Why is high water intake recommended in autosomal dominant polycystic kidney disease?

Why High Water Intake is Recommended in ADPKD

The theoretical rationale for high water intake in ADPKD is to suppress vasopressin (which drives cyst growth), but current evidence does NOT support this intervention as beneficial for slowing disease progression, and patients should simply drink to satisfy thirst while avoiding dehydration. 1

The Theoretical Mechanism

The recommendation for high water intake stems from the biological understanding that:

• Vasopressin promotes cyst growth in ADPKD through cAMP-mediated pathways, making it a key therapeutic target 2, 3, 4
• High water intake theoretically suppresses endogenous vasopressin production, which could potentially slow cyst progression 1
• Patients with ADPKD are more sensitive to water deprivation than those with other kidney diseases, producing higher vasopressin levels to achieve similar urine osmolality compared to healthy individuals 1

The Evidence Does NOT Support High Water Intake

Despite the appealing biological rationale, interventional and observational studies have failed to confirm any benefit of prescribed high water intake:

• The largest randomized controlled trial (184 patients over 3 years) found NO difference in kidney volume growth between prescribed high water intake (targeting urine osmolality ≤270 mOsm/kg) versus ad libitum intake (7.8% vs 6.8% annual growth, P=0.18) 4
• Even when patients achieved the target urine osmolality, there was no reduction in serum copeptin (a vasopressin surrogate marker) over 3 years 4
• A randomized trial is still ongoing, indicating the question remains unresolved 1

Current Guideline Recommendations

The 2019 international consensus statement (Nature Reviews Nephrology) provides only a weak recommendation (evidence level D) that high water intake "may be beneficial" in slowing progression 1

The practical guidance is:

• Dehydration should be avoided 1
• Patients should be encouraged to drink to satisfy thirst rather than forcing excessive fluid intake 1
• A low-osmolar diet approach (combining low sodium <1,500 mg/day, low protein 0.8 g/kg, and adjusted water intake to achieve urine osmolality <280 mOsm/kg) can reduce copeptin levels in short-term studies, but long-term benefit on cyst growth remains speculative 1, 3

Practical Considerations and Caveats

If high water intake is attempted, be aware of:

• Hyponatremia risk: Two cases occurred in the high water group of one feasibility trial 2
• Quality of life impact: Substantial polyuria affects sleep and daily activities, similar to vasopressin antagonist therapy 1
• Adherence challenges: Only 52.3% of patients achieved target urine osmolality in the definitive trial despite intensive monitoring 4
• Adequate hydration (>2.5 L/day) is recommended as part of general lifestyle modifications, but this differs from aggressive water loading 5

Bottom Line

The widespread recommendation for high water intake in ADPKD is based on biological plausibility rather than proven clinical benefit. The most recent and highest quality evidence shows no impact on disease progression. Patients should maintain adequate hydration, avoid dehydration, and drink to thirst rather than forcing excessive water intake that may compromise quality of life without proven benefit. 1, 4