Reducing Dietary Acid With Food Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD)

Dylan MacKay40 enrolled

Overview

Metabolic acidosis is a common problem that occurs with worsening chronic kidney disease. Dietary acid can build up when the kidneys are not working well. This can be associated with a higher risk of worsening kidney function and death. The usual treatment is a medication called sodium bicarbonate which works to balance the acids in the body. The medication however often does not work and causes side effects. Consumption of alkalizing fruit and vegetables may work as a treatment for metabolic acidosis. This trial is being done to see if fruit and vegetables, provided via home delivery, can become a viable management for metabolic acidosis in patients with chronic kidney disease.

Metabolic acidosis is a common complication of advanced chronic kidney disease (CKD). As kidney function declines, the ability to excrete excess dietary acid is reduced. This can lead to the development of metabolic acidosis, an imbalance in the body's acid-base balance. Metabolic acidosis is associated with a higher risk of CKD progression and mortality. Typical treatment includes an oral alkali, such as sodium citrate or sodium bicarbonate. Recent studies have shown that the treatment of metabolic acidosis can reduce the decline in kidney function and potentially prevent progression of CKD to dialysis. Treatment rates with an oral alkali are low because the treatments are ineffective, often poorly tolerated, and may be associated with net harm. Base producing fruit and vegetables are a potential treatment of metabolic acidosis by reducing the dietary contribution to overall acid load that must be managed by the kidneys. A recent systematic review and meta-analysis of clinical trials using oral alkali supplements or reduction in dietary acid intake using fruits and vegetables, when compared to no treatment, usual care or placebo found that these treatments increased serum bicarbonate and slowed the decline of kidney function. Fruit and vegetables are an effective and well-tolerated therapy for the treatment of metabolic acidosis in CKD. While oral alkali therapy has known adverse effects, important limitations also exist in the widespread applicability of fruit and vegetables as a treatment for metabolic acidosis. Only 2 single center randomized trials have examined the efficacy of fruit and vegetables for the management for acidosis. This dual-center trial will be the first randomized trial in Canada to evaluate the feasibility of providing fruit and vegetables via home delivery to patients for the management of metabolic acidosis in CKD. This study will be critical in designing a pan-Canadian phase 3 trial testing the efficacy of alkalizing fruit and vegetable provision on slowing the progression of CKD.

Interventions

Alkalizing Fruit and VegetablesDIETARY_SUPPLEMENT

The weekly deliveries will contain combinations of fresh, frozen, and dried fruits and vegetables, as well as juices and soups which have been selected for their negative potential renal acid load (PRAL) values and shelf-life. All participants will be started at a F+V intake equal to -30 to -40 mEq per day reduction in dietary acid load estimated by the PRAL equation. Participants serum bicarbonate concentration will be measured at 1 month, and at 3 months, those with values \< 22 mEq/L will have their recommended amount of F+V increased to -40 to -50 mEq per day. If a participant's 1- or 3-month serum bicarbonate value exceeds 29 mEq/L, their target dose of F+V in mEq/d will be reduced by 25%.

Sodium bicarbonateDRUG

Study nephrologist will prescribe the oral alkali therapy (sodium bicarbonate) and the medications will be dispensed by the dispensed by the clinic/hospital pharmacies.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the trial * Male or Female, aged 18 years or above * Participants who have an eGFR between 15 and 40 ml/min/1.73m2 * Two consecutive measurements of serum bicarbonate of 14 to 22 mEq/L * Systolic and diastolic blood pressure \<160/100 mmHg * Serum potassium \<5.3 mmol/L * Hemoglobin A1c below ≤ 11% * Are registered in the nephrology clinic in Winnipeg or Halifax * Participants are able to communicate in English and provide written informed consent Exclusion Criteria: * Anuria, dialysis or acute kidney injury/acute kidney failure in the 3 months prior to screening * Chronic obstructive pulmonary disease that requires the participant to be on oxygen * New York Heart Association Class 3-4 Heart failure symptoms or heart, liver or renal transplant * A myocardial infarction or stroke within the last 6 months * Unable to consume study treatments or control, such as swallowing or GI issues * Participants who have participated in another research trial involving an investigational product in the past 12 weeks * Currently on potassium binding therapy * Female participant who is pregnant or on lactating

Outcomes

Primary Outcomes

Randomization to preliminary eligible ratio

Ratio of randomized to preliminary eligible greater, calculated among all patients approached to participate expressed as percentage will be collected at 12 months to investigate fruit and vegetable intervention feasibility. A red, yellow, green framework has been developed as a feasibility metric: green for ratios more than 50%, yellow for ratios 20%-49.9%, and red for ratios less than 20%

Time frame: 12 months

Weekly recruitment rate

Number of new participants per weeks of active recruitment. A green, yellow, red feasibility framework has been developed as a feasibility metric: green for ≥ 0.5 , yellow for 0.125-0.49 and red for \< 0.125

Time frame: 12 months

Study outcome follow up

Study outcome follow up expressed as a percentage, will be calculated at 12 months to investigate the fruit and vegetable intervention feasibility. A red, yellow, green feasibility framework has been developed as a feasibility metric: green for ≥ 95% , yellow for 80%-94.9% and red for \<80%.

Time frame: 12 months

Potential renal acid load (PRAL) in mEq/day

Calculated from average dietary intake assessed by Automated Self-Administered 24-hour Canada (ASA24) dietary recall survey conducted over three days. a red, yellow, green feasibility framework has been developed as a feasibility metric: green for \> 75% , yellow for 50%-75% and red for \<50%.

Time frame: Baseline, 6, and 12 months

Secondary Outcomes

Five repetition chair stand time

the amount of time it takes for a participant to get up out of a chair five times measured in seconds

Time frame: Baseline, 3, 6, 9, and 12 months

Physical function related quality of life

Participants will complete the SF-12 physical component score of the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. The questionnaire is scored between 0-100 with higher values representing physical function related quality of life.

Time frame: Baseline, 3, 6, 9, and 12 months

Serum bicarbonate (total CO2)

Serum bicarbonate concentration in milliequivalents per liter (mEq/L)