Effects of a Low-PRAL Modified New Nordic Renal Diet on Acid-Base Status in Patients With Stage 4-5 Chronic Kidney Disease and Chronic Metabolic Acidosis.

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.

A Decade After the KDOQI CKD Guidelines: Impact on the United States and Global Public Policy

Hyperphosphatemia and metabolic acidosis are frequently encountered in advanced chronic kidney disease (CKD) patients. Correction of metabolic acidosis in patients with advanced CKD leads to a decrease in the progression of renal impairment and improves nutritional outcomes. Lanthanum carbonate is used for control of hyperphosphatemia. This study evaluated the effect of lanthanum carbonate on metabolic acidosis in CKD IV-V patients and in patients on dialysis. Retrospective data of patients in whom lanthanum carbonate therapy was initiated were collected from 2009 to 2013 in a single dialysis center. Of the 79 patients in whom lanthanum carbonate was introduced, 51 patients were included in the analysis. Of the 51 patients, 39 patients received chronic hemodialysis, two patients received peritoneal dialysis therapy, and 10 patients had stage IV-V CKD not on dialysis. The primary outcome was the serum bicarbonate change after the introduction of lanthanum carbonate. There was a significant increase in mean serum bicarbonate concentration of 2.79 mmol/L (p ≤ 0.001) compared to baseline. The increase remained in the CKD IV-V patients (2.50 mmol/L, p = 0.005) and in the patients on dialysis (2.81 mmol/L, p < 0.001). Serum bicarbonate remained higher (p > 0.05) than baseline up to 6 months after lanthanum carbonate introduction. In this study, lanthanum carbonate introduction increased serum bicarbonate concentration in a small sample of CKD IV-V patients and in patients on dialysis. Further studies are needed to confirm this effect and investigate whether the correction of metabolic acidosis by using lanthanum carbonate in CKD IV-V patients can improve clinical outcomes.

ANTICOAGULATION FOR ATRIAL FIBRILLATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGES 4 AND 5, NOT ON DIALYSIS

Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial

Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.

Introduction: Metabolic acidosis is commonly encountered in chronic kidney disease (CKD) which contributes to its progression. The metabolic acidosis in chronic kidney disease is presumed to be due to accumulation of unmeasured anions leading to a high anion gap (AG). The aim of the study was to assess the metabolic acidosis in renal failure patients using the calculation of delta gap. Methods: 100 renal failure cases were included. Their abnormal urea and creatinine values were utilized to calculate the BUN/creatinine ratio for all the cases. Based on the dipstick urine testing grading, proteinuric renal diseases were identified. The urine and serum osmolality were calculated in these renal failure patients. Serum osmolality was calculated using the values of serum sodium and urea. Urinary density which is also called urine specific gravity was used for indirect calculation of urine osmolality. Modified delta gap equation was applied for quick evaluation of mixed metabolic acid-base disorders. Results: Out of the 100 cases, 41 were proteinuric renal disease cases and 59 were non-proteinuric renal disease cases. High anion gap metabolic acidosis were seen in 65% of the total 100 cases. In 33% of the total cases, non-anion gap metabolic acidosis was also seen in addition to the high anion gap metabolic acidosis as it is evidenced by the delta gap value of less than -6 mmol/L. Conclusions: Earlier identification of the type and causative mechanism of metabolic acidosis in these patients may help to decrease the morbidity and mortality of these patients. The delta gap that can be easily calculated using this quick and short equation at the bedside may serve as a marker in the management of metabolic acidosis in renal failure patients. Keywords: delta gap; modified quick equation; metabolic acidosis; renal failure

Background: Metabolic acidosis is a common complication in patients with chronic kidney disease (CKD) that accelerates disease progression and worsens overall health outcomes. Objective: This study compares the safety and effectiveness of sodium citrate and sodium bicarbonate in treating metabolic acidosis in CKD patients to determine the optimal therapeutic approach. Method: A prospective randomized clinical trial was conducted at the Department of Anesthesiology and ICU, Shaheed Monsur Ali Medical College and Hospital, Dhaka, Bangladesh, from October 2023 to September 2024. A total of 132 CKD patients with metabolic acidosis were randomly assigned to two groups: Group A (66 patients) received sodium citrate, and Group B (66 patients) received sodium bicarbonate. Safety, efficacy, and acid-base balance were monitored over 12 months. Results: Both sodium citrate and sodium bicarbonate significantly improved serum bicarbonate levels and reduced blood acidity. In Group A, 85% of patients showed a 50% reduction in acidemia, compared to 78% in Group B. However, Group A demonstrated superior gastrointestinal tolerance (10% side effects) compared to Group B (25% side effects). Sodium citrate also improved bone health markers, with a 15% improvement in calcium levels, while sodium bicarbonate patients had a 10% increase. However, sodium bicarbonate was more cost-effective. Conclusions: Sodium citrate appears to be more effective and better tolerated than sodium bicarbonate in treating metabolic acidosis in CKD patients, though cost considerations may influence therapeutic choices.

Current management of metabolic acidosis in patients with chronic kidney disease (CKD) relies on dietary intervention to reduce daily endogenous acid production or neutralization of retained acid with oral alkali (sodium bicarbonate, sodium citrate). Veverimer is being developed as a novel oral treatment for metabolic acidosis through removal of intestinal acid, resulting in an increase in serum bicarbonate. Veverimer is a free-amine polymer that combines high capacity and selectivity to bind and remove hydrochloric acid (HCl) from the gastrointestinal (GI) tract. In vitro studies demonstrated that veverimer had a binding capacity of 10.7 ± 0.4 mmol HCl per gram of polymer with significant binding capacity (>5 mmol/g) across the range of pH values found in the human GI tract (1.5-7). Upon protonation, veverimer bound chloride with high specificity but showed little or no binding of phosphate, citrate, or taurocholate (<1.5 mmol/g), which are all anions commonly found in the human GI tract. Administration of veverimer to rats with adenine-induced CKD and metabolic acidosis resulted in a significant increase in fecal chloride excretion and a dose-dependent increase in serum bicarbonate to within the normal range compared with untreated controls. Absorption, distribution, metabolism, and excretion studies in rats and dogs dosed with 14C-labeled veverimer showed that the polymer was not absorbed from the GI tract and was quantitatively eliminated in the feces. Acid removal by veverimer, an orally administered, nonabsorbed polymer, may provide a potential new treatment for metabolic acidosis in patients with CKD. SIGNIFICANCE STATEMENT: Metabolic acidosis is a complication of chronic kidney disease (CKD) as well as a cause of CKD progression. Veverimer is a high-capacity, selective, nonabsorbed, hydrochloric acid-binding polymer being developed as a treatment for metabolic acidosis. Veverimer binds and removes hydrochloric acid from the gastrointestinal tract, resulting in increased serum bicarbonate and the correction of metabolic acidosis. Veverimer is not an ion-exchange resin and does not deliver sodium or other counterions, and so it may be appropriate for patients with CKD with and without sodium-sensitive comorbidities.

BackgroundMetabolic acidosis is a complication of chronic kidney disease (CKD) that increases risk of CKD progression, and causes bone demineralization and muscle protein catabolism. Patients with diabetes are prone to metabolic acidosis and functional limitations that decrease quality of life. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. This post hoc subgroup analysis evaluated effects of veverimer on metabolic acidosis and physical function among patients with diabetes.MethodsThis was a Phase 3, multicenter, randomized, blinded, placebo-controlled trial in 196 patients with CKD (estimated glomerular filtration rate 20–40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo.ResultsAt Week 52, veverimer-treated patients with diabetes (n = 70), had a significantly greater increase in mean serum bicarbonate than the placebo group (n = 57) (4.4 versus 2.9 mmol/L, P < 0.05). Patient-reported limitations of physical function on the Kidney Disease and Quality of Life-Physical Function Domain (e.g. walking several blocks and climbing a flight of stairs) improved significantly in the veverimer versus placebo group (+12.5 versus +0.3, respectively, P < 0.001) as did objective physical performance on the repeated chair stand test (P < 0.0001).ConclusionsFew interventions for patients with diabetes and CKD have successfully improved quality of life or physical functioning. Our study demonstrated that veverimer effectively treated metabolic acidosis in patients with diabetes and CKD, and significantly improved how these patients felt and functioned.

ObjectiveThis study aimed to (i) compare the extent of urinary potassium (K+) excretion in addition to the changes in serum K+ concentration: and (ii) clarify the association between changes in serum K+ concentration, urinary K+ excretion, and acid-base status with or without renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with advanced chronic kidney disease (CKD) stages.MethodsSix hundred and ninety-one patients with advanced CKD (CKD G3b, 161; G4, 271; G5, 259) were retrospectively evaluated. Differences in serum K+ concentration, urinary K+ excretion, and serum sodium and chloride differences (Na+−Cl-) were compared among patients with RAAS inhibitors, RAAS inhibitors and diuretic agents, and without either medication in each CKD stage.ResultsSerum K+ concentrations in patients with RAAS inhibitors were significantly higher than in those with RAAS inhibitors and diuretics in CKD stage G3b and the other two treatment groups in CKD stage G4. Urinary K+ excretion among the three groups did not differ significantly in each CKD stage. Serum Na+−Cl- differences in patients with RAAS inhibitors were significantly smaller than in those with RAAS inhibitors and diuretics in CKD stages G3b (p = 0.006) and the other two groups in CKD stage G4 (vs. RAAS inhibitors and diuretics, p <0.001; vs. without either medication, p = 0.008).ConclusionOur study demonstrated that RAAS inhibitor use might be associated with hyperkalemia via not decreased urinary K+ excretion but rather K+ redistribution from intracellular to extracellular fluid induced by the progression of metabolic acidosis in patients with advanced CKD, particularly stages G3b and G4.

Metabolic acidosis is commonly found in patients with chronic kidney disease (CKD), and its causes are: impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food. As the consequence, numerous metabolic abnormalities develop, which may lead to dysfunction of several organs. In observational studies, it has been found that CKD patients with metabolic acidosis are characterised by faster progression of kidney disease towards end stage kidney failure, and by increased mortality. Results of interventional studies suggest that alkali therapy in CKD patients slows progression of kidney disease. In view of these facts, the members of “The Working Group of the Polish Society of Nephrology on Metabolic and Endocrine Abnormalities in Kidney Diseases” have prepared the following statement and guidelines for the diagnosis and treatment of metabolic acidosis in CKD patients. Measurement of bicarbonate concentration in venous plasma or venous blood to check for metabolic acidosis should be performed in all CKD patients and metabolic acidosis in these patients should be diagnosed when the venous plasma or venous blood bicarbonate concentration is lower than 22 mmol/l. In patients with metabolic acidosis and CKD, oral sodium bicarbonate administration is recommended. The goal of such a treatment is to achieve a plasma or blood bicarbonate concentration equal to or greater than 22 mmol/l.

Background: Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. Summary: Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. Key Message: The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

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Person-Centered Kidney Education: The Path Forward