Kidney Week

Abstract: PO2537

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease

Session Information

• Late-Breaking Clinical Trials Posters
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Rangan, Gopi, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Gopi Rangan,

• Wong, Annette, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Annette Wong,

• Munt, Alexandra, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Alexandra Munt,

• Zhang, Jennifer, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Jennifer Zhang,

• Saravanabavan, Sayanthooran, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Sayanthooran Saravanabavan,

• Allman-Farinelli, Margaret, The University of Sydney, Sydney, New South Wales, Australia

Margaret Allman-Farinelli,

• Badve, Sunil, Saint George Hospital, Kogarah, New South Wales, Australia

Sunil Badve,

• Boudville, Neil, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

Neil Boudville,

• Erickson, Bradley J., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Bradley J. Erickson,

• Fernando, Mangalee Renuka, Prince of Wales Hospital, Sydney, New South Wales, Australia

Mangalee Renuka Fernando,

• Foster, Sheryl L., Westmead Hospital, Westmead, New South Wales, Australia

Sheryl L. Foster,

• Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Adriana Gregory,

• Haloob, Imad A., Bathurst Hospital, Bathurst, New South Wales, Australia

Imad A. Haloob,

• Hawley, Carmel, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

Carmel Hawley,

• Johnson, David W., Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

David W. Johnson,

• Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Timothy L. Kline,

• Lee, Vincent W.S., Westmead Institute for Medical Research, Westmead, New South Wales, Australia

Vincent W.S. Lee,

• Lonergan, Maureen A., Wollongong Hospital, Wollongong, New South Wales, Australia

Maureen A. Lonergan,

• Pascoe, Elaine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

Elaine Pascoe,

• Rangan, Anna M., The University of Sydney, Sydney, New South Wales, Australia

Anna M. Rangan,

• Roger, Simon D., Gosford Hospital, Gosford, New South Wales, Australia

Simon D. Roger,

• Sud, Kamal, Nepean Hospital, Penrith, New South Wales, Australia

Kamal Sud,

• Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Vicente E. Torres,

• Adinarayanan, Sundareswari V., John Hunter Hospital, New Lambton Heights, New South Wales, Australia

Sundareswari V. Adinarayanan,

• Harris, David, Westmead Institute for Medical Research, Westmead, New South Wales, Australia

David Harris,

Group or Team Name

• On behalf of the PREVENT-ADPKD clinical trial investigators

Background

Arginine vasopressin (AVP) promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increasing water intake to reduce urine osmolality and AVP release is hypothesized to slow kidney cyst growth in ADPKD.

Methods

In this multi-center, open-label, parallel-arm randomized controlled 3-year trial adults with ADPKD and Mayo Subclass 1B to 1E and an estimated glomerular filtration rate (eGFR) of ≥30 mL per minute per 1.73m², were randomized to water intake prescribed to reduce 24-hour urine osmolality to ≤270 mOsm/kg or ad libitum water intake irrespective of urine osmolality. The primary endpoint was the annualized rate of change in the height-corrected total kidney volume (Ht-TKV).

Results

One hundred and eighty-four patients, with a mean 24-hour urine osmolality of 423±178mOsm/kg and median 24-hour urine volume of 2.3L/day (IQR:1.8-3.1L/day) at baseline, were randomized to either ad libitum water intake (92 patients) or prescribed water intake (92 patients). Over 3 years the mean treatment differences between the ad libitum water and prescribed water intake groups for 24-hour urine osmolality and 24-hour urine volume were -91 mOsm/kg (95% CI –127 to -54 mOsm/kg;P<0.01) and 0.6L/day (95% CI 0.4 to 0.9L/day;P<0.01) respectively. The proportion of patients with 24-hour urine osmolality <300 mOsm/kg for >50% of timepoints was 52%. There was no difference in the percentage annualized rate of change in Ht-TKV between the groups (ad libitum water intake: 7.8% per year, 95% CI, 6.6 to 9.0%; prescribed water intake: 6.8% per year, 95% CI 5.8 to 7.7%; P=0.18). The decline in eGFR from baseline to 3 years, changes in other secondary endpoints, discontinuation rates and adverse events were comparable between the two groups.

Conclusion

In ADPKD patients with a median baseline urine volume of 2.3L/day with Mayo subclass 1B to 1E, prescribed water intake was a safe intervention which achieved target urine osmolality in half of the patients but did not change the progression of total kidney volume over 3 years compared to ad libitum water intake.

Funding

• Commercial Support – Danone Research