Cisplatin-induced acute kidney injury in lupus-prone NZB/W F1 mice: a potential experimental model of acute kidney injury superimposed on chronic kidney disease

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease frequently complicated by immune complex-mediated glomerulonephritis that can progress to chronic kidney disease (CKD). Acute kidney injury (AKI) superimposed on CKD (AKI on CKD) is associated with a markedly poor prognosis; however, experimental models that accurately reflect this condition in SLE are limited. This study aimed to establish and characterize an AKI on CKD model using SLE-prone mice with pre-existing immune complex-mediated glomerulonephritis. Female NZB/W F1 mice with established glomerulonephritis at 32 weeks of age were administered cisplatin (10 mg/kg, intraperitoneally) to induce AKI. Blood urea nitrogen (BUN), serum neutrophil gelatinase-associated lipocalin (NGAL), urinary NGAL, and the urinary NGAL-to-creatinine ratio were evaluated as clinicopathological indicators of renal injury. Following cisplatin administration, BUN and serum NGAL concentrations increased significantly. Urinary NGAL concentrations and the urinary NGAL-to-creatinine ratio were also significantly elevated on days 1-4 after AKI induction compared with baseline, whereas urinary protein concentration, urinary creatinine concentration, and the urinary protein-to-creatinine ratio showed no significant changes. NGAL is synthesized by macrophages, glial cells, and epithelial cells under inflammatory conditions and is an established biomarker of tubular injury in AKI. The observed increases in BUN and NGAL parameters confirm successful induction of AKI in SLE mice with pre-existing CKD. This cisplatin-induced AKI model in NZB/W F1 mice may serve as a useful AKI on CKD model for investigating disease mechanisms and developing therapeutic strategies for AKI in patients with SLE and CKD.