Alkali Therapy for Kidney Complication
Recruiting in Palo Alto (17 mi)
Overseen byJessica Kendrick, MD MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Colorado, Denver
Must be taking: Immunosuppressants
Must not be taking: Anticoagulants, Alkali therapy
Disqualifiers: Heart failure, Uncontrolled hypertension, others
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Lower serum bicarbonate levels, even within the normal laboratory range, in kidney transplant recipients (KTRs) are associated with an increased risk of graft loss, cardiovascular events and mortality. Because acid retention is common in KTRs, it is plausible that alkali therapy in KTRs may also result in improved vascular and graft function. The investigators will perform a randomized, double-blinded, placebo-controlled, 12 month study in 120 KTRs to examine the effect of sodium bicarbonate therapy on surrogate markers of CVD and graft function. The overall hypothesis is that treatment with bicarbonate will improve indicators of vascular and graft function in KTRs by decreasing complement activation.
Do I need to stop my current medications for the trial?
The trial does not specify if you need to stop your current medications, but you must have a stable immunosuppression and anti-hypertensive regimen before joining. You cannot take medications that interact with the trial's agents, like sildenafil with nitroglycerin.
What data supports the effectiveness of the drug sodium bicarbonate for kidney complications?
Research shows that sodium bicarbonate can help protect kidney function in people with chronic kidney disease and acute kidney injury by correcting acid imbalance and preventing further damage.
12345Is alkali therapy, like sodium bicarbonate, safe for humans?
Sodium bicarbonate is generally safe for humans, but excessive use can lead to problems like high blood pressure, muscle breakdown, and kidney issues. Most people don't experience these problems, but it's important to use it as directed by a healthcare provider.
14678How is the drug sodium bicarbonate unique in treating kidney complications?
Sodium bicarbonate is unique because it helps correct acid levels in the body, which can preserve kidney function in chronic kidney disease (CKD) patients. Unlike other treatments, it specifically targets metabolic acidosis (a condition where the body produces too much acid or the kidneys cannot remove enough acid) and may reduce harmful substances like angiotensin II that can damage the kidneys.
1491011Eligibility Criteria
This trial is for kidney transplant recipients aged 18-80 with stable health, not on conflicting meds or treatments, and a BMI under 40. They should have had their transplant at least a year ago, be on specific immunosuppressants, and have certain levels of serum bicarbonate and eGFR—a measure of kidney function.Inclusion Criteria
Your body mass index (BMI) is less than 40 kg/m2.
Your blood test results show a normal level of bicarbonate on two different days.
Your kidney function, measured by eGFR, needs to be at least 45 ml/min/1.73m2.
+8 more
Exclusion Criteria
I regularly use supplemental oxygen.
I have not taken daily oral alkali like baking soda in the last 3 months.
I am currently taking blood thinners.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sodium bicarbonate or placebo for 12 months to assess effects on vascular and graft function
12 months
Regular visits for monitoring and assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests if sodium bicarbonate can improve heart and graft health in those who've received a kidney transplant. It's a double-blind study where half the participants will get sodium bicarbonate and the other half a placebo for one year to compare effects.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Sodium bicarbonateExperimental Treatment1 Intervention
Oral sodium bicarbonate at a dose of 0.5 mEq/kg-lean body weight/day
Group II: PlaceboPlacebo Group1 Intervention
Oral placebo at a dose of 0.5 mEq/kg-lean body weight/day
Sodium bicarbonate is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Sodium bicarbonate for:
- Metabolic acidosis
- Antacid
- Heartburn relief
🇪🇺 Approved in European Union as Sodium bicarbonate for:
- Metabolic acidosis
- Antacid
🇨🇦 Approved in Canada as Sodium bicarbonate for:
- Metabolic acidosis
- Antacid
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of ColoradoAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial. [2021]Label="BACKGROUND">Oral sodium bicarbonate (NaHCO3) may preserve kidney function in CKD, even if initiated when serum bicarbonate concentration is normal. Adequately powered trials testing this hypothesis have not been conducted, partly because the best dose for testing is unknown.
The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis. [2019]The aim of this meta-analysis was to explore the efficacy of sodium bicarbonate in preventing contrast-induced nephropathy (CIN).
Effect of sodium bicarbonate preloading on ischemic renal failure. [2022]Rats pretreated with sodium bicarbonate were functionally protected from the damage of bilateral renal artery occlusion. The rise in serum creatinine (day 1 minus day 0) during the first 24 h after ischemia was 2.88 +/- 0.28 mg% in the bicarbonate-loaded animals versus 3.90 +/- 0.26 mg% in their matched controls (p less than or equal to 0.01). Pretreatment with acetazolamide produced a similar alkaline urine as the bicarbonate loading (pH 8.3 vs. 7.0 in controls) and a similar degree of protection (delta creatinine 2.85 +/- 0.41 vs. 4.23 +/- 0.26 mg%; p less than or equal to 0.01). A direct effect of sodium loading was excluded by comparing NH4HCO3 with NaHCO3 loading and observing no difference in delta creatinine levels after ischemia (3.39 +/- 0.69 vs. 3.20 +/- 0.61 mg%). These data indicate that NaHCO3 protects in this model of acute renal failure and further suggest that the mechanism of protection is not related to either systemic alkalosis or sodium loading.
Short- and long-term effects of alkali therapy in chronic kidney disease: a systematic review. [2021]Clinical practice guidelines recommend alkali therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and metabolic acidosis to prevent complications from metabolic acidosis. We systematically reviewed the effect of sodium bicarbonate on benefits and harms in patients with CKD.
Sodium bicarbonate supplements for treating acute kidney injury. [2023]Acute kidney injury (AKI) is a common, serious, but potentially treatable condition. Because AKI is often associated with acidosis, it has become common practice to recommend administration of sodium bicarbonate to correct acid imbalance.
Acute toxicity from baking soda ingestion. [2019]Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.
Is bicarbonate therapy effective in preventing CKD progression? [2022]YES. Long-term sodium bicarbonate therapy slightly slows the loss of renal function in patients with chronic kidney disease (CKD) and may moderately reduce progression to end-stage renal disease (strength of recommendation [SOR]: B, meta-analyses of lower-quality randomized controlled trails [RCTs]). Therapy duration of 1 year or less may not be beneficial (SOR: C, secondary analyses in meta-analyses).
Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report. [2021]We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.
Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. [2022]Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.
Comparison potassium sodium hydrogen citrate with sodium bicarbonate in urine alkalization: a prospective crossover-controlled trial. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">Excessive alkalization will increase the incidence of nephrolithiasis. Sodium bicarbonate (NaHCO3) and potassium sodium hydrogen citrate (PSHC) are commonly used drugs for urinary alkalization. We designed a trial to compare PSHC with NaHCO3 in the urine alkalization for the Chinese healthy participants and to explore the effects of PSHC and NaHCO3 on circadian rhythms of urine pH value.
The Effects of Oral Sodium Bicarbonate on Renal Function and Cardiovascular Risk in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. [2023]Oral sodium bicarbonate is often used to correct acid-base disturbance in patients with chronic kidney disease (CKD). However, there is little evidence on patient-level benign outcomes to support the practice.