Treating Metabolic Acidosis in Chronic Kidney Disease to Prevent Adverse Kidney and Cardiovascular Outcomes
NCT Number: NCT06545461
Status: COMPLETED
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Chronic Kidney Diseases|Cardiovascular Diseases|Hypertension
Interventions: OTHER: Fruits and Vegetables (F+V)|OTHER: Sodium Bicarbonate (NaHCO3)|OTHER: Usual Care
Sponsor: University of Texas at Austin
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 108
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 1998-06-22
Completion Date: 2016-10-30

Summary:
Upon completion, this project will determine if treatment of metabolic acidosis in non-diabetic study participants with reduced kidney function (chronic kidney disease \[CKD\] stage 3) associated with high blood pressure (hypertension) and macroalbuminuria, the latter indicating pronounced kidney injury, using either base-producing fruits and vegetables (F+V) or standard therapy for treatment of metabolic acidosis with the medication sodium bicarbonate (NaHCO3) 1) slows progression of CKD toward end-stage renal disease \[ESRD\]; 2) improves indices of cardiovascular disease (CVD) risk; and 3) better preserves plasma acid-base parameters. These studies are designed to compare the differential effects of treating the metabolic acidosis of CKD with F+Vs or NaHCO3 on kidney outcomes, including progression to ESRD, on indices of CVD risk and on plasma acid-base parameters.

Primary Outcome Measures: Difference in estimated glomerular filtration rate (eGFR) at follow up, eGFR (ml/min/1.73 m2) will be calculated using measured serum creatinine and cystatin-C concentrations, age, sex, and whether or not of African American ethnicity using a standard accepted formula.

eGFR will be compared among the three groups yearly up to 10 years follow up to assess chronic kidney disease (CKD) progression. Milestone assessments will be done at 3, 5, and 10 years. Higher eGFR indicates better-preserved kidney function. The investigators hypothesize that F+V or NaHCO3 will lead to better preserved (higher) eGFR., eGFR will be measured at baseline and yearly for 10 years|Difference in the rate of eGFR change during follow up, The rate of eGFR change (ml/min/1.73 m2/year) will assess CKD progression. It will be calculated by dividing the net change in eGFR between the milestone year of follow up and baseline divided by the years of follow up. The investigators hypothesize that F+V or NaHCO3 will lead to a slower rate of eGFR change, indicative of slower CKD progression., eGFR rate of change will be measured at 3, 5, and 10 years|Difference in the net eGFR change during follow up, The net eGFR change (ml/min/1.73 m2) will assess CKD progression and will be calculated by subtracting the milestone value from the baseline value. The investigators hypothesize that dietary acid reduction will lead to a smaller net eGFR change, indicative of less CKD progression., eGFR net change compared to baseline will be measured at 3, 5, and 10 years|Difference in the number of participants who reach need for kidney replacement therapy (KRT), Differences in the number of participants who reach the need for KRT will be determined by comparing the number of participants among arms who reach the need for dialysis or kidney transplant; this is a measure of how well the interventions protect kidney health. The investigators hypothesize that the F+V or NaHCO3 arms will have fewer participants reaching KRT., Number of participants reaching KRT will be determined at years 3, 5, and 10 from baseline|Difference in change in urine albumin excretion during follow up, CKD progression will be assessed by change in the urine albumin (mg)-to-creatinine (g) ratio (UACR) in a "spot" urine. An increased UACR is indicative of kidney injury and risk for subsequent decrease of kidney function with time. A decrease in UACR is indicative of reduced kidney injury and a lower risk for decreased kidney function with time. The investigators hypothesize that F+V or NaHCO3 will lead to a lower UACR.

• UACR will be compared among the three groups as follows: Value at 3,5, and 10 years Net change compared to baseline value at 3, 5, and 10 years, UACR will be measured at baseline and yearly for 10 years|Difference in change in urine N-acetyl-D -glucosaminidase (UNAG) excretion during follow up, CKD progression will be assessed by change in the UNAG (Units)-to-creatinine (g) ratio in a "spot" urine. An increased UNAG/creatinine ratio is indicative of increased kidney injury. The investigators hypothesize that F+V or NaHCO3 will lead to a lower UNAG/creatinine.

• UNAG/creatinine will be compared among the three groups as follows: Value at 3, 5, and 10 years Net change compared to baseline at 3, 5, and 10 years, UNAG will be measured at baseline and yearly for 10 years|Difference in change in urine angiotensinogen (UATG) excretion during follow up, CKD progression will be assessed by change in the UATG (ug)-to-creatinine (g) ratio in a "spot" urine. An increased UATG/creatinine ratio is an indirect measure of kidney levels of angiotensin II and is indicative of increased kidney injury. The investigators hypothesize that F+V or NaHCO3 will lead to a lower UATG/creatinine ratio.

• UATG/creatinine will be compared among the three groups as follows: Value at 3, 5, and 10 years Net change compared to baseline at 3, 5, and 10 years, UATG will be measured at baseline and yearly for 10 years
Secondary Outcome Measures: Difference in change in serum LDL cholesterol level during follow up, Higher serum LDL cholesterol levels (mg/dl) are an indicator of increased cardiovascular disease (CVD) risk. The investigators hypothesize that F+V leads to lower LDL cholesterol than that done with either NaHCO3 or Usual Care.

Comparisons among the three groups will be done as follows:

1. level at 3, 5, and 10 years
2. Net change compared to baseline at 3, 5, 10 years, Serum LDL cholesterol will be measured at baseline and yearly for 10 years|Difference in change in serum HDL cholesterol level during follow up, Higher serum HDL cholesterol levels (mg/dl) are an indicator of decreased CVD risk. The investigators hypothesize that F+V leads to higher HDL cholesterol than that done with either NaHCO3 or Usual Care.

Comparisons among the three groups will be done as follows:

1. level at 3, 5, and 10 years
2. Net change compared to baseline at 3, 5, and 10 years, Serum HDL cholesterol will be measured at baseline and yearly for 10 years|Difference in change in serum Lp(a) cholesterol level during follow up, Higher serum Lp(a) cholesterol levels (mg/dl) are an indicator of higher CVD risk. The investigators hypothesize that F+V leads to lower Lp(a) cholesterol than either NaHCO3 or Usual Care.

Comparisons among the three groups will be done as follows:

1. level at 3, 5, and 10 years
2. Net change compared to baseline at 3, 5, and 10 years, Serum Lp(a) cholesterol will be measured at baseline and yearly for 10 years|Difference in change in urine isoprostane 8-isoprostaglandin F2α excretion follow up, Higher urine excretion of isoprostane 8-isoprostaglandin F2α (U8-iso) is an indicator of increased oxidative stress which contributes to increased CVD risk. It will be measured as 8-iso (ug)-to-creatinine (g) ratio in a "spot" urine. The investigators hypothesize that F+V or NaHCO3 lead to a lower urine 8-iso/creatinine ratio.

Comparisons among the three groups will be done as follows:

1. level at 3, 5, and 10 years
2. Net change compared to baseline at 3, 5, and 10 years, Urine Isoprostane 8-isoprostaglandin F2α to creatinine ratio will be measured at baseline and yearly for 10 years.]|Difference in change in plasma pH during follow up, Plasma pH (pH is expressed numerically without units) will be measured with standard blood gas machine techniques. The investigators hypothesize that F+V or NaHCO3 will lead to higher values for plasma pH.

Comparisons among the three groups will be as follows:

* Levels at 3, 5, and 10 years
* Net change compared to baseline at 3, 5, and 10 years, Plasma pH will be measured at baseline and yearly for 10 years|Difference in change in plasma partial pressure of carbon dioxide gas (PCO2) during follow up, Plasma PCO2 \[millimeter (mm) mercury (Hg)\], will be measured with standard blood gas machine techniques. The investigators hypothesize that F+V or NaHCO3 will lead to higher values for plasma PCO2.

Comparisons among the three groups will be as follows:

* Levels at 3, 5, and 10 years
* Net change compared to baseline at 3, 5, and 10 years, Plasma PCO2 will be measured at baseline and yearly for 10 years|Difference in change in plasma bicarbonate concentration (HCO3-]) during follow up, Plasma \[HCO3-\] (mEq/l) will be calculated from measured values of plasma pH and plasma partial pressure of carbon dioxide gas (PCO2) with a conventional formula commonly used by clinical laboratories. The investigators hypothesize that F+V or NaHCO3 will lead to higher values for plasma \[HCO3-\].

Comparisons among the three groups will be as follows:

* Levels at 3, 5, and 10 years
* Net change compared to baseline at 3, 5, and 10 years, Serum [HCO3-] will be measured at baseline and yearly for 10 years|Difference in change in plasma total CO2 (TCO2) during follow up, Plasma TCO2 \[millimolar (mM)\] will be measured by the PI as in previous studies using fluorimetry. This technique uses an enzymatic assay in which TCO2 reacts with phosphoenolpyruvate to form oxaloacetate, which is reduced to malate coupled with oxidation of nicotinamide adenine dinucleotide bound to hydrogen ion (NADH) to nicotinamide adenine dinucleotide without hydrogen ion (NAD+). NADH fluoresces but NAD+ does not, allowing for quantitation of TCO2 as reduced fluorescence. This technique is more reproducible than the conventional one of measuring CO2 gas released upon addition of a strong acid.

Measuring changes in plasma TCO2 will help assess the effect(s) of dietary acid reduction among the three groups. The investigators hypothesize that F+V or NaHCO3 will lead to higher values for plasma TCO2.

Comparisons among the three groups will be as follows:

* Levels at 3, 5, and 10 years
* Net change compared to baseline at 3, 5, and 10 years, Plasma TCO2 will be measured at baseline and yearly for 10 years