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

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

Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure

Metabolic Acidosis in CKD: A Review of Recent Findings

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

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

Metabolic Acidosis and Cardiovascular Disease in CKD

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.

Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR

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) <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<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<0.01), Diltiazem (1.7±7.0 vs. 145.8±36.0 and 153.3±35.7, mg/day, p<0.01), Clonidine (0.14±0.20 vs. 0.65±0.15 and 0.63±0.16, mg/day, p<0.01), Atenolol (0 vs. 6.25±15.1 and 6.25±15.1 mg/day, p<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.

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.

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: Chronic kidney disease (CKD) is a disabling disease with multiple complications, like, increased serum levels of uric acid due to glomerular filtration rate (GFR) impairment. Objectives: This study was designed to evaluate the effect of allopurinol on metabolic acidosis in patients with renal failure. Patients and Methods: This is a randomized controlled-trial study on 50 patients with CKD stage II-IV, who referred to Qaem and Montaserieh hospitals in Mashhad. Patients were selected and randomly divided into two equal groups of 25 subjects. In addition to standard treatments, the intervention group received 100 mg allopurinol tablet for three months and the control group received placebo. Demographic data were obtained from each individual. Serum uric acid level, creatinine, blood pH and bicarbonate levels were assessed at the initiation of treatment and at the end of the third month. Results: The mean age of patients was 54.04±12.62 years. Allopurinol administration resulted in a significant increase of serum bicarbonate levels and pH (P&lt;0.001 for each) compared to the control group. A significant reduction in uric acid (P&lt;0.05) and an increase in GFR (P&lt;0.05) was observed in both groups. Conclusion: Allopurinol could ameliorate metabolic acidosis, glomerular filtration and uric acid in patients with CKD.

Metabolic acidosis becomes increasingly common as chronic kidney disease progresses. It is associated with a number of complications, including bone disease, altered protein synthesis and degradation, skeletal muscle wasting, and lately progressive glomerular filtration rate loss. Experimental and clinical studies suggest a role for alkali therapy to lessen these complications. Recent controlled studies support this notion, and suggest that correction of metabolic acidosis in patients with chronic kidney disease slows the rate of decline of renal function and the development of end-stage renal disease, although more definitive evidence is needed on the long-term benefits of alkali therapy, type of alkali supplements, and the optimal level of serum bicarbonate.

The authors reply:.

Medical Nutrition Therapy for Patients with Non–Dialysis-Dependent Chronic Kidney Disease: Barriers and Solutions