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Chimeric Antigen Receptor T cell (CAR T) therapy has shown significant therapeutic potential but carries risk of treatment related toxicity. There is limited data describing risk of acute kidney injury (AKI) related to CAR T therapy. To identify the incidence of AKI and recovery of renal function in patients undergoing CAR T therapy. We analyzed adult patients given FDA approved CAR T cell therapy February 2018 to 2019 for Non-Hodgkin Lymphoma (NHL) at our center. Patients received axicabtagene ciloleucel (Yescarta®) (34/46, 74%) or tisagenlecleucel (Kymriah®) (12/46, 26%). All creatinine's prior to and following CAR T infusion until last follow up were collected. Maximum (max) grade AKI [grade 1 (creatinine 1.5 - < 2-fold baseline), grade 2 (2 - < 3-fold baseline) or grade 3 (> 3-fold baseline)] was calculated based on KDIGO criteria. Renal recovery was assessed using creatinine 30 days post max grade AKI. Forty six patients, median age 63 years (range 19-85) of whom 33 (72%) were men underwent CAR T therapy for relapsed/ refractory NHL. Patients had a median of 4 lines of chemotherapy (range 2-10) prior to CAR T, including autoSCT (n=9, 20%), alloHCT (n=3, 7%), and both auto and alloHCT (n=1). Lymphodepletion regimens were either cyclophosphamide/fludarabine (n=43, 93%) or bendamustine (n=3, 7%). Baseline co-morbidities were hypertension 13/46 (28%) and diabetes mellitus 1/46 (2%). Median baseline creatinine was 0.8 (range 0.5 – 2) mg/dL, and median glomerular filtration rate (GFR) was 88 [(range 36-160) mL/min/1.73m2, GFR ≤ 60 in 4 patients]. No patient was on dialysis prior to infusion. Five of 14 patients with baseline urinalysis had ≥30 mg/dL protein. Median overall follow up was 8.3 (95%CI: 6.8 - 11.4) months. Fourteen patients (30%) had any grade AKI during available follow-up. Of these, 10/14 (71%) had grade 1, 2/14 (14%) had grade 2, and 1/14 (7%) had grade 3. Median day onset for max grade AKI was 48 (range 6 to 100) days. Nephrotoxic medication exposures prior to AKI included acyclovir in 10 (71%), vancomycin in 11 (79%) and ibuprofen in 1 (7%). Of the 14 patients who developed AKI, 11 (79%) also had cytokine release syndrome (CRS). For these patients, median peak C reactive protein level was 12 (range 0.4 to 34) mg/L and median interleukin-6 level was 179 (range 14 to 23,752) pg/ml. After removing competing events (relapse, progression or death), cumulative incidence of grade 1 AKI was 15.2% (95% CI 4.7-25.7) and grade 2 AKI was 2.2% (95% CI 0-6.5) by day +100. Incidence of AKI shown in Figure 1. Creatinine returned to baseline in 11/12 (92%) patients alive at 30 days post AKI. Our study shows that the incidence of AKI is low in patients receiving CAR T therapy. Majority of AKI was grade 1 and returned to baseline within 30 days. A larger study sample will likely help elucidate risk factors associated with development of AKI in these patients. [ABSTRACT FROM AUTHOR]

Background: Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia.Study Design: We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide.Results: We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively.Conclusions: This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation. [ABSTRACT FROM AUTHOR]