe AKI necessitating renal replacement therapy. Patients with previous autologous or allogeneic stem cell transplantation, those requiring intensive care unit level care and with grade 3-4 CRS had a higher incidence of AKI. Most patients recovered, with kidney function returning to baseline within 30 days. We conclude that with early recognition and management of CAR-T complications, the incidence of AKI is low, the severity of injury is mild, and most patients recover kidney function within 30 days. [ABSTRACT FROM AUTHOR]

• Day 100 grade 2 to 3 acute kidney injury (AKI) incidence is high after adult cord blood transplantation. • Grade 1 to 2 AKI can be present with a normal creatinine. • A higher pretransplant serum albumin protects against AKI. • Critical illness and nephrotoxic drugs increase AKI risk. • Early post-transplant AKI increases 2-year chronic kidney disease risk. Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to <2-fold; grade 2, 2 to <3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years [range, 23-65], 114/153 [75%] acute leukemia, 27/153 [18%] African, 88/153 [58%] cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 [range, 0-9], median pretransplant albumin 4.0 g/dL [range, 2.6-5.2]) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval [CI], 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34+ cells, low day –7 albumin, critical illness/intensive care admission, and nephrotoxic drug exposure (predominantly CSA and/or foscarnet) were associated with AKI. In a day 100 landmark analysis, 6% of patients with no prior AKI had chronic kidney disease (CKD) at 2 years versus 43% with prior grade 1 and 38% with prior grade 2-3 AKI (overall P =.02). Adult CBT recipients are at significant AKI risk, and AKI is associated with increased risk of CKD. Prevention strategies, early recognition, and prompt intervention are critical to mitigate kidney injury. [ABSTRACT FROM AUTHOR]

Introduction While adult double unit CBT (dCBT) has disease-free survival comparable to that of HLA-matched adult donor allografts, frequent patient (pt) comorbidities combined with chemotherapy/TBI & cyclosporine-A (CSA) contribute to AKI risk. Using KDIGO criteria, we analyzed renal injury incidence & risk factors in adults undergoing dCBT. Methods Adult dCBT pts transplanted 2006-2016 for hematologic malignancies using Cy/ Flu/ Thio/ TBI 400 cGy & CSA (therapeutic range 250-450)/ MMF were analyzed. Using day 0 - 100 creatinines, maximum grade (gr.) AKI [gr. 1 (1.5 - < 2-fold baseline), gr. 2 (2 - < 3-fold baseline) or gr. 3 (> 3-fold baseline)] was calculated. If pts had multiple episodes, the highest grade was analyzed. The 2-yr CKD incidence (> 90 days of GFR < 60 & persisting until 2 years post-transplant) was calculated according to max. grade day 0-100 AKI. Results 153 pts [median 51 years (range 23-65), 114/153 (75%) acute leukemia, 27/153 (18%) African, 88/153 (58%) CMV seropositive] were transplanted. No patient had chronic kidney disease pre-dCBT; 32/153 (21%) had hypertension & 12/153 (8%) were diabetic. Median aaHCT-CI was 3 (range 0-9) with 92/153 (60%) pts having a score > 3. 34 (22%) pts had High-Very High rDRI diagnoses. Median pre-dCBT albumin was 4 (range 2.6 - 5.2). 96% of pts engrafted, 76% had grade II-IV acute GVHD by day 100 & 90% were alive & disease-free at day 100 (11 TRM, 3 relapse). 127 pts had AKI (45 gr. 1, 60 gr. 2, & 22 gr. 3) for a day 100 grade 1-3 AKI cumulative incidence of 83% (95%CI: 77-89) (median onset 40 days, range 0-96) & 54% (95%CI: 46-62) for gr. 2-3 AKI (median onset 43 days, range 0-96) (Figure 1). The mean of the 3-day mean CSA level preceding AKI onset was high at 360 ng/ml. African ancestry, CMV seropositivity & low day -7 albumin level & post-dCBT variables of ICU admission, nephrotoxic drug exposure & bacteremia were associated with gr. 1-3 AKI (Table 1A). In multivariate analysis, low day -7 albumin, ICU admission & nephrotoxic drugs were significant (Table 1B). With a median 40 months (range 12-125) survivor follow-up, 34/109 (31%) evaluable pts had CKD at 2-yrs with 1 pt requiring long-term dialysis. Grade 2-3 AKI prior to day 100 was associated with a higher likelihood of having CKD at 2-yrs: 38% vs 25% (Figure 2). Conclusion dCBT recipients are at significant risk for AKI which increases the likelihood of long-term CKD. Early recognition of impending AKI & prompt intervention is critical to mitigate severe kidney injury & long-term impairment. Prevention strategies include adequate hydration, tight CSA level control & substitution of non-nephrotoxic medications (e.g. Letermovir CMV prophylaxis instead of pre-emptive foscarnet, non-aminoglycosides antibiotics, azoles rather than amphotericin, PO cidofovir instead of IV). Investigation of novel GVHD prophylaxis that could permit lower CSA dosing & early AKI detection using biomarkers should also be investigated. [ABSTRACT FROM AUTHOR]

The reported incidence of acute kidney injury (AKI) after allogeneic hematopoietic cell transplantation (allo-HCT) varies from 10 to 73%. The association between GVHD, calcineurin inhibitors (CNIs) and risk for kidney injury remains controversial. We sought to describe the incidence of AKI and identify modifiable risk factors in large cohort of patients undergoing allo-HCT in our institution. All consecutive patients undergoing allo-HCT from 2014 to 2017 in our institution were included. Pre-HCT variables including patient and graft characteristics, as well as post-HCT variables, including nephrotoxic medication exposure, ICU admission, and CNI levels were analyzed in association with AKI. AKI was defined using KDIGO criteria, grades 1, 2 and 3, through post-transplant day 100. Severe AKI was defined as grades 2 or 3. Differences across groups were assessed using either Wilcoxon rank-sum tests or Fisher's exact tests. AKI risk factors were estimated using cause-specific Cox proportional hazards regression. A total of 616 patients underwent allo-HCT during the study period. Median age was 58 (19-79) years, 59% male, 83% Caucasian. Indication for HCT was leukemia in 49%, myelodysplastic syndrome in 16%, and lymphoma in 17%. Median baseline creatinine was 0.8 (0.3-2.7) mg/dL. Median age-adjusted HCT-comorbidity index was 3 (range 0-9). Median baseline albumin was 3.5 (IQR 3.3-3.8) mg/dL and BMI 27.2 (IQR 23.8-30.8). Incidence of acute GVHD was 47%, and 60 patients had severe (grades 3-4) GVHD. Bacteremia occurred in 19% of patients. Amphotericin preceded max-grade AKI in 3.1%, cidofovir in 0.8%, and Foscarnet in 4.4% of patients. Median tacrolimus level preceding AKI was 7.88 (range 4.2-23.2) mg/dL. By day 100 post-HCT, 403 (65.4%) had any AKI, 220 (35.7%) patients had grade 1 AKI, 119 (19.3%) grade 2 AKI, and 64 (10.4%) grade 3 AKI; 19 (3.1%) required hemodialysis. Median time to AKI was 17 (IQR 8-35) days, and median time to max-grade AKI was 31 (IQR 13-53) days. Ex vivo CD34-selected HCT patients had a lower risk for AKI, hazard ratio 0.46 (0.35-0.62), p<0.001 (Table 1). AKI in patients undergoing allo-HCT remains a major concern, affecting 65.4% of patients, with grade 2 and 3 AKI occurring in 19.3% and 10.4%, respectively. Patients receiving CNIs including tacrolimus have a significantly higher risk for AKI, whereas patients undergoing CD34-selected allo-HCT have a lower risk of AKI. The effect of AKI after HCT on long-term kidney function requires further prospective study. [ABSTRACT FROM AUTHOR]