Division of Nephrology, Department of Medicine and 1 Department of Food and Nutrition, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Abstract |
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Methods. Three groups were identified based on three consecutive monthly predialysis plasma bicarbonate concentrations (PHCO3) and pH values. The effect of correction of metabolic acidosis on nutritional parameters was also studied in acidotic patients.
Results. The mean PHCO3 ranged from 19.2± 0.4 mmol/l in group A (n=21) to 24.4±0.3 mmol/l in group B (n=80) and 27.5±0.4 mmol/l in group C (n=19). The adequency of dialysis (Kt/V) and ultrafiltration rates was comparable in the three groups. When compared with group B, group A had significantly higher body mass index (BMI), triceps skin fold thickness (TSF), dietary protein intake (DPI), normalized protein catabolic rate (nPCR) as well as serum creatinine, K+ and intact parathyroid hormone (I-PTH). In contrast, when compared with group B, group C had a significantly lower DPI, nPCR, plasma creatinine and albumin. There was no significant difference in plasma inflammatory markers such as C-reactive protein (CRP) and interleukin 6 (IL-6) among all three groups. There was a significant negative correlation between PHCO3 and nPCR (P<0.001), DPI (P<0.001), creatinine (P<0.001). Over a period of 6 months, the correction of metabolic acidosis in the HD patients did not affect nutritional parameters.
Conclusion. These findings suggest that metabolic acidosis as a result of a higher protein intake does not detrimentally affect nutritional status.
Keywords: acidbase balance; haemodialysis; metabolic acidosis; nutrition
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Introduction |
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The basis for metabolic acidosis in patients undergoing HD can be multifactorial. If one considered two examples, the effects on nutrition might be dramatically different. First, if its cause was a higher intake of protein, metabolic acidosis may be associated with better nutrition. Secondly, if the basis of metabolic acidosis was less than ideal HD, metabolic acidosis might be associated with poor nutritional indices. Accordingly, we tried to evaluate both the basis of the metabolic acidosis and the nutritional state in a population of HD patients in a cross-sectional analysis. We also performed a prospective study where patients with metabolic acidosis were dialysed against a higher alkali load to determine if this led to an improvement in their nutritional indices.
Results reported here indicate that HD patients with metabolic acidosis have a higher protein intake and thus a higher normalized protein catabolic rate (nPCR), and are associated with better nutritional parameters. The correction of metabolic acidosis in the acidotic HD patients did not affect nutritional parameters.
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Subjects and methods |
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The HD patients were divided into three groups based on three consecutive monthly predialysis acidbase analyses. Group A had a predialysis PHCO3 that was consistently 21 mmol/l and pH <7.38; group B had a predialysis PHCO3 that was consistently between 21 and 26 mmol/l and pH 7.387.42; and group C had a predialysis PHCO3 that was consistently >26 mmol/l and pH >7.42. The mean values of the three measurements were used to present the acidbase status. Correction of metabolic acidosis by adjusting the
concentration of the dialysate was performed for 6 months in group A. During the first month of the study, the dialysate
concentration was increased from 35 to 38 mmol/l. During the rest of the study period, the dialysate was adjusted to 3840 mmol/l in order to achieve a predialysis PHCO3 of 2326 mmol/l.
To evaluate the role of metabolic acidosis on nutritional status, blood was drawn from the arterial side of the arterio-venous (AV) fistula at the start of the dialysis on the midweek day to avoid different predialysis PHCO3 on different weekdays. During blood sampling the patient was at rest and there was no hand motion. Arterial blood gas was measured from a whole blood sample taken anaerobically. The samples were analysed by ABL 510 (Radiometer, Copenhagen, Denmark) within 30 min to avoid a decrease in PHCO3 due to the delayed measurement.
Methods
The following nutritional parameters were evaluated: anthropometry, nPCR, dietary protein intake (DPI) and biochemical markers.
Anthropometry
Anthropometric measurements were performed after HD, using standard techniques, and included: height, weight, body mass index (BMI); weight divided by height squared, triceps skinfold thickness (TSF) as an index of body fat, and mid-arm circumference (MAC) and midarm muscle circumference (MAMC) as an index of muscle mass. The non-dominant arm was chosen for these measurements, unless that arm contained a vascular access site, in which case the other arm was used. TSF was measured with a skinfold caliper (Clifton, NJ, USA) and MAC with a metal tape measure. MAMC was calculated according to the formula: MAMC=MAC-(0.314xTSF).
nPCR and DPI
nPCR, which gives an approximation of the protein intake at a steady state, was calculated according to the standard equations [4]. Kt/V (K, urea clearance; t, dialysis time; V, distribution volume of urea), an index of dialysis adequacy, was determined using the percentage reduction of urea. DPI was obtained from a 3-day diet recall.
Biochemical markers
Biochemical markers were measured by standard laboratory techniques with an automatic analyser (AU 5000 chemistry analyser; Olympus, Tokyo, Japan). Plasma intact parathyroid hormone (I-PTH) concentration was measured by radioimmunoassay using intact-Parathyoid Hormone Immunoassay Kit (Nichols Institute Diagnosis, San Juan Capistrano, CA, USA). Plasma CRP concentration was determined by the rate nephelometry (Beckman Instruments, Inc., Galway, Ireland). Plasma IL-6 concentration was measured by ELISA (R&D Systems Inc. Minneapolis, MN, USA).
Statistics
All results are expressed as mean±standard error of the mean (SEM). The difference among groups was analysed by a one-way analysis of variance (ANOVA) followed by Scheffé's test for multiple comparisons. Pearson's correlation coefficient was used to determine the relationship between the PHCO3 and nutritional parameters. A within-group comparison among post-treatment values and baselines was analysed by repeated measures ANOVA. A P value of <0.05 was considered statistically significant.
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Results |
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Protein intake and protein catabolism
There was a significant and inverse correlation between the nPCR and the PHCO3 at the beginning of the dialysis period. Interestingly, these values matched the trend in DPI.
Biochemical markers
As a general trend, there again appeared to be an inverse relationship between the PHCO3 and the parameters in plasma related to clearance by dialysis, including creatinine, urea, K+ and phosphate (Table 2). A similar trend was evident in the parameters related to protein and lipid level (albumin, total protein, cholesterol and transferrin levels) as well as with I-PTH levels. In contrast, there was no obvious trend evident with the inflammatory markers, CRP and IL-6.
When all of the above were analysed statistically, there was no significant correlation between predialysis PHCO3 and body weight, sex, Kt/V and UFR. A weakly positive correlation was evident between the PHCO3 and age (r=0.27, P<0.05). There was no significant correlation between predialysis PHCO3 and anthropometry. In contrast, there was a significant negative correlation between PHCO3 and DPI (r=0.60, P<0.001), and nPCR (r=0.50, P<0.001) (Figure 1); nPCR was positively correlated with DPI (r=0.71, P<0.001) (Figure 2
). Although there was a significant inverse correlation between PHCO3 and urea (r=0.31, P<0.05) and Cr (r=0.45, P<0.001), there was no significant correlation between predialysis PHCO3 and albumin concentration in HD patients (r=0.21, P=not significant). Although diabetes mellitus and age had an association with predialysis PHCO3 and abnormal nutritional parameters, they were not found to be major confounders that affect the association between PHCO3 and other variables (listed above) after controlling both of them.
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Effect of correction of metabolic acidosis on nutritional parameters
The data for this portion of the study are provided in Table 3. Four patients did not complete the study because two were hospitalized due to gastrointestinal bleeding and myocardial infarction, and the other two were intolerant to high dialysate
concentration. In total, 17 HD patients with metabolic acidosis completed the second study. As expected, the PHCO3 (18.4±0.3 to 24.2±0.2 mmol/l, P<0.001) and the arterial pH (7.34±0.01 to 7.41±0.01, P<0.001) increased over the 6 months of treatment. There was no significant change in interdialysis body weight gain, MAP, haemoglobin and Kt/V. There was a significant decrease in plasma I-PTH (326±61 vs 246±49 ng/l, P<0.05) and K+ (5.2±0.2 vs 5.0±0.1 mmol/l, P<0.05) after the correction of metabolic acidosis. However, nutritional parameters were not significantly affected.
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Discussion |
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It did not appear that intradialytic factors contributed to the presence of metabolic acidosis because our patients were dialysed with the same dialysate concentration and they were nearly aneuric. In addition, patients with metabolic acidosis had similar Kt/V values and UFRs as those with normal acidbase and metabolic alkalosis, suggesting that dialysis adequacy and interdialysis extracellular fluid (ECF) volume gain were not responsible for different values of predialysis PHCO3. Therefore, it appears that a higher rate of endogenous acid production from protein oxidation was responsible for the lower predialysis PHCO3. Indeed, the nPCR was higher in the acidotic group. The next step was to evaluate the source of protein. Both exogenous and endogenous protein catabolism could contribute to the protein catabolic rate. Our data suggested that a higher protein intake was the main factor contributing to higher nPCR and an increased daily acid production, because the higher nPCR is associated with a higher daily protein intake and metabolic acidosis. Similarly, a lower protein intake and nPCR could have contributed to metabolic alkalosis in HD patients.
While protein intake could have been responsible for the lower PHCO3, we evaluated factors that would augment protein catabolism, acidosis and inflammation. Although inflammation also decreases appetite and protein intake, acidosis per se does not have major effect on protein intake [6]. Serum CRP concentration and IL-6 reflect the activity of cytokine-mediated acute phase processes and has been used as a marker of inflammation in HD patients [7]. Notwithstanding, CRP and cytokine IL-6 levels were comparable in three groups, suggesting that inflammation was not a causative factor for a higher nPCR in our patients. Because metabolic acidosis is a major factor influencing protein catabolism and contributing to a higher nPCR, their protein intake should be expected to be normal or lower.
HD patients with metabolic acidosis had a significantly higher serum creatinine concentration. There was also a significant negative correlation between the PHCO3 and plasma creatinine level; the latter is considered to reflect somatic protein (muscle mass). Predialysis serum creatinine concentration can also reflect protein intake and endogenous acid production because creatinine also comes from the ingested meat and meat proteins are an important source of sulfur-containing amino acids [8]. This may explain in part why patients with a higher serum creatinine concentration had a higher somatic protein mass and a higher protein intake in well dialysed acidotic HD patients [9].
Serum albumin tended to be higher in acidotic HD patients compared with HD patients with normal acidbase parameters. Hypoalbuminaemia in HD patients is primarily a consequence of reduced albumin synthesis rather than increased albumin catabolic rate [10]. The cause of decreased albumin synthesis is primarily a response to inflammation, acidosis and protein malnutrition [10]. Comparable serum CRP and IL-6 concentration in three groups suggested that inflammatory status is not the major factor responsible for the differences in serum albumin concentration. It is known that higher protein intake augments albumin synthesis, whereas chronic moderate metabolic acidosis has been shown to decrease albumin synthesis [11]. Therefore a higher protein intake might increase albumin synthesis and this could outweigh the reduction in albumin synthesis due to metabolic acidosis.
In this study, HD patients with metabolic acidosis had a higher BMI and fat mass. This finding may be related to their higher protein and caloric intake. BMI, a standard measure of non-skeletal mass, has been used as a marker of energy nutritional status (energy store). It has recently been reported that HD patients with low BMI had a clinically significant increased risk of mortality [12]. The effect of a high BMI on mortality risk in HD patients is found to be opposite to that reported for healthy adults. The fact that greater energy reserves in HD patients might offer a protective effect for caloric malnutrition supports the idea that the effect of a higher BMI is to reduce mortality risk. Whether acidotic HD patients with a higher BMI have a reduced risk of mortality deserves further study.
The role of correction of metabolic acidosis on nutritional parameters in dialysis patients is still uncertain. Correction of metabolic acidosis in HD patients improves protein catabolism and increased plasma branched-chain amino acid, although there is a lack of increase in body mass assessed by anthropometry and whole body K+ measurement [3,13]. Only one study in continuous ambulatory peritoneal dialysis (CAPD) patients reported that the increase in body weight and mid-arm circumference was greater in the group with fully corrected acidosis [14]. Contrary to these reports, the correction of metabolic acidosis for 6 months in this study did not induce any significant changes in nutritional parameters, further suggesting that mild to moderate metabolic acidosis does not deleteriously affect nutritional status in well dialysed HD patients. These findings are consistent with the previous study that has shown that the correction of metabolic acidosis does not increase serum albumin levels, protein catabolic rates or dietary protein intake in HD patients [6,15].
It has been observed that the relative risk of death per group of patients with different PHCO3 from 12000 HD patients in a retrospective study was increased dramatically, only for values <15 mmol/l. The degree of metabolic acidosis in acidotic patients in this study was mild to moderate, with the PHCO3 values ranging from 15.9 to 20.8 mmol/l. Metabolic acidosis may adversely influence calcium, phosphate, vitamin D and PTH metabolism. Although PTH values were higher in acidotic HD patients and modestly reduced by acid correction, the overall non-nutritional and nutritional benefit of acid correction must be weighed against the associated side effects such as increased thirst, fluid overloading, hypertension, calcium phosphate precipitation and vasoconstriction.
In conclusion, our objective was to distinguish between metabolic acidosis as a cause of poor nutrition as compared with better nutrient intake leading to metabolic acidosis due to greater hydrogen production. From this study, HD patients with metabolic acidosis had a higher protein intake and thus a higher nPCR, and were associated with better nutritional parameters. We could not confirm that metabolic acidosis was a negative factor in chronic HD patients because it could reflect a higher protein intake, the precusor of hydrogen production.
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Acknowledgments |
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Notes |
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References |
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