The Effect of High and Low Sodium Intake on Urinary Aquaporin-2 in Autosomal Dominant Polycystic Kidney Disease
Condition: Polycystic Kidney, Autosomal Dominant
MeSH terms: Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional

Summary: 
      The aim of the study is to test the following hypotheses:

        1. that the function and/or regulation of AQP2 and /or ENaC in the principal cells is
           abnormal in autosomal dominant polycystic kidney disease.

        2. if an abnormal function of the principal cells is present in autosomal dominant
           polycystic kidney disease, this will become more pronounced at high and low sodium
           intake.
    

Detailed description: 
      Recruitment:

      The patients with ADPKD are recruited from the Outpatient Nephrology Clinic of the Department
      of Medicine, Holstebro Hospital (Holstebro, Denmark). The control subjects are recruited by
      advertising in public institutions and private companies.

      Number of Subjects:

      A difference in u-AQP2CR of 40 ng/mmol is considered the minimal relevant difference. A
      sample size of 10 subjects, who can be evaluated, has 80% power to detect this difference
      assuming a level of signiﬁcance of 5% and an SD of 30 ng/mmol. Because a few subjects are
      expected to drop out, 14-15 subjects will be included in each group.

      Experimental Procedure Before the Study Day:

      Five days before the study day, the subjects collect a standardized, HS (300 mmol
      sodium/day/17.5 g salt/day) or LS (30 mmol sodium/day/1.8 g salt/day), 4-day diet from the
      hospital kitchen. Depending on the individually estimated energy requirement, the
      participants are given either a diet of 8,000 or 11,000 kJ/day. The energy distribution is
      55% carbohydrates, 15% proteins, and 30% lipids. The 4-day diet is started the following
      morning. The ﬂuid intake is also standardized during the 4 days. The subjects are asked to
      drink exactly 250 ml/1,000 kJ/day and to abstain from coffee, tea, and alcoholic beverages.
      The subjects are instructed to keep their physical activity unchanged during the two
      experiments and to abstain from hard training. The subjects have to collect their urine for
      24 h the day before the study day.

      Experimental Procedure on the Study Day:

      On the study day, the subjects are asked to drink 175 ml of water every 30 min from 7:00 AM.
      The subjects arrive at the department at 8:00 AM. Peripheral iv lines are inserted into the
      antecubital veins of both forearms, one for infusion of 51Cr-EDTA and hypertonic saline, and
      one for withdrawal of blood samples. The subjects will be kept in the supine position from
      8:00 AM to 1:30 PM except during voiding, which will take place in the sitting or standing
      position. At 8:30 AM, a priming dose of 51Cr-EDTA is administered, followed by sustained
      infusion. After 60 min of equilibration, the study will continue with ﬁve clearance periods,
      the ﬁrst two of 30-min duration (P1-P2), the last three of 60-min duration (P3-P5). The ﬁrst
      two clearance periods are baseline periods. At 10:30 AM, 7 ml/kg of 3% saline is given over
      30 min. Blood pressure and heart rate are measured every 30 min from 9:30 AM to 1:30 PM.
      Urine is collected in each clearance period and analyzed for sodium, osmolality, u-AQP2,
      u-ENaC-betaCR, u-cAMP, u-PGE2, and 51CrEDTA. Blood samples will be drawn every 30 min from
      9:30 AM to 10:30 AM and every hour from 11:30 AM to 1:30 PM, and will be analyzed for sodium,
      osmolality, and 51Cr-EDTA. In addition, analysis of p-AVP, p-Renin, p-ANG II, p-Aldo, p-ANP,
      and p-BNP will be performed from blood samples drawn at 10:30 AM, 11:30 AM, 12:30 PM, and
      1:30 PM.

      Statistics:

      Statistical analyses will be performed using SPSS version 15 (SPSS, Chicago, IL). Single
      baseline values are obtained by taking the weighted average of the measurements from the two
      baseline periods. The baseline values of the two groups will be compared by Student's t-test.
      The baseline values during HS and LS intake will be compared by paired samples t-tests. The
      investigators will use the "General Linear Model Repeated Measures" procedure in SPSS with
      time as the within-subject factor and group as the between-subject factor to compare the
      effect variables in patients and controls. The changes in response to the hypertonic saline
      infusion in each group will be analyzed with the General Linear Model Repeated Measures
      procedure with time as the within-subject factor and paired samples t-tests with Bonferroni
      correction as post hoc tests. P values Recruitment The patients with ADPKD will be recruited
      from the Outpatient Nephrology Clinic of the Department of Medicine, Holstebro Hospital
      (Holstebro, Denmark). The control subjects will be recruited by advertising in public
      institutions and private companies.

      Number of Subjects A difference in u-AQP2CR of 40 ng/mmol is considered the minimal relevant
      difference. A sample size of 10 subjects, who could be evaluated, has 80% power to detect
      this difference assuming a level of signiﬁcance of 5% and an SD of 30 ng/mmol. Because a few
      subjects are expected to drop out, 14-15 subjects will be included in each group.

      Experimental Procedure Before the Study Day Five days before the study day, the subjects will
      collect a standardized, HS (300 mmol sodium/day/17.5 g salt/day) or LS (30 mmol
      sodium/day/1.8 g salt/day), 4-day diet from the hospital kitchen. Depending on the
      individually estimated energy requirement, the participants will be given either a diet of
      8,000 or 11,000 kJ/day. The energy distribution will be 55% carbohydrates, 15% proteins, and
      30% lipids. The 4-day diet will start the following morning. The ﬂuid intake is also
      standardized during the 4 days. The subjects are asked to drink exactly 250 ml/1,000 kJ/day
      and to abstain from coffee, tea, and alcoholic beverages. The subjects will be instructed to
      keep their physical activity unchanged during the two experiments and to abstain from hard
      training. The subjects have to collect their urine for 24 h the day before the study day.

      Experimental Procedure on the Study Day On the study day, the subjects are asked to drink 175
      ml of water every 30 min from 7:00 AM. The subjects arrive at the department at 8:00 AM.
      Peripheral iv lines will be inserted into the antecubital veins of both forearms, one for
      infusion of 51Cr-EDTA and hypertonic saline, and one for withdrawal of blood samples. The
      subjects will be kept in the supine position from 8:00 AM to 1:30 PM except during voiding,
      which will take place in the sitting or standing position. At 8:30 AM, a priming dose of
      51Cr-EDTA is administered, followed by sustained infusion. After 60 min of equilibration, the
      study will continue with ﬁve clearance periods, the ﬁrst two of 30-min duration (P1-P2), the
      last three of 60-min duration (P3-P5). The ﬁrst two clearance periods are baseline periods.
      At 10:30 AM, 7 ml/kg of 3% saline is given over 30 min. Blood pressure and heart rate will be
      measured every 30 min from 9:30 AM to 1:30 PM. Urine is collected in each clearance period
      and analyzed for sodium, osmolality, u-AQP2, u-ENaC-betaCR, u-cAMP, u-PGE2, and 51CrEDTA.
      Blood samples will be drawn every 30 min from 9:30 AM to 10:30 AM and every hour from 11:30
      AM to 1:30 PM, and will be analyzed for sodium, osmolality, and 51Cr-EDTA. In addition,
      analysis of p-AVP, p-Renin, p-ANG II, p-Aldo, p-ANP, and p-BNP will be performed from blood
      samples drawn at 10:30 AM, 11:30 AM, 12:30 PM, and 1:30 PM.

      Statistics Statistical analyses will be performed using SPSS version 15 (SPSS, Chicago, IL).
      Single baseline values are obtained by taking the weighted average of the measurements from
      the two baseline periods. The baseline values of the two groups will be compared by Student's
      t-test. The baseline values during HS and LS intake will be compared by paired samples
      t-tests. The investigators will use the "General Linear Model Repeated Measures" procedure in
      SPSS with time as the within-subject factor and group as the between-subject factor to
      compare the effect variables in patients and controls. The changes in response to the
      hypertonic saline infusion in each group will be analyzed with the General Linear Model
      Repeated Measures procedure with time as the within-subject factor and paired samples t-tests
      with Bonferroni correction as post hoc tests. P values ≤0.05 will be considered signiﬁcant.
    

Intervention name(s): High Sodium Diet; Low Sodium Diet; Hypertonic saline infusion
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): 250-350 mmol; 25-35 mmol; 7 ml/ kg of 3% saline were given over 30 minutes.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: ADPKD; Urinary Aquaporin-2; ENaC; Fractional sodium excretion; High/low sodium diet