Diabetic and Hypertensive Nephropathy Masquerading as Ifosfamide Nephrotoxicity in a Young Patient: A Case Report

Introduction: Ifosfamide-induced nephrotoxicity is a rare but recognized complication caused by proximal tubular damage. While drug toxicity is often the presumed culprit in young oncology patients with kidney dysfunction, alternate causes should be considered. We report a complex case of renal dysfunction following ifosfamide administration in a young adult, initially attributed to chemotherapy. However, subsequent evaluation—including kidney biopsy—revealed diabetic and hypertensive nephropathy, a rare finding in this age group. Case Description: A 22-year-old Asian male with a history of hypertension and prediabetic nephropathy was diagnosed with mesenchymal metastatic chondrosarcoma of the right femur with pulmonary metastases. His treatment included surgical resection followed by chemotherapy with the VAI regimen (vincristine, doxorubicin, and ifosfamide). After initiating the fifth cycle of ifosfamide, he presented with signs of acute kidney injury (AKI). His serum creatinine rose from a baseline of 1.1–1.3 mg/dL to 1.8–1.9 mg/dL, eventually peaking at 2.2 mg/dL. Initial workup showed hyperglycemia, intermittent hypertension, proteinuria >300 mg/dL, metabolic acidosis, and significant glycosuria on urinalysis. Losartan was discontinued due to worsening renal function and the AKI was attributed to ifosfamide-induced nephrotoxicity. However, given his decline despite management, a kidney biopsy was performed. Histopathology revealed acute tubular necrosis and features of chronic hypertensive and diabetic nephropathy, including arterionephrosclerosis, glomerular basement membrane thickening, and focal segmental glomerulosclerosis (FSGS) in 32% of glomeruli (22/68). There was no evidence of immune complex or paraprotein deposition, though interstitial fibrosis and tubular atrophy were noted. His antihypertensive regimen was optimized with hydralazine and amlodipine. The patient continues radiation and chemotherapy, and his AKI has since resolved. Discussion: While diabetic and hypertensive nephropathy are uncommon causes of AKI in young adults, this case highlights the importance of considering underlying CKD even in patients on nephrotoxic agents. Kidney biopsy was crucial in distinguishing true chemotherapy-induced toxicity from preexisting pathology. Early tissue diagnosis can guide chemotherapy planning and dosing to prevent further renal injury.