Metabolic Acidosis In Chronic Kidney Disease Research Articles

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol.

Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Adult participants with G3-G5 CKD and metabolic acidosis. Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Hidden Acid Retention with Normal Serum Bicarbonate Level in Chronic Kidney Disease.

Management of metabolic acidosis is crucial for preserving bone, muscle, and renal health, as evidenced by the results of several interventional studies conducted on patients with chronic kidney disease (CKD). Considering the continuity of CKD progression over time, it is reasonable to deduce that a subclinical form of metabolic acidosis may exist prior to the manifestation of overt metabolic acidosis. Covert H+ retention with normal serum bicarbonate level in patients with CKD may result in maladaptive responses that contribute to kidney function deterioration, even in the early stages of the disease. The loss of adaptive compensatory mechanisms of urinary acid excretion may be a key factor in this process. Early modulation of these responses could be an important therapeutic strategy in preventing CKD progression. However, to date, the optimal approach for alkali therapy in subclinical metabolic acidosis in CKD remains uncertain. There is a lack of established guidelines on when to initiate alkali therapy, potential side effects of alkali agents, and the optimal blood bicarbonate levels based on evidence-based practices. Therefore, further research is necessary to address these concerns and establish more robust guidelines for the use of alkali therapy in patients with CKD. Herein, we provide an overview of recent developments on this subject and examine the potential therapeutic approaches that interventional treatments may present for patients with hidden H+ retention, exhibiting normal serum bicarbonate levels - commonly described as subclinical or eubicarbonatemic metabolic acidosis in patients with CKD.

Diagnosing metabolic acidosis in chronic kidney disease: importance of blood pH and serum anion gap.

Metabolic acidosis is one of the most common complications of chronic kidney disease (CKD). It is associated with the progression of CKD, and many other functional impairments. Until recently, only serum bicarbonate levels have been used to evaluate acid-base changes in patients with reduced kidney function. However, recent emerging evidence suggests that nephrologists should reevaluate the clinical approach for diagnosing metabolic acidosis in patients with CKD based on two perspectives; pH and anion gap. Biochemistry and physiology textbooks clearly indicate that blood pH is the most important acid-base parameter for cellular function. Therefore, it is important to determine if the prognostic impact of hypobicarbonatemia varies according to pH level. A recent cohort study of CKD patients showed that venous pH modified the association between a low bicarbonate level and the progression of CKD. Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap. Acidosis with high anion gap frequently develops in later stages of CKD. Therefore, the anion gap is a time-varying factor and renal function (estimated glomerular filtration rate) is a time-dependent confounder for the anion gap and renal outcomes. Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted.

Metabolic Acidosis and Cardiovascular Disease in CKD

Rationale & ObjectiveMetabolic acidosis related to chronic kidney disease (CKD) is associated with an accelerated decline in glomerular filtration rate (GFR) and the development of end-stage kidney disease. Whether metabolic acidosis is associated with cardiovascular (CV) events in patients with CKD is unclear.Study DesignRetrospective cohort study.Setting & ParticipantsThe Optum De-identified Electronic Health Records Dataset, 2007–2017, was used to generate a cohort of patients with non-dialysis-dependent CKD who had at least 3 estimated GFR < 60 mL/min/1.73 m2. Patients with metabolic acidosis (serum bicarbonate 12 to <22 mEq/L) or normal serum bicarbonate (22‒29 mEq/L) at baseline were identified by 2 consecutive measurements 28‒365 days apart.PredictorSerum bicarbonate as a continuous variable.OutcomePrimary outcome was a composite of major adverse cardiovascular events (MACE+). Secondary outcomes included individual components of the composite outcome.Analytical ApproachCox proportional hazards models to evaluate the association between 1-mEq/L increments in serum bicarbonate and MACE+.ResultsA total of 51,558 patients were evaluated, 34% had metabolic acidosis. The median follow-up period was 3.9–4.5 years, depending on the outcome assessed. The adjusted hazard ratio (HR) for MACE+ was 0.964 (95% CI, 0.961–0.968). For the individual components of incident heart failure (HF), stroke, myocardial infarction (MI), and CV death, HRs were 0.98 (95% CI, 0.97–0.98), 0.98 (95% CI, 0.97–0.99), 0.96 (95% CI, 0.96–0.97), and 0.94 (95% CI, 0.93–0.94), respectively, for every 1-mEq/L increase in serum bicarbonate.LimitationsPossible residual confounding.ConclusionsMetabolic acidosis in CKD is associated with an increased risk of MACE+ as well as the individual components of incident HF, stroke, MI, and CV death. Randomized controlled trials evaluating treatments for the correction of metabolic acidosis in CKD to prevent CV events are needed.

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

MO021GALECTIN 3 LEVEL IS REDUCED BY TREATMENT WITH SODIUM BICARBONATE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Circulating cardiac biomarkers implicated in the pathogenesis of heart disease are a non-invasive platform to assess the cardiovascular disease (CVD) burden in individuals with chronic kidney disease (CKD). Galectin 3 is a 26 kDa β-galactoside-binding lectin that has a graded and positive association with CKD stages. In animal models, inhibition of galectin-3 prevents myocardial fibrosis. These pre-clinical findings have not been replicated in randomized controlled studies in humans. Metabolic acidosis of CKD has been shown to be associated with adverse CVD outcomes. We sought to examine whether correction of metabolic acidosis of CKD leads to lower circulating levels of Galectin 3, as an expression of myocardial fibrosis. Method A total of 95 participants with stages 3 and 4 CKD and a serum bicarbonate level between 21-25 mEq/L, were randomized to receive sodium bicarbonate at a dose of 0.4 mEq/kg/day once a day or placebo for two years at two clinical sites in US. Galectin 3, was measured at study baseline and after one year. Results Fifty participants were randomized to sodium bicarbonate and 45 to placebo. Mean age (SD) was 61.4 (10.2) years, 48% were women, 57% were non-Hispanic black, and 40% were non-Hispanic white, 61% had diabetes mellitus and 90% had hypertension at baseline. Mean baseline serum bicarbonate level was 23.5 (SD 1.7), mean (SD) baseline eGFR was 38.8 (11.2) ml/min/1.7m2 and mean (SD) baseline systolic BP was 130 (17) mmHg. There were no differences in baseline characteristics between treatment groups. Compared to the placebo group, participants randomized to sodium bicarbonate had statistically significant change in the levels of Galectin 3 after one year of treatment (-7.12% vs 7.76% and -1.25 vs 1.54 ng/ml, p=0.03 in the sodium bicarbonate vs. placebo group, respectively, Figure). In subgroup analyses by CKD stages, participants with stage 3A randomized to sodium bicarbonate observed the highest decrement in Galectin 3 levels (-19.2% vs 14.7%, p=0.01; -3.3% vs -4.8%, p=0.49; and -7.4% vs 29.1%, p=0.09; for CKD 3B, 3B and 4, respectively). Conclusion The level of Galectin 3 was reduced in patients with CKD 3 and 4 treated with sodium bicarbonate. This provides a framework for future therapeutic interventions aimed at reduction of myocardial fibrosis in patients with CKD and metabolic acidosis.

Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

Abstract P265: Blood Pressure Control is Better and Less Expensive in Chronic Kidney Disease When Associated Metabolic Acidosis is Treated with Fruits and Vegetables Rather Than Sodium Bicarbonate

Background: Both sodium bicarbonate (NaHCO 3 ) and base-producing fruits and vegetables (F+V) improve metabolic acidosis in chronic kidney disease (CKD) and appear to provide similar levels of kidney protection. Because F+V themselves reduce blood pressure, we examined if treatment of metabolic acidosis in CKD with F+V was associated with improved blood pressure control, using fewer anti-hypertensive drugs, and thereby with lower cost of hypertension management. Methods: We randomized 108 subjects with CKD stage 3 eGFR (30-59 ml/min) and metabolic acidosis as follows: F+V (n=36) added to reduce dietary potential renal acid load (PRAL) 50%, oral NaHCO 3 (HCO 3 , n=36) to reduce PRAL 50%, or no alkali (Usual Care, n=36). All were treated toward systolic blood pressure (SBP) &lt;130 mmHg with regimens including ACE inhibition and followed 5 years. Results: Entry SBP and initial doses of 5 formulary anti-hypertensive drugs most commonly used for blood pressure control in CKD were not different among the 3 groups. At 5 years, SBP was lower in F+V (125±5 mm Hg) than both HCO 3 and Usual Care (135±5 and 134±5 mm Hg, respectively, p&lt;0.01 vs. F+V for each). Daily doses for the following drugs at year 5 were lower in F+V than HCO 3 and Usual Care: Enalapril (8.3±2.4 vs. 11.1±3.6 and 11.7±4.8, mg/day, respectively, p&lt;0.01), Diltiazem (1.7±7.0 vs. 145.8±36.0 and 153.3±35.7, mg/day, p&lt;0.01), Clonidine (0.14±0.20 vs. 0.65±0.15 and 0.63±0.16, mg/day, p&lt;0.01), Atenolol (0 vs. 6.25±15.1 and 6.25±15.1 mg/day, p&lt;0.02) but there was no difference among groups in the year 5 dose of hydrochlorthiazide (16.1±9.9 vs. 21.9±16.2 and 21.5±16.3 mg/day, p=0.27). Five-year drug cost of hypertension management was less in F+V ($79,760) than both HCO 3 ($155,372) and Usual Care ($152,305). Conclusions: Treating metabolic acidosis in CKD patients with F+V but not NaHCO 3 was associated with lower SBP, use of fewer and lower doses of anti-hypertensive drugs, and lower group cost of hypertension management. The data support that clinicians consider these adjunctive benefits of F+V on hypertension management when recommending treatment strategies for metabolic acidosis in CKD.

Approach to the Treatment of Chronic Metabolic Acidosis in CKD

Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered.

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

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.

1H NMR-Based Metabolite Profiling of Plasma in a Rat Model of Chronic Kidney Disease

Chronic kidney disease (CKD) is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. 1H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx)), particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx) compared to sham-operated rats. Principle components analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2)n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids.

The role of metabolic acidosis in chronic kidney diseases

AbstractBackground and objectives: This review focuses on three areas, basic acid-base physiology especially concerning hydrogen ion balance, development of acidosis in chronic kidney disease (CKD), and the consequences of acidosis. We highlight what is well established, what is less certain, and what is unknown. Method and results: The literature on acidosis in CKD were searched from 2004 to 2010 utilizing PubMed, Google Scholar, and Ovid to augment the classic work on acid base physiology over the past three decades. The original research in endogenous acid production and net acid excretion were reviewed. Touching upon the development of metabolic acidosis in CKD, we focused on the consequences of chronic metabolic acidosis on growth and other important variables. Finally, we recognize the significant issue of patients’ medical non-compliance and presented treatment strategy to counter this problem. Conclusion: The correction of acidosis in chronic kidney disease needs no advocacy. The case is made conclusively. Patient non-compliance because of the medication that needs to be taken several times a day is a problem, requiring due diligence.