Dietary Acid Reduction and Progression of Chronic Kidney Disease
Condition: Chronic Kidney Diseases; Cardiovascular Diseases; Hypertension
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Cardiovascular Diseases
Study type: Interventional

Summary: 
      Upon completion, this project will determine if dietary acid reduction done with either
      fruits and vegetables (F+V) or the medication sodium bicarbonate (NaHCO3) in study
      participants with high blood pressure (hypertension) and initially normal kidney function but
      with signs of kidney injury 1) slows progression of chronic kidney disease (CKD); 2) improves
      indices of cardiovascular risk; and 3) better preserves acid-base status. These studies are
      designed to determine if the simple and comparatively inexpensive intervention of dietary
      acid reduction can prevent or reduce adverse outcomes in individuals with early-stage CKD.
    

Detailed description: 
      The long-term objective of this study is to determine if the simple and comparatively
      inexpensive intervention of dietary acid reduction can prevent or reduce adverse outcomes in
      individuals with hypertension and early-stage chronic kidney disease (CKD). The specific aims
      of this study are to determine if dietary acid reduction done with either base-producing
      fruits and vegetables (F+V) in amounts calculated to reduce participant dietary acid content
      by half or with sodium bicarbonate (NaHCO3, 0.4 milliequivalents (mEq)/kg body weight (bw),
      an amount designed to match the alkali content of the prescribed F+V) in participants with
      initially normal kidney function but with signs of kidney injury 1) slows progression of CKD;
      2) improves indices of cardiovascular risk; and 3) better preserves acid-base status. The
      incidence and prevalence of CKD is increasing along with increased incidence and prevalence
      of its adverse outcomes, including heart attack and stroke, the latter for which patients
      with CKD are at increased risk. Most modern diets produce acid when metabolized in the body
      and some studies suggest that the small amount of acid produced causes progressive and
      long-term injury to blood vessels in kidneys, heart, and brain, thereby increasing risk for
      kidney disease and its progression, heart attack and stroke. This study will recruit
      participants with hypertension and macroalbuminuria (urine albumin [mg]-to-creatinine [g]
      ratio > 200 mg/g) but with normal estimated glomerular filtration rate (eGFR) greater than or
      equal to 90 ml/min/1.73 m2) to be randomized to receive dietary acid reduction done with F+V
      or oral NaHCO3 or to no dietary acid reduction (Usual Care). At study entry and yearly for 5
      years, all participants will have 10 milliliters (ml) of blood drawn from an antecubital vein
      for measurement of pH, partial pressure of carbon dioxide (PCO2), total CO2 (TCO2),
      creatinine, cystatin-C, low-density lipoprotein (LDL) cholesterol, high density lipoprotein
      (HDL) cholesterol, Lp(a) cholesterol, sodium, potassium, chloride, and citrate. They will
      also have 20 ml of urine collected for measurement of creatinine, pH, TCO2, ammonium,
      titratable acidity, albumin, N-acetyl-D-glucosaminidase, angiotensinogen, isoprostane
      8-isoprostaglandin F2 alpha (8-iso), and citrate. Body acid will be measured in participants
      at baseline and at 5 years during an 8-hour protocol conducted in a Texas Tech University
      Health Sciences Center (TTUHSC) clinic. They will be told to fast after midnight and report
      to the TTUHSC clinic the following morning at which time they will be given a single oral
      dose of sodium bicarbonate (NaHCO3, 0.5 mEq/kg) and have 1 ml of blood drawn from a needle
      maintained in an arm vein for protocol duration for TCO2 before and at 2, 4, and 6 hours
      after the dose of NaHCO3 was given and urine collected over 8 hours for TCO2, pH, ammonium,
      and titratable acidity. The change in blood TCO2 in response to the amount of bicarbonate
      retained the body (dose minus urine bicarbonate excretion) will be used to calculate
      participant body acid. The course of serum and urine parameters over the 5 years of follow up
      in those randomized to F+V or NaHCO3 compared to Usual Care will help determine the effect of
      dietary acid reduction on CKD progression (change in eGFR and in urine indices of kidney
      injury), indices of cardiovascular disease risk (change in LDL, HDL, and Lp(a) cholesterol,
      and change in 8-iso), and on participant acid-base status (serum acid-base parameters (pH,
      PCO2, bicarbonate concentration [HCO3], TCO2, urine citrate excretion, and body acid
      measurement). These studies will also determine differences in these outcomes with dietary
      acid reduction done with F+V or NaHCO3.

      The investigators hypothesize that dietary acid reduction will 1) reduce kidney injury
      indicated by lower urine indices of kidney injury and slow kidney function decline indicated
      by slower eGFR decline rate; 2) improve indices of cardiovascular risk indicated by lower
      LDL, higher HDL, lower Lp(a) cholesterol, and lower 8-iso; and 3) improve acid-base status
      indicated by higher serum TCO2, higher urine citrate excretion, and lower body acid. The
      investigators additionally hypothesize that F+V will have greater benefits on indicators of
      parameters of cardiovascular risk than NaHCO3. Excretion of urine acid-base parameters will
      help determine effects of dietary acid reduction on urine acid excretion. Blood pH and PCO2
      will be measured using a blood gas analysis system and blood and urine concentrations of
      albumin and creatinine will be measured with standard techniques. Blood and urine TCO2 will
      be measured as done previously using fluorimetry techniques in the PI's laboratory. Urine
      ammonium, titratable acidity, N-Acetyl-beta-D-glucosaminidase, angiotensinogen, isoprostane
      8-isoprostaglandin F2 alpha and citrate will be measured as done previously in the laboratory
      of the Co-PI.
    

Intervention name(s): Fruits and vegetables (F+V); NaHCO3 Tablets; Usual Care
Intervention type(s): Other; Drug; Other
Intervention description(s): Participants will receive a prescribed amount of F+V designed to reduce their dietary acid intake by half. This typically amounts to 2-4 cups/day for each participant randomized to this group, depending on the type of F+Vs used, provided in weekly allotments. Participants will receive standard care for their medical concerns.; Participants will receive 0.4 mEq/kg bw NaHCO3 /day, an amount designed to match the alkali provided by the added F+V. This will be provided as 650 mg NaHCO3 tablets for an average of 4-5 tablets/day in 2 divided doses for each participant randomized to this group. Participants will receive standard care for their medical concerns.; Participants will receive standard care for their medical concerns and no additional alkali (F+V or NaHCO3).
Other intervention name(s): Baking soda
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: albuminuria