Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia.

BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported. METHODS: The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. We conducted a retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution. RESULTS: There was a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n = 7), with four cases being severe AKI (stages 2-3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14 days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30 days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and cytokine release syndrome and neurotoxicity. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe. CONCLUSIONS: Frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population.

Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent and young adult patients with B-cell acute lymphoblastic leukemia.

CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. Treatment with CD19-CAR T-cell therapy is also associated with the risk of morbidity and mortality, primarily related to immune-mediated complications (cytokine release syndrome [CRS] and neurotoxicity [NTX]), infections, and end-organ dysfunction. Despite these well-described systemic toxicities, the incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent and young adult (CAYA) patient population is largely unreported. The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. In this retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution, we found a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n=7), with 4 cases being severe AKI (Stage 2-3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14 days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30 days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and CRS and NTX. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe. Although most patients with AKI in our cohort had recovery of kidney function, frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population.

Elucidation of Renal Scars in Children With Vesicoureteral Reflux Using Contrast-Enhanced Ultrasound: A Pilot Study.

INTRODUCTION: Vesicoureteral reflux is a common disorder in children but can result in kidney scarring following acute pyelonephritis. The gold standard diagnostic to detect renal scars in children is 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. DMSA has a number of limitations including radiation exposure, need for sedation, and radiotracer supply shortages. Contrast-enhanced ultrasound (CEUS) is a technique whereby biocompatible microspheres of inert gas are administered i.v. that reflect ultrasonography sound waves and do not involve radiation. Because the contrast agent is rapidly cleared, contrast images must be obtained within minutes of administration. CEUS has been used in a variety of organ systems, but its use in pediatric kidney diseases is limited. METHODS: In this study, we performed CEUS in 7 children with documented renal scars by radiographic imaging consistent with reflux nephropathy. RESULTS: In all subjects, CEUS detected all previously known radiologic abnormalities as well as detecting new areas of hypoenhancing renal parenchyma. None of the patients experienced any serious adverse events. DISCUSSION: This study represents the first report of using CEUS to characterize renal scars in children with reflux nephropathy. We conclude that CEUS is a highly sensitive, rapid, and cost-effective diagnostic imaging modality for detecting and monitoring renal scars in children with vesicoureteral reflux.

Comprehensive renal function evaluation in patients treated for synchronous bilateral Wilms tumor.

OBJECTIVES: The purpose of this study was to perform a comprehensive assessment of long-term renal function in patients treated at our institution for synchronous bilateral Wilms tumor (BWT) and to determine the optimal method for estimating glomerular filtration rate (eGFR). METHODS: Surgical approach, adjuvant therapy, and pathology reports were reviewed for patients with at least six months follow-up from definitive surgery. eGFRs, as assessed by the Schwartz and Chronic Kidney Disease in Children (CKiD) formulas, were compared to measured GFR (mGFR) determined by 99mTc-DTPA scanning. Urine studies, including microalbumin, ß-microglobulin, and FENa were also reviewed. RESULTS: Forty-two patients were identified. Of 36 living patients, 28 (77.8%) had greater than 6months follow-up, with a median overall follow-up of 5.2years (range: 1.4-13.4). The median mGFR was 97mL/min/1.73m2, while the median eGFRSchwartz and eGFRCKiD were 103.3mL/min/1.73m2 and 79.7mL/min/1.73m2, respectively, (p=0.13 and p=0.75, compared to mGFR). Eleven (39.3%) patients had at least one abnormal urine study (microalbumin >30µg/g creatinine, n=3; ß-2 microglobulin >133µg/g creatinine, n=9; FENa>1%, n=4). CONCLUSIONS: In our series, few patients had an abnormally low GFR. Neither method for estimating GFR gave a significantly different result from measured GFR, suggesting that the Schwartz equation is adequate, although specific urine tests may be more sensitive for detecting subtle renal dysfunction. LEVEL OF EVIDENCE: Level IV - retrospective case series with no comparison group.