A 16-year-old male patient with Down syndrome diagnosed with AKI and urinary tract infection was treated with meropenem for ESBL-positive E. coli in urine culture. Persistently elevated creatinine and persistent post-void residual (PVR) of >300 mL led to further testing, which revealed urethral stricture and a lower sacral Tarlov cyst. Due to no complete improvement with urethral dilatation, he underwent laminectomy and Tarlov cyst fenestration. Creatinine normalized, with increased urine output and robust flow. Due to a PVR of >100 mL, he received behavioral therapy, including sitting and timed voiding, and the PVR was reduced to <5 mL.