Kidney Week

Abstract: PUB195

Recognizing and Managing Severe AKI Due to Acute Promyelocytic Leukemia-Associated Differentiation Syndrome: A Case Report

Session Information

• Publication Only

Category: Onconephrology

• 1600 Onconephrology

Authors

• Chughtai, Ahmad, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Ahmad Chughtai, MD

• Le, Cindy, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Cindy Le, MD

• Aamir, Nawal, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Nawal Aamir, MD

• Choi, Moonyoung, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Moonyoung Choi, MD

• Ralto, Kenneth M., University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Kenneth M. Ralto, MD, FASN

Introduction

Acute promyelocytic leukemia (APML) is a hematologic emergency that may be complicated by acute kidney injury (AKI), leading to significant clinical consequences. Differentiation syndrome (DS), a known complication of treatment with all-trans retinoic acid (ATRA), can result in multiorgan failure and carries substantial morbidity. We present a case of APML complicated by severe DS, manifesting as acute respiratory distress syndrome (ARDS), refractory volume overload, and AKI requiring continuous kidney replacement therapy (CKRT).

Case Description

A 76-year-old woman with asthma, hypertension, and bioprosthetic aortic valve presented with 2 weeks of progressive fatigue, exertional dyspnea, and weight loss. Laboratory evaluation revealed hemoglobin 5.8 g/dL, platelets 13,000/µL, and 82% blasts on peripheral smear. Empiric ATRA therapy was initiated due to suspicion for APML, later confirmed by FISH positive for PML-RARA (t15;17). Within 1 week of ATRA initiation, she developed progressive hypoxemia, diffuse ground glass opacities on chest CT, leukocytosis, and a 10-lb weight gain. Laboratory evaluation showed rising inflammatory markers (ESR, CRP) and serum creatinine increased from 1.1 to 2.1 mg/dL, concerning for ATRA-induced DS. The patient was treated with high-dose intravenous dexamethasone and aggressive diuresis, however respiratory decline continued. CKRT was started for refractory fluid overload and metabolic stabilization. Despite optimized ARDS management and ultrafiltration, the patient’s condition continued to deteriorate, and the patient was transitioned to comfort focused care.

Discussion

Differentiation syndrome represents a hyperinflammatory state triggered by ATRA-induced maturation of leukemic promyelocytes and cytokine release (IL-1β, IL-6, TNF-α, VEGF). Endothelial activation leads to capillary leak, interstitial edema, and multiorgan dysfunction, primarily affecting the lungs and kidneys. Acute renal injury arises from hemodynamic instability, cytokine-mediated endothelial injury, and third spacing from capillary leak, compounding volume overload and hypoxemia. This case highlights the importance of early nephrology involvement, immediate corticosteroid escalation, and interruption or dose adjustment of ATRA in DS to prevent progression to ARDS and end-organ failure.