Efficacy Study of Water Drinking on PKD Progression. (ESWP)

• GFR estimated by plasma creatinine and cystatin C. [ Time Frame: One year (12 months) ] [ Designated as safety issue: No ]
  The relationship between urine volume (and urine osmolality) and change of GFR.
• Plasma AVP (Copeptine) level. [ Time Frame: 4-8-12 months ] [ Designated as safety issue: No ]
  The relationship between urine volume (osmolality) and plasma AVP.
• QOL questionnaire. [ Time Frame: 4-8-12 months ] [ Designated as safety issue: No ]
  The relationship between QOL and urine volume.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disease. Numerable cysts develop in renal tubule cells, which cause progressive renal enlargement and functional deterioration in ADPKD. Tubule cells proliferation is stimulated by 3'-5'-cyclic adenosine monophosphate (cAMP). Arginine vasopressin (AVP) operates through stimulation of cAMP, hence contributing renal enlargement in ADPKD patients. Studies in animal models of ADPKD provide convincing evidence that antagonizing AVP action results in inhibition of disease progression. It is postulated that large water intake in patients with ADPKD will decrease plasma AVP concentration and mitigate the action of cAMP on the renal tubule resulting in the amelioration of disease progression. However the effects of long-standing water intake on plasma AVP level and cyst development in ADPKD patients are not known. Therefore, long-term (12 months) efficacy study of water diuresis induced by oral water intake on kidney volume and renal function in ADPKD patients are designed.

Half of the consented patients (n=15) are encouraged to take large amount of water (2.5 ~ 3 L water intake daily for 12 months. 50ml/Kg BW/day). However when large amount water intake is not sustainable, patients can reduce the amount of water intake to the levels as much as large they can sustain.

Another half of the patients (n=15) are free to access water, according to their own habitual manner.

The urine volume and osmolality are expected to distribute relatively wide range. Analysis of the effects of water intake on TKV and GFR is expected to be possible.

The patients who visit Kyorin University Hospital.

• Autosomal Dominant Polycystic Kidney Disease.
• Disease Progression

• Water Load Group
  Water load group: 2.5 ~ 3 L water intake daily for 12 months (50ml/Kg BW/day). When large amount water intake is not sustainable, patients can reduce the amount of water intake to the levels as much as large he or she can sustain.
• Non-Water Loaded Group
  Non-water load group: The patients are free to access water intake, as they like.

Inclusion Criteria:

• The patients with ADPKD
• The patients who consent to the study protocol
• eGFR or Creatinine Clearance greater than 50ml/min/1.73m2

Exclusion Criteria:

• Patients who might be danger to drink large amount of water such as having heart failure or past history of cerebrovascular or cardiovascular disorders.
• The patients who take habitual medication which affects the AVP action such as SSRI (Selective serotonin reuptake inhibitors), tricyclic antidepressants or diuretics.
• The patients who is considered inappropriate by physicians.