Dietary Acid Reduction and Progression of Chronic Kidney Disease

NCT06046924 | Completed

• 1 other identifier: L-INTMED-95987
• Study Type: interventional
• Target: 153
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Chronic Kidney Diseases; Cardiovascular Diseases; Hypertension

Keywords

albuminuria

Outcome Measures

Primary Outcomes (6)

• Difference in estimated glomerular filtration rate (eGFR) at 5 years 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 at 5 years follow up to assess chronic kidney disease (CKD) progression. Higher eGFR is indicative of better-preserved kidney function. The investigators hypothesize that dietary acid reduction will lead to better preserved (higher) eGFR at 5 years.

  eGFR will be measured at baseline and yearly for 5 years.

• Difference in the rate of eGFR change during 5 years follow up

  The rate of eGFR change (ml/min/1.73 m2/year) will assess CKD progression and will be calculated by dividing the net change in eGFR over 5 years (5-year value minus baseline value) and dividing by 5 years. The investigators hypothesize that dietary acid reduction will lead to a slower rate of eGFR change, indicative of less CKD progression.

  eGFR will be measured at baseline and yearly for 5 years.

• Difference in the net eGFR change during 5 years follow up

  The net eGFR change (ml/min/1.73 m2) will assess CKD progression and will be calculated by subtracting the 5-year 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 will be measured at baseline and yearly for 5 years.

• Difference in change in urine albumin excretion during 5 years follow up

  CKD progression will be assessed by change in the albumin (mg)-to-creatinine (g) ratio (ACR) in a "spot" urine. An increased ACR is indicative of kidney injury and risk for subsequent decrease of kidney function with time. A decrease in ACR is indicative of reduced kidney injury and a lower risk for decreased kidney function with time. The investigators hypothesize that dietary acid reduction will lead to a lower ACR. • ACR will be compared among the three groups as follows: * 5 year value * Net change (5 year value minus baseline value) at five years

  ACR will be measured at baseline and yearly for 5 years.

• Difference in change in urine N-acetyl-D -glucosaminidase (NAG) excretion during 5 years follow up

  CKD progression will be assessed by change in the NAG (Units)-to-creatinine (g) ratio in a "spot" urine. An increased NAG/creatinine ratio is indicative of increased kidney injury. The investigators hypothesize that dietary acid reduction will lead to a lower NAG/creatinine. • NAG/creatinine will be compared among the three groups as follows: * 5 year value * Net change (5 year value minus baseline value) at five years

  NAG/creatinine will be measured at baseline and yearly for 5 years.

• Difference in change in urine angiotensinogen (ATG) excretion during 5 years follow up

  CKD progression will be assessed by change in the ATG (ug)-to-creatinine (g) ratio in a "spot" urine. An increased ATG/creatinine ratio is an indirect measure of kidney levels of angiotensin II and is indicative of increased kidney injury. The investigators hypothesize that dietary acid reduction will lead to a lower ATG/creatinine ratio. • ATG/creatinine will be compared among the three groups as follows: * 5 year value * Net change (5 year value minus baseline value) at five years

  ATG/creatinine will be measured at baseline and yearly for 5 years.

Secondary Outcomes (11)

• Difference in change in serum LDL cholesterol level during 5 years follow up

  Serum LDL cholesterol will be measured at baseline and yearly for 5 years.

• Difference in change in serum HDL cholesterol level during 5 years follow up

  Serum HDL cholesterol will be measured at baseline and yearly for 5 years.

• Difference in change in serum Lp(a) cholesterol level during 5 years follow up

  Serum Lp(a) cholesterol will be measured at baseline and yearly for 5 years.

• Difference in change in urine Isoprostane 8-isoprostaglandin F2α excretion during 5 years follow up

  Urine Isoprostane 8-isoprostaglandin F2α to creatinine ratio will be measured at baseline and yearly for 5 years.

• Difference in change in serum pH during 5 years follow up

  Serum pH will be measured at baseline and yearly for 5 years.

Study Arms (3)

Fruits and vegetables (F+V)

EXPERIMENTAL

51 participants with hypertension, normal estimated glomerular filtration rate (eGFR) (\>90 ml/min/m2) and macroalbuminuria (albumin \[mg\] to creatinine \[g\] ratio \> 200 mg/g) will receive a prescribed amount of base-producing fruits and vegetables (F+V) designed to reduce their dietary acid intake by half. Depending on the particular foods used, this amounts to 2-4 cups daily of fruits and vegetables given in weekly allotments. They will otherwise receive standard care for their medical concerns including angiotensin converting enzyme inhibitor therapy for albuminuria and followed annually for 5 years.

Other: Fruits and vegetables (F+V)

NaHCO3 (HCO3)

EXPERIMENTAL

51 participants with hypertension, normal estimated glomerular filtration rate (eGFR) (\>90 ml/min/m2) and macroalbuminuria (albumin \[mg\] to creatinine \[g\] ratio \> 200 mg/g) will receive 0.4 mEq/kg/bw oral tablet dose of sodium bicarbonate (NaHCO3) designed to match the alkali intake of F+V. They will otherwise receive standard care for their medical concerns including angiotensin converting enzyme inhibitor therapy for albuminuria and followed annually for 5 years.

Drug: NaHCO3 Tablets

Usual Care (UC)

ACTIVE COMPARATOR

51 participants with hypertension, normal estimated glomerular filtration rate (eGFR) (\>90 ml/min/m2) and macroalbuminuria (albumin \[mg\] to creatinine \[g\] ratio \> 200 mg/g) will receive no additional alkali (neither F+V or NaHCO3) and will receive standard care for their medical concerns, including angiotensin converting enzyme inhibitor therapy for albuminuria and followed annually for 5 years.

Other: Usual Care

Interventions

Fruits and vegetables (F+V) OTHER

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.

Fruits and vegetables (F+V)

NaHCO3 Tablets DRUG

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.

Also known as: Baking soda

NaHCO3 (HCO3)

Usual Care OTHER

Participants will receive standard care for their medical concerns and no additional alkali (F+V or NaHCO3).

Usual Care (UC)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-malignant high blood pressure or hypertension
• years old
• Urine albumin-to-creatine ratio \> 200 mg/g creatinine
• Estimated glomerular filtration rate (eGFR) greater than or equal to 90 ml/min/1.73 m2
• Serum total CO2 (TCO2) \> 22 mmol/l
• Greater than or equal to 2 primary care visits in the preceding year
• Able to provide informed consent

You may not qualify if:

• Malignant hypertension or history thereof
• Primary kidney disease or findings consistent thereof such as \> 3 red blood cells per high powered field of urine or urine cellular casts
• History of diabetes or fasting glucose greater than or equal to 110 mg/dl
• History of hematologic disorders, malignancies, chronic infections, current pregnancy, history or clinical evidence of cardiovascular disease
• Peripheral edema or diagnosis associated with edema such as heart/liver failure or nephrotic syndrome
• Unable to provide consent

Sponsors & Collaborators

• University of Texas at Austin: lead

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Cardiovascular Diseases; Hypertension; Albuminuria

Interventions

Fruit; Vegetables; Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds

Study Officials

• Donald Wesson

  Donald E Wesson Consulting LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2023
• First Posted: September 21, 2023
• Study Start: June 24, 1996
• Primary Completion: November 15, 2006
• Study Completion: December 15, 2011
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 90 days and for 30 days
• Access Criteria: Other medical science investigators