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Rupesh Raina,1– 3 Ahmad Houry,1,3 Pratik Rath,1 Guneive Mangat,1 Davinder Pandher,1,4 Muhammad Islam,3 Ala’a Grace Khattab,3 Joseph K Kalout,1 Sumedha Bagga5 1Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA; 2Department of Nephrology, Akron Children’s Hospital, Akron, OH, USA; 3College of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA; 4Mount Sinai South Nassau, Oceanside, NY, 11570, USA; 5Questrom School of Business, Boston University, Boston, MA, USACorrespondence: Rupesh Raina, Consultant Nephrologist, Adult-Pediatric Kidney Disease/Hypertension, Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA, Tel +1 330-543-8950, Fax +1 330-543-3980, Email rraina@akronchildrens.org; raina@akronnephrology.comAbstract: Autosomal dominant polycystic kidney disease, also known as ADPKD, is the most common hereditary kidney disease, affecting different age groups. ADPKD can eventually lead to end-stage renal disease. The etiology of ADPKD is genetic, resulting in the formation of cysts containing fluids on the kidneys. Patients with ADPKD present a range of symptoms following a decline in kidney function. Pain, stones, proteinuria and osteoporosis are few of the many symptoms, resulting from decreased kidney function. Tolvaptan, a selective V2 receptor antagonist, is the etiological treatment used for ADPKD. In this paper, we conducted a systematic review of the literature between 2011 and 2021 to gather data regarding the tolerability and efficacy of tolvaptan use in ADPKD. A total of 22 trials were reviewed. Tolvaptan efficacy in the trials was measured using changes in eGFR or changes in total kidney volume. Results showed that tolvaptan use in ADPKD was associated with a slower decline in kidney function and a decrease in total kidney volume. Side effects of this drug include polyuria, nocturia and polydipsia along with hepatotoxicity. The two biggest trials, TEMPO and REPRISE, change in eGFR from pre-treatment baseline to post-treatment was 1.3 mL/min/1.73 for REPRISE and 1 mL/min/1.73 for TEMPO 3:4. A mean decrease of 49% in total kidney volume from baseline to post-treatment was found in the TEMPO 3:4 study.Keywords: ADPKD, tolvaptan