Effects of Low Sodium Intake on the Anti-proteinuric Efficacy in Hypertensive Patient With Olmesartan
Condition: Hypertension; Chronic Kidney Disease; Microalbuminuria
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      Purpose of this study

        1. Intensive education for low salt diet will be enhance the anti-proteinuric effect of
           Olmesartan, a popular anti-hypertensive drug of angiotensin II receptor blocker, in
           Koreans compared to conventional prescription of medication.

        2. Intensive education for low salt diet will decrease the amount of 24 hour-urine sodium
           excretion compared to control group, effectively.
    

Detailed description: 
      1. Background

           A. The chronic kidney disease (CKD) is the one of the main burden of chronic diseases
           and the prevalence of CKD is increasing in worldwide. In Korea, the prevalence of CKD
           was reported as 13.7% among urban Korean adults in 2008 by our study group.

           B. It is well known the CKD is the most important risk factor to cardiovascular events,
           cardiovascular mortality, all cause-mortality, and hospitalization. The cost of the
           management for the CKD was high and it took 3.25% of all budgets for medical
           reimbursement in 2004 for all Koreans, which was ranked on the top of expenditure for
           single disease category.

           C. The most popular risk factors to CKD progression are aging, obesity, hyperlipidemia,
           diabetes mellitus, hypertension, and proteinuria. The hypertension and proteinuria also
           cause the cardiovascular events and increase the mortality rate.

           D. The inhibitors for renin-angiotensin aldosterone system, angiotensin II type I
           receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI), are well
           known medications to prevent cardiovascular events and renal functional deterioration to
           end stage renal disease(ESRD) in patients with hypertension, non-diabetic CKD, or
           diabetic nephropathy. One of the adverse events of ARB is the decrease of hemoglobin.
           Inoue et al reported the level of hemoglobin was decreased in amount of 0.45 ±0.89 g/dL
           after prescription of ARB and valsartan decreased the erythropoietin in 6 days after
           medication. The exact mechanism of decrease of hemoglobin by ARB was not fully verified
           but it is related to decrease effects of angiotensin II on aggravating hypoxia in the
           kidney and on the activation of hypoxia-inducible factor 1α (HIF1a) and then decrease
           the production of erythropoietin as in the report of Durmus et al. Considering that the
           relationships between ARB usage and decrease of proteinuria in transplanted kidney,
           between aggravation of hypoxia or HIF1a and CKD, and between ARB and the decrease of
           HIF1a or erythropoietin(EPO), we could postulate that the decrease of hemoglobin would
           not be a adverse effect of ARB to deteriorate patients' condition but a co-phenomenon of
           ARB's anti-RAS effect and a marker of ARB's effectiveness.

           E. The anti-proteinuric effect of ARB is decreased by high salt intake. For example, ARB
           treatment without low salt intake decreased proteinuria by 30% in patients with
           proteinuria 2-10g/day compared to baseline value and addition of low salt diet to ARB
           treatment further decreased proteinuria up to 25%. But, using slow salt tablets,
           increase of daily intake of sodium diminished the anti-proteinuric effect of ARB in
           diabetic nephropathy.

           F. The previous studies for the effect of ARB on proteinuria affected by sodium intake
           took the methods of controlled diet by researcher or using slow salt tablet but these
           method are not practical to adopt in real clinical practice.

           G. The moderate and mild decrease of daily sodium intake which lower the daily excretion
           of sodium by 55 mEq/day had an effect of decrease of proteinuria by 11% in hypertensive
           patients.

           H. The mean amount of sodium of Korean diets was reported as high as 208 mmol/day in
           Intersalt study, which is more than 11 g of salt. The recent reports also showed the
           trend of high salt-intake by Koreans.

        2. Rationale So, It is worth to do this study because

             -  high salt intake is prevalent in Koreans,

             -  high salt diet diminishes the effect of ARB on proteinuria

             -  the methods used in previous studies were not suitable to apply to clinical
                practice,

             -  and there were no study to reveal the decrease of hemoglobin would the marker for
                the effect of ARB and not be a adverse event of ARB.

        3. Objectives

             1. Primary objective: The difference between amount of albuminuria after usage of
                Olmesartan and amount of albuminuria after prescription of Olmesartan with
                intensive diet education in intervention group is higher than the difference of
                albuminuria in control group.

             2. Secondary objective:

           Item 1: In all patients, Olmesartan decreases the albuminuria. Item 2: In all patients,
           the change of hemoglobin after prescription of Olmesartan is proportional to the change
           of albuminuria and serum erythropoietin.

           Item 3: Intensive education for low salt diet induces the significant decrease of daily
           sodium excretion in Intervention group compared to control group.

           Item 4: Intensive education for low salt diet induces the significant decrease of blood
           pressure in Intervention group compared to control group.

        4. Study Flow

             -  Period

                  1. Washout period (-8 weeks;Point 0 to 0 weeks; Point 1)

                  2. Olmesartan Period ( 0 week; point 1 to 8 weeks; point 2)

                  3. Intervention period (8 week ; point 2 to 16 weeks; point 3)

             -  For patients with taking ACEI, other ARB, diuretics, or renin inhibitor, already;
                Initial wash-out period for 8 weeks, and then (point 1) prescription of Olmesartan
                40 mg qd for 8 weeks, and then (point 2) allocation to Intensive group or control
                group for 8 weeks, and then the study will be over (point 3).

             -  For patients without taking ACEI, other ARB, diuretics, or renin inhibitor; For
                initial 8 weeks, adjust the blood pressures around 140/90 mmHg, and then (point 1)
                prescription of Olmesartan 40 mg qd for 8 weeks, and then (point 2) allocation to
                Intensive group or control group for 8 weeks, and then the study will be over
                (point 3).

             -  Blood pressure control Adjust the blood pressures around 140/90 mmHg with other
                hypertensive drugs except ACEI, other ARB, diuretics, or renin inhibitor during
                whole period.

             -  Intensive diet education:

      For 8 weeks, dietitian will call patients to take the information according to pre-defined
      questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen
      sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.
    

Intervention name(s): Intensive education of low salt diet
Intervention type(s): Behavioral
Intervention description(s): For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.
Other intervention name(s): low salt diet; Angiotensin II converting enzyme; albuminuria; chronic kidney disease
Intervention MeSH terms: Angiotensin II
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hypertension; Chronic kidney disease; albuminuria; low salt diet; Angiotensin II receptor blocker