Autosomal dominant polycystic kidney disease (ADPKD) – one of the leading causes of end-stage renal disease (ESRD) – is associated with various extrarenal manifestations. Timely intervention is crucial for slowing renal function decline in rapid progressors. At the Hong Kong Medical Forum (HKMF) 2026, Professor Yong-Chul Kim from the Division of Nephrology, Seoul National University Hospital, South Korea, shared his country’s approach to patient education in ADPKD and discussed the role of tolvaptan, a vasopressin V2- receptor antagonist, in disease management, highlighting evidence from clinical trials and real-world studies.
Impact of Korean PKD Society Group
National kidney organizations and patient support groups play an important role in raising ADPKD awareness and providing patients with relevant information. [Kidney Int 2025;107(2S):S1-S239]
“The PKD Society Group under the Korean Society of Nephrology has driven sustained academic exchange and patient engagement since 2021. We have extensive patient education campaigns including a dedicated YouTube channel, as well as patient education classes for ADPKD patients and their families that have been successfully implemented across 22 major hospitals, reaching nearly 1,000 participants,” shared Kim. “We also published ADPKD patient casebooks covering specific real-life questions regarding water intake, pregnancy and genetics, which help to alleviate patients’ anxiety.”
“These efforts, together with improved access to treatment through enhanced insurance coverage, have contributed to increased use in South Korea, with the number of ADPKD patients receiving tolvaptan increasing by about 20 percent between 2022 and 2023,” highlighted Kim.
Tolvaptan in ADPKD: Benefits and considerations
The 2025 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend initiation of tolvaptan in adult ADPKD patients with an estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m² who are at risk of rapid disease progression, as indicated by Mayo Imaging Classification class 1C to 1E or a historical eGFR decline of ≥3 mL/min/1.73 m²/year. [Kidney Int 2025;107(2S):S1-S239]
Long-term treatment with tolvaptan in ADPKD brings multiple benefits, including reducing eGFR decline by 1.3 mL/min/1.73 m²/year, slowing the increase in total kidney volume (TKV) with the greatest effect seen in the first year of treatment, and reducing acute pain events such as renal stones and urinary tract infections. In practice, these benefits require careful balancing against potential harms, including aquaretic adverse events (AEs) such as polyuria, the risk of drug-induced hepatotoxicity (mitigated with lifelong liver function monitoring), as well as drug interactions and the cost of treatment. To minimize and manage aquaretic AEs effectively, thorough counselling should be provided, with emphasis on maintaining access to water. Dose adjustment and increased fluid intake may be required if dehydration occurs, and special care should be taken in patients at risk of water loss, such as those with vomiting or diarrhoea. [Kidney Int 2025;107: S1-S239]
Given the potential risks, identifying patients most likely to benefit from tolvaptan is critical. “ADPKD typically shows a prolonged period of preserved kidney function within the normal range due to compensatory hyperfiltration in surviving glomeruli, followed by accelerated eGFR decline later in the disease course. Therefore, early identification of rapid progressors, who are likely to benefit from treatment, is essential for timely intervention,” said Kim. The Mayo Imaging Classification stratifies patients into classes 1C to 1E as rapid progressors based on their height-adjusted TKV (htTKV) annual pecentage increase (class 1C: 3–4.5 percent; 1D: 4.5–6 percent; 1E: >6.0 percent). [Kidney Int 2015;88:17-27; J Am Soc Nephrol 2015;26:160-172]
Tolvaptan in early and later-stage ADPKD
Tolvaptan’s renal benefits in early-stage ADPKD were demonstrated in the phase III TEMPO 3:4 trial. Compared with placebo, tolvaptan significantly (p<0.001) slowed kidney enlargement by reducing rate of TKV increase by 49.2 percent/ year, and also slowed renal function decline by 31.6 percent/year as measured by reciprocal serum creatinine level (-2.61 vs -3.81 [mg/mL]-¹/year; p<0.001). In terms of safety, 8.3 percent of patients in the tolvaptan group discontinued treatment because of aquaresis-related AEs. Two patients experienced concurrent elevations in alanine aminotransferase or aspartate aminotransferase and bilirubin, both of which resolved either during treatment or after treatment discontinuation, with no long-term sequelae reported. [N Engl J Med 2012;367:2407-2418; Clin J Am Soc Nephrol 2016;11:803-811]
In the REPRISE trial, which enrolled patients with later-stage ADPKD, tolvaptan slowed eGFR decline by 1.27 mL/ min/1.73 m² over a 1-year period compared with placebo (95 percent confidence interval, 0.86–1.68; p<0.001). Extrapolation of the trial results indicated that initiating tolvaptan at a baseline eGFR of 60 mL/min/1.73 m² could delay time to ESRD by up to 6.8 years, with greater effect expected if treatment is initiated earlier in the course of the disease. (Figure) [N Engl J Med 2017;377:1930-1942; J Am Soc Nephrol 2018;29:2458-2470]
Real-world evidence of tolvaptan
Beyond clinical trials, the Korean multicentre, single-arm, open-label phase IV ESSENTIAL trial (n=117) provided evidence on the efficacy and safety of tolvaptan in rapidly progressing ADPKD in real-world settings. At week 4, compared with baseline, eGFR decreased by 6.4 ± 7.9 mL/min/1.73 m² and htTKV decreased by 16 ± 45 mL/m, along with significant patient-reported improvement in dull pain severity (p=0.003), highlighting its short-term effects. In the long term, average TKV growth rate was 4.5 ± 0.5 percent among patients with available TKV measurements up to 24 months, with the greatest attenuation of kidney growth observed at the completion of titration. While higher incidence of hepatic AEs was observed compared with previous studies, they resolved after drug discontinuation. Meticulous titration and regular monitoring both support safe and effective use of tolvaptan in ADPKD. [Kidney Res Clin Pract 2026;45:220-231; Kidney Res Clin Pract 2023;42:216-228]
Use of tolvaptan in older patients
Tolvaptan use in patients aged >55 years with rapid progression requires individualized, shared decision-making due to age-related comorbidities such as vascular disease. However, age alone should not be a strict exclusion criterion. A pooled analysis of randomized clinical trials and observational studies showed that tolvaptan significantly slowed annual eGFR decline over 3 years of follow-up vs standard of care (-2.33 vs -3.99 mL/min/ 1.73 m²/year; p=0.009) in older individuals with ADPKD. [Kidney Int 2025;107:S1- S239; Kidney Med 2023;5:100639]
“For safe use in older patients, rigorous screening for contraindications should be performed before initiating treatment, with therapy started at a lower dose and gradually titrated up to a target of 120 mg daily in two divided doses [90/30 mg] as tolerated,” Kim advised.
