Metabolic Acidosis In Hemodialysis Patients Research Articles

Effects of Oral Sodium Bicarbonate Supplementation on Protein Metabolism and Inflammation in Iraqi Hemodialysis Patients: An Open-Label Randomized Controlled Trial.

The effect of correcting metabolic acidosis on protein metabolism in hemodialysis patients is controversial. To study the effects of oral sodium bicarbonate on protein metabolism and markers of inflammation in acidotic hemodialysis patients. Patients and Methods. An open-label randomized controlled trial was conducted at a single center. Sixty-six clinically stable adult hemodialysis patients were recruited with an average predialysis serum bicarbonate level of <22 mmol/l and a dialysate bicarbonate concentration of 35 mmol/l. Forty-nine participants have completed the study. Oral sodium bicarbonate tablets of 500 mg were given daily in the intervention group (n = 25) for 12 weeks versus the standard of care in the control group (n = 24). Outcomes compared intervention versus nonintervention in both groups at equivalent time points (0 and 3 months). The clinical data, anthropometry, dialysis adequacy, albumin, normalized protein catabolism rate, blood gas analysis, and bicarbonate were recorded at 0 and 3 months. In addition, muscle mass and handgrip strength were measured. Finally, IL-6 as a marker of inflammation was measured at randomization and three months. Serum bicarbonate and pH increased significantly from 17.57 ± 3.34 mmol/L to 20.69 ± 2.54 mmol/L and from 7.26 ± 0.06 to 7.34 ± 0.04, respectively (p < 0.0001). Serum albumin was significantly higher in the intervention group at three months than in the control group, 4.11 ± 0.45 vs. 3.79 ± 0.47 (p value 0.011). Serum potassium significantly decreased in the intervention group at three months compared to the control group, 5.00 ± 0.43 mEq/l vs. 5.33 ± 0.63 mEq/l (p value 0.03). Muscle strength expressed as handgrip has improved significantly in the intervention group at three months compared to the control group, 45.01 ± 19.19 vs. 33.93 ± 15.06 (p value 0.03). The IL-6 values were less in the intervention group at 3 months with a p value of 0.01. The interdialytic weight of the intervention group at three months was 2.42 ± 0.64 compared to the 2.20 ± 1.14 control group, but this did not reach statistical significance (p value of 0.4). The composite of (albumin + nPCR) at three months was achieved in 59.18% of the intervention group compared to 14.28% with a p value of 0.01. Correcting metabolic acidosis in hemodialysis patients improved serum albumin and nPCR without hypokalemia or significant interdialytic weight gain. This was particularly evident in patients with minimal inflammation with low IL-6 values.

Effects of pre-analytical sample care and analysis methodology on measures of metabolic acidosis in hemodialysis patients.

We evaluated the effects of pre-analytical care on total carbon dioxide (tCO2 ) in hemodialysis patients, as calculated by blood gas analysis (ctCO2 ) or measured by an enzymatic assay (mtCO2 ). Blood samples were collected via vascular access before dialysis sessions. For blood gas analysis, eight aliquots were collected, refrigerated or non-refrigerated, and analyzed at 0, 4, 8, and 24 h after collection. A blood sample was then collected for the enzymatic method and distributed into 14 aliquots. Half of the aliquots were refrigerated. The samples analyzed at time point 0 were centrifuged immediately. The remaining aliquots of both the refrigerated and non-refrigerated clusters were centrifuged before storage. Samples were analyzed at 4, 8, and 24 h post-collection. By blood gas analysis, no significant change was found in bicarbonate values over time, either in the non-refrigerated or refrigerated samples. ctCO2 values during the experiment showed a minor but statistically significant increase of questionable clinical relevance in both non-refrigerated and refrigerated aliquots. In the enzymatic assay, the reduction in mtCO2 levels during the experiment was negligible. The median absolute reductions at the end of the experiment were 1.77, 1.21, 1.04, and 1.12 mmol/L for the non-centrifuged/non-refrigerated, centrifuged/non-refrigerated, non-centrifuged/refrigerated, and centrifuged/refrigerated aliquots, respectively. Our results suggest that measured or calculated tCO2 levels of capped and cooled samples are adequate for analyzing the acid-base status of hemodialysis patients, even when such determination is not performed immediately after collection.

Treatment of Metabolic Acidosis in Hemodialysis Patients Is Biased by Type of Vascular Access

Considerable debate exists about the optimal treatment of metabolic acidosis in hemodialysis patients,1,S1,S2 and interventional studies evaluating the effect of different target predialysis bicarbonate levels on outcomes are lacking. Observational studies have found somewhat conflicting results regarding the correlation of predialysis bicarbonate levels with cardiovascular and all-cause mortality but mostly pointed to a U-shaped relationship after adjustment for confounding factors.2–6 On the basis of these observational studies, guidelines have formulated target predialysis serum bicarbonate levels.

Metabolic acidosis in hemodialysis patients: a review

Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is associated with increased mortality and its deleterious effects are already present in the predialysis phase of chronic kidney disease. Metabolic acidosis has been linked to progression of chronic kidney disease, changes in protein and glucose metabolism, bone and muscle disorders and cardiovascular disease. At present, the control of metabolic acidosis in hemodialysis is mainly focused on the supply of bicarbonate during dialysis session, but further studies are needed to set the optimum target serum bicarbonate and the best concentration of the bicarbonate dialysate. The present study reviews pathophysiological and epidemiological aspects of metabolic acidosis in hemodialysis patients and also addresses its adverse effects and treatment.

The evaluation of the relationship between serum levels of Interleukin-6 and Interleukin-10 and metabolic acidosis in hemodialysis patients.

Chronic kidney disease is defined as progressive kidney dysfunction. The levels of various cytokines increase in hemodialysis (HD) patients. High levels of interleukins (ILs) and presence of metabolic acidosis are described as independent risk factors for morbidity and mortality in these patients. This study was designed to evaluate the relationship between IL-6 and IL-10 and serum bicarbonate and metabolic acidosis in HD patients. In this analytical crosssectional study, patients referred to the HD units of Loghman Hakim and Shahid Ashrafi Esfahani Hospitals were randomly selected. Demographic and laboratory data, such as albumin, creatinine, calcium, phosphorus, parathormone, C-reactive protein, complete blood count, ferritin, ILs-6 and -10, and arterial blood gas analysis, were recorded for each patient. The correlation between IL and serum bicarbonate and other variables were evaluated by SPSS software. The patients were compared for the presence of acidosis and positivity for IL. A total of 84 patients with a mean age of 60.98 years and mean body mass index of 24.86 kg/m[2] were evaluated (53% male and 57% female). The mean dialysis duration was 24.86 ± 3.98 months. Overall, 41.7% of the patients had diabetes mellitus and 36.9% of them had hypotension. The mean serum levels of IL-6 and IL-10 were 6.036 and 17.46 pg/ml, respectively. There was a significant correlation between IL-6 and IL-10 levels and serum bicarbonate and the incidence of metabolic acidosis (P <0.05). Based on the results, metabolic acidosis and bicarbonate could be considered prognostic factors to differentiate the increased levels of IL-6 and IL-10 and associated morbidity and mortality.

Effect of chloride dialysate concentration on metabolic acidosis in aintenance hemodialysis patients

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

塩酸セベラマー内服量が血液透析患者の酸塩基平衡に及ぼす影響―クエン酸透析液使用でも，代謝性アシドーシスを悪化させるか？―

塩酸セベラマー内服量が血液透析患者の酸塩基平衡に及ぼす影響―クエン酸透析液使用でも，代謝性アシドーシスを悪化させるか？―

Efeito benéfico da correção da acidose metabólica no estado nutricional de pacientes em hemodiálise

OBJETIVO: Avaliar o efeito da correção da acidose metabólica no estado nutricional de pacientes em hemodiálise. MÉTODOS: Foram estudados, durante seis meses, 20 pacientes com acidose metabólica, definida pela média de três mensurações de bicarbonato sérico pré-diálise < 22 mEq/L. Os pacientes dialisavam há, pelo menos, seis meses, utilizando bicarbonato de 35 mEq/L no dialisato. A correção da acidose metabólica foi feita mediante elevação do bicarbonato no dialisato para valores que não ultrapassaram 40 mEq/L, objetivando um bicarbonato sérico entre 22-26 mEq/L. Foram avaliados no início e no final do estudo: avaliação antropométrica, dietética, bioquímica e Avaliação Subjetiva Global (ASG). RESULTADOS: A avaliação nutricional na fase inicial do estudo demonstrou índice de massa corporal normal (24,23 ± 3,83 kg/m²). A circunferência muscular do braço, a prega cutânea tricipital e a ASG classificaram homens e mulheres como desnutridos. Os consumos de calorias e proteínas foram 29,7 ± 10,1 kcal/kg/dia e 1,31 ± 0,35 g/kg/dia, respectivamente. A avaliação bioquímica observou albumina sérica normal e colesterol reduzido. Após correção, bicarbonato sérico e pH aumentaram de 18,2 ± 1,64 para 22 ± 1,70 (p < 0,001), e de 7,32 ± 0,45 para 7,37 ± 0,41 (p < 0,001), respectivamente. Houve melhora da ASG (21,7 ± 6,4 versus 16,8 ± 6,6, p < 0,001) e aumento na ingestão calórica (1.892,61 ± 454,30 versus 2.110,30 ± 869,24, p < 0,05). CONCLUSÃO: A suplementação de bicarbonato na solução de hemodiálise foi método efetivo para a correção da acidose metabólica, determinando aumento da ingestão calórica e melhora nos escores da ASG.

Correction of Metabolic Acidosis on Serum Albumin and Protein Catabolism in Hemodialysis Patients

The effect of the correction of metabolic acidosis (MA) on serum albumin concentrations (sAlbs) in hemodialysis (HD) patients is controversial. This study evaluated the role of the correction of MA on sAlb concentrations, normalized protein catabolic rate (nPCR), and the effect of the concomitant inflammatory status, in a group of acidotic HD patients. The correction of MA by oral supplementation with sodium bicarbonate, and the evaluation of its effect on sAlb, nPCR, and high-sensitivity C-reactive protein (hsCRP), were performed in 29 patients on bicarbonate dialysis for a median of 30 months. Other variables included pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, body weight, interdialytic weight gain, pre-HD systolic and diastolic blood pressure, and Kt/V. Serum bicarbonate and pH increased significantly (P < .0001), from 19.1 +/- 0.7 mmol/L to 24.6 +/- 1.1 mmol/L and from 7.33 +/- 0.03 to 7.39 +/- 0.02, respectively (all values with +/- are SD). The nPCR decreased from 1.13 +/- 0.14 g/kg/day to 1.05 +/- 0.14 g/kg/day (P < .0001). The other variables did not change significantly. In 17 patients with high-sensitivity C-reactive protein <10 mg/L, sAlb increased from 3.7 +/- 0.3 g/dL to 4.0 +/- 0.3 g/dL (P < .01), whereas in 12 with high-sensitivity C-reactive protein >or=10 mg/L, sAlb did not change (3.5 +/- 0.17 g/dL vs. 3.4 +/- 0.13 g/dL; P = NS). Oral sodium bicarbonate supplementation is effective in correcting MA in HD patients and does not affect interdialytic weight gain, plasma Na, and blood pressure. The correction of MA is effective in reducing protein catabolism (nPCR) in both inflamed and less inflamed HD patients, but increases sAlb only in patients without inflammation. In inflamed patients, the correction of MA is not sufficient per se to improve sAlb concentrations.

A Review Article: Sevelamer Hydrochloride and Metabolic Acidosis in Dialysis Patients

Sevelamer hydrochloride is a phosphate binder and its effectiveness to reduce the cardiovascular mortality of dialysis patients has been tested. Sevelamer hydrochloride also contains chlorine, so a decrease in bicarbonate due to chlorine load was anticipated and metabolic acidosis thought to associate with sevelamer hydrochloride has been reported in some papers. We reported that sevelamer hydrochloride exacerbated metabolic acidosis in hemodialysis patients, depending on the dosage. Also a Japanese nationwide survey suggested that sevelamer hydrochloride usage potentially aggravates acidosis in dialysis patients. A multi-institute research study by Edmung et al. has shown that metabolic acidosis, with serum CO2 below 17.5 mmol/L, is by itself associated with increased risk of death in dialysis patients. Furthermore, the Dialysis Outcomes and Practice Patterns Study (DOPPS) revealed that both high (> 27 mmol/L) and low (< or = 17 mmol/L) serum bicarbonate (total CO2) levels were associated with increased risk for mortality and hospitalization. There has not been any significant evidence to show that sevelamer hydrochloride has reduced the cardiovascular mortality of dialysis patients compared with calcium-based binder. Clinicians should check not only the level of chlorine but also the level of total CO2 or bicarbonate during the treatment with sevelamer hydrochloride, and control metabolic acidosis.

Sevelamer Hydrochloride Exacerbates Metabolic Acidosis in Hemodialysis Patients, Depending on the Dosage

Sevelamer hydrochloride, as a phosphate binder that contains neither aluminum nor calcium, is expected to improve the prognosis of dialysis patients. However, sevelamer hydrochloride has been reported to lower the serum bicarbonate level. In the present study, we performed a retrospective study on the potential influences of sevelamer hydrochloride on metabolic acidosis in hemodialysis patients. The subjects were 72 patients who underwent hemodialysis at our hospital. Thirty-six patients taking sevelamer hydrochloride and 36 patients matched for sex, diabetes mellitus, age and duration of dialysis who were not taking sevelamer hydrochloride were studied. We assigned the 36 patients who had been taking sevelamer hydrochloride to the 'sevelamer group', and the 36 patients not taking sevelamer hydrochloride were the control group. Statistical significance was evaluated by a t-test and Pearson's correlation coefficient. In the sevelamer group, the mean levels of bicarbonate, base excess and pH decreased significantly after administration, compared with the values before administration, but in the control group, aggravation of acidosis was not seen. The levels of bicarbonate, base excess and pH after the medication of sevelamer hydrochloride were found to be significantly and negatively correlated with the daily dose of sevelamer hydrochloride. The levels were also found to be significantly and negatively correlated with the cumulative dose of sevelamer hydrochloride; however, the value of the mean levels of chlorine and the anion gap did not increase with sevelamer hydrochloride. Sevelamer hydrochloride caused metabolic acidosis in a dose-dependent manner in hemodialysis patients without hyperchloremia.

Spurious metabolic acidosis in hemodialysis patients

Metabolic acidosis with an increased anion gap (AG) is frequently seen among patients with end-stage renal failure that is corrected to a variable degree by chronic hemodialysis. The degree of acidosis is generally interpreted from the concentration of total carbon dioxide (tCO2 ) in blood drawn from the vascular access used for dialysis. As with many dialysis units in the United States, our laboratory studies for outpatients are performed in a central laboratory several hundred miles away and must be shipped there by air freight. We observed a consistent and clinically important difference between the tCO2 content of samples reported from the central laboratory compared with results reported from a local university hospital chemistry laboratory. The central laboratory readings were always lower, resulting in an increase in the AG. Delays in centrifugation of the blood to separate the clot from the serum and in the initiation of analysis led to an increase in the lactate content of the samples. That increase, however, was insufficient to explain the difference in tCO2 levels. These data suggest that something happens to the samples in transit to cause an artifactual reduction of the tCO2 level. For many dialysis patients, the severity of their acidosis may be falsely represented by the tCO2 content of blood samples reported from central laboratories.

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium.

Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium. In this study, the parathyroid response to the correction of acidosis in eight hemodialysis patients was determined by performing dynamic assessment of parathyroid function before and after the correction of acidosis. The parathyroid response to intravenous calcitriol before and after the correction of acidosis was also assessed. After optimal correction of acidosis, there were no significant changes in blood pH, ionized calcium, phosphate, or alkaline phosphatase values, but the level of venous total CO2 increased significantly. Parathyroid hormone/ionized calcium curves were displaced downward after correction of acidosis, but not after the administration of intravenous calcitriol. The correction of metabolic acidosis in hemodialysis patients with secondary hyperparathyroidism can suppress parathyroid hormone secretion by increasing the sensitivity of the parathyroid glands to ionized calcium.

Metabolic acidosis and nutrition in dialysis patients.

The renal elimination of nonvolatile acids, mainly formed by oxidation of sulfuric amino acids, is about 70 mmol/day. In hemodialysis (HD) patients who cannot eliminate an excess of H+ via the kidneys, the accumulation of H+ in the interdialytic period results in progressive depletion of the bicarbonate buffer stores, which are repleted by the dialysis procedure. Metabolic acidosis is common in HD patients, since dialytic repletion of the bicarbonate stores is often far from complete; acidosis seems to be less common in CAPD patients, who are continuously provided with lactate from the dialysis fluid as a buffer source. Experimental and clinical studies have shown that metabolic acidosis induces negative nitrogen balance, increased muscle protein degradation and increased oxidation of the branched-chain amino acids (valine, leucine, isoleucine). Acidosis is the only uremic toxic factor identified which stimulates protein catabolism. Correction of metabolic acidosis in HD patients normalizes low muscle intracellular concentrations of the branched-chain amino acids and reduces signs of renal osteodystrophy. The long-term influence of correction of acidosis on nutritional status, morbidity and mortality needs to be assessed in prospective studies.