Growth hormone deficiency (GHD) in children leads to stunted growth and short stature, requiring daily subcutaneous recombinant human growth hormone (rhGH) administration. While rhGH therapy has a well-established efficacy and safety profile, it has been associated with renal complications, including glomerular hyperfiltration, renal hypertrophy, and glomerulosclerosis. However, the association between rhGH and acute kidney injury (AKI) remains unexplored. We report a 15-year-old male with a known history of GHD managed with daily somatropin therapy. The patient presented with a 4-day history of upper respiratory tract infection, vomiting, diarrhea, and bilateral flank pain after receiving non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics (cefixime and metronidazole). Initial creatinine levels were elevated at 2.8 mg/dL, rising to 4 mg/dL within days, without evidence of dehydration, proteinuria, or urinary casts. Extensive workup, including autoimmune panels (antineutrophil cytoplasmic antibodies (ANCA), antiphospholipid, complement levels), was unremarkable. A renal biopsy revealed significant vacuolization of tubular and podocyte cells without necrosis or inflammation. rhGH therapy was discontinued and the patient received pulse methylprednisolone therapy (500 mg IV for 3 days) followed by oral prednisolone. Renal function improved and the patient was discharged with stable creatinine and normal kidney function. This case highlights a potential link between rhGH therapy and AKI, suggesting that growth hormone may exacerbate tubular injury under certain conditions, such as infection and NSAID use. Further research is required to investigate the pathophysiology of rhGH-related kidney injury and identify at-risk populations.