Autosomal dominant polycystic kidney disease, ADPKD, is a family disease. It is passed from one parent to a child, it fills the kidneys with fluid-filled cysts over decades, and for most of medical history there was nothing to do about it but wait. That changed in 2018, and Southeastern Clinical Research Institute, the research arm of Nephrology Associates, was part of the trial that changed it.
The disease
ADPKD affects 1 in every 400 to 1,000 people and is the most common kidney disorder passed down through families.1 Because it is autosomal dominant, a person needs the gene change from only one parent, and each child of an affected parent has a one-in-two chance of inheriting it. Most people with ADPKD carry a change in the PKD1 gene; about 1 in 6 or 1 in 7 carry a change in PKD2, which tends to run a slower course.1
The cysts grow slowly and silently. In many cases ADPKD causes no signs or symptoms until cysts are half an inch or larger, by which point the kidneys may already be enlarged.1 Most people with ADPKD have pain, high blood pressure, and kidney failure at some point in their lives; liver cysts, kidney stones, urinary tract infections, and brain aneurysms are the other complications a nephrologist watches for.1 More than half of people with ADPKD progress to kidney failure by age 70.1
- 1 in 400 to 1 in 1,000 people have ADPKD, the most common inherited kidney disease.1
- 50% chance each child of an affected parent inherits it.
- Over half reach kidney failure by age 70.1
Diagnosis and the measure that matters
ADPKD is diagnosed by imaging, ultrasound, CT, or MRI, and confirmed by genetic testing when the picture is unclear or a family is planning.1 In research, the number that tracks the disease is total kidney volume, usually adjusted for height (htTKV): kidneys that are growing fast are kidneys that will fail sooner, and a therapy that slows that growth is a therapy worth testing. It is the endpoint SCRI's investigators have measured across three ADPKD programs.4
The first treatment, and the trial behind it
On April 24, 2018, the U.S. Food and Drug Administration approved tolvaptan (JYNARQUE®) as the first treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD.2 Two trials carried the approval. In the three-year TEMPO 3:4 study in earlier-stage disease, tolvaptan slowed the yearly loss of kidney function by about 1.0 mL/min/1.73 m² compared with placebo. In the one-year REPRISE study in later-stage disease, the decline was 2.3 mL/min/1.73 m² per year on tolvaptan against 3.6 on placebo, a treatment effect of 1.3.2
REPRISE ran at Southeastern Clinical Research Institute.3 Augusta patients helped establish that the drug still works once the kidneys are already losing function, which is the population most nephrologists actually see. Tolvaptan is dispensed under a restricted program because of a risk of liver injury, and it requires liver-enzyme monitoring; that is one reason it is prescribed by nephrologists who know the drug.2
What comes next
Tolvaptan slows ADPKD; it does not stop it. The next generation of therapy aims at the mechanism of cyst growth itself. One approach silences microRNA-17, a molecule that is over-active in ADPKD kidneys and drives cyst formation. SCRI was a site for the Phase 1b study of RGLS8429, now called farabursen, in adults with ADPKD, measuring safety, disease biomarkers, and height-adjusted total kidney volume.4,5 That program has since moved toward late-stage trials under Novartis, which acquired Regulus Therapeutics in 2025.
Augusta's part in it
Three ADPKD programs have been completed at SCRI: the pivotal REPRISE trial, its long-term tolvaptan safety extension, and the first-in-class anti-miR-17 Phase 1b.3,4,5 The investigators are the same board-certified nephrologists, led by Dr. Matthew Diamond, DO, FASN, FACP, who see ADPKD families in clinic at Nephrology Associates, which is why those families were already under their care when the protocols opened.
For families living with ADPKD
If ADPKD runs in your family, the most useful things you can do are also the simplest: get imaged if you have not been, keep your blood pressure controlled, and see a nephrologist early rather than at kidney failure. Ask about tolvaptan if your disease is progressing quickly, and ask us about research. There is no cost to take part in a study at SCRI, your own doctor stays involved, and the same physicians who ran REPRISE are the ones who will talk with you.
Ask if a study fits you · Refer a patient · Book an appointment
Sources
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Autosomal Dominant Polycystic Kidney Disease.
- Otsuka Pharmaceutical, news release, April 25, 2018. JYNARQUE™ (tolvaptan) approved by U.S. FDA as the first treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD; efficacy figures from the TEMPO 3:4 and REPRISE trials as reported there.
- ClinicalTrials.gov, NCT02160145. Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to ADPKD (REPRISE). Site list includes Augusta, Georgia.
- Southeastern Clinical Research Institute. Site research experience: completed clinical trials, including Otsuka 156-13-210 and 156-13-211 and Regulus RGLS8429-02.
- ClinicalTrials.gov, NCT05521191. A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease. Sponsor: Regulus Therapeutics. Site list includes Augusta, Georgia.
This article is general health and research information from a clinical research institute. It is not medical advice and does not replace a conversation with your physician.