Differentiation Syndrome Presenting as Acute Kidney Injury in a Patient of Acute Promyelocytic Leukemia on All-trans Retinoic Acid and Arsenic Trioxide Regimen: A Case Report

Abstract

Acute promyelocytic leukemia (APL), classified as Subtype M3 of acute myeloid leukemia, is known for its relatively favorable prognosis, primarily due to the high effectiveness of all-trans retinoic acid (ATRA) in treating the maturation block. However, it is essential to be aware of potential complications such as ATRA syndrome, which can affect 5%–25% of patients and manifest with symptoms such as fever, interstitial pulmonary infiltration, pleural/pericardial effusion, and acute renal failure. We present the case of a 47-year-old female with a history of hypertension, who experienced rash, fever, and reduced urine output during the induction phase with ATRA. Her serum creatinine levels exhibited a rapid increase from 2.63 mg/dL on October 07, 2022, to 7 mg/dL on October 18, 2022, despite having normal-sized kidneys and normal corticomedullary differentiation. A renal biopsy conducted on October 20, 2022, revealed features consistent with active tubulointerstitial nephritis, with direct immunofluorescence showing no significant glomerular immune deposits. A total of 17 hemodialysis sessions were performed. A subsequent bone marrow examination conducted on October 26, 2022, demonstrated a hypercellular aspirate with normal morphology. However, due to the persistence of renal failure, a repeat biopsy was performed, revealing severe acute tubular injury. Pulse steroids were initiated, and ATRA was discontinued, resulting in an improvement in renal function. This case highlights an instance of acute, early, and severe differentiation syndrome (DS) occurring after induction therapy in a patient with APL. The DS in this case was particularly severe, leading to renal failure necessitating hemodialysis. The prompt initiation of pulse steroids and discontinuation of ATRA proved to be effective in managing this complication. Clinicians should remain vigilant for DS and its potential complications, including acute kidney injury and acute tubulointerstitial nephritis, when treating patients with APL.