Haemodialysis Salt Reduction Study
Condition: Kidney Failure, Chronic; Hypertension
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Study type: Interventional

Summary: 
      High blood pressure (hypertension) affects up to 80% of all patients receiving haemodialysis
      for chronic kidney disease (CKD). High blood pressure is a major cause cardiovascular disease
      (i.e. strokes, heart attacks and heart failure) and, thereby, cardiovascular deaths in these
      patients.

      A significant cause of raised blood pressure in haemodialysis patients is thought to be due
      to retention of salt in the body. In healthy people the kidneys excrete salt but the kidneys
      of patients with CKD cannot do this, so salt has to be removed by dialysis. However dialysis
      cannot remove as much salt as is necessary, and so it accumulates. This fact has been
      recognized for many years, and health professionals caring for haemodialysis patients often
      stress the importance of restriction of dietary salt intake.

      However no research has looked in detail at the mechanisms by which salt raises blood
      pressure in haemodialysis patients. It is likely that salt directly affects thirst, causing
      patients to drink more and become overloaded with fluid. In addition, salt may have direct
      effects on the blood vessel wall, causing failure of adequate blood vessel relaxation. Both
      of these factors may raise blood pressure.

      We will conduct a carefully controlled crossover study looking at the effects of a modest
      reduction in salt intake on BP. During the course of the study, which will last eight weeks,
      patients will receive both a 5 gram per day and a 10 gram per day salt intake. We will look
      at how thirst, fluid intake, a number of markers of blood vessel function and blood pressure
      differ on these two salt intakes.
    

Detailed description: 
      High blood pressure (BP) is a major independent risk factor for cardiovascular mortality in
      individuals on haemodialysis, and yet BP is extremely poorly controlled in this population.

      Excessive dietary salt intake is likely to be a major cause of hypertension in these
      patients. Firstly, excessive salt intake will result in thirst, excessive fluid intake and
      weight gains between dialysis, and thereby chronic over-expansion of extracellular fluid
      volumes resulting in high blood pressure. Secondly, salt may have direct effects on the
      arterial tree contributing to endothelial dysfunction that has clearly been demonstrated in
      uraemic individuals, including haemodialysis patients. Abnormalities in endothelial nitric
      oxide (NO) production may play an important role in salt-sensitive hypertension, mediated by
      the potent inhibitor of NO synthase, asymmetrical dimethylarginine (ADMA). Plasma ADMA
      concentrations are several-fold higher in individuals on dialysis than in normal controls,
      and it would be of interest to see whether ADMA concentrations decrease with a reduction
      dietary salt intake.

      In spite of the importance of dietary salt intake in haemodialysis patients, there are no
      controlled studies which delineate the mechanisms by which salt intake affects BP. We propose
      to conduct a prospective double-blind placebo controlled cross-over study of normal (10 to 12
      grams salt per day) versus modestly reduced (6 grams per day) salt intake over an eight week
      period in haemodialysis patients. The primary outcome measure is the change in pre-dialysis
      systolic BP. Other outcome measures include mean systolic and diastolic BP as measured by
      ABPM, thirst scores, daily weight gains and thoracic fluid content, as measured by thoracic
      bioimpedance. Furthermore, in a sub-group of subjects will we study the changes in plasma
      ADMA concentrations with reductions in salt intake, and examine correlations with changes in
      BP and systemic vascular resistance.
    

Intervention name(s): Slow Sodium
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: End-stage renal failure; Haemodialysis; Sodium; Blood Pressure