A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function by administration of gentamicin. Renal artery embolization was performed in five Dutch white goats by infusing polyvinyl alcohol particles in branches of the renal artery, aiming for the embolization of ~80% of one kidney and complete embolization of the contralateral kidney. Gentamicin was administered to temporarily further increase the plasma concentrations of uremic toxins. After initial acute kidney injury, urea and creatinine plasma concentrations stabilized 1.5 ± 0.7 months post-embolization and remained elevated (12 ± 1.4 vs. 5.6 ± 0.8 mmol/L and 174 ± 45 vs. 65 ± 5.6 µmol/L, resp.) during follow-up (16 ± 6 months). Gentamicin induced temporary acute-on-chronic kidney injury with a variable increase in plasma concentrations of small solutes (urea 29 ± 15 mmol/L, creatinine 841 ± 584 µmol/L, phosphate 2.2 ± 0.3 mmol/L and potassium 5.0 ± 0.6 mmol/L) and protein-bound uremic toxins representative of patients with ESKD. A uremic goat model characterized by stable moderate uremia was established via subtotal renal artery embolization with the induction of temporary severe acute-on-chronic kidney injury by the administration of gentamicin, allowing preclinical in vivo validation of novel renal replacement technologies.