| Abstract|| |
One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD) is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V ≥ 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3‾ ), Kt/V, normalized protein catabolic rate (nPCR) and body mass index (BMI) in these patients. The mean age of the study patients was 55 ± 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 ± 0.16, pH was 7.40 ± 0.15, serum HCO 3‾ was 23.18 ± 2.38 mEq/L, serum albumin was 4.03 ± 0.56 g/dL, nPCR was 1.00 ± 0.16 g/kg/day, post-dialysis body weight was 58.50 ± 11.50 kg and BMI was 23.47 ± 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004), and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019). On multiple regression analysis, the predictors of serum albumin were serum HCO3‾ and BMI (direct effect) and nPCR (inverse effect). In 17 patients on MHD with serum HCO3‾ <22 mEq/L, there was a significant inverse correlation between HCO 3 and nPCR (r = 0.492, P = 0.045), and these patients had significantly lower serum albumin compared with patients with serum HCO3‾ >22 mEq/L (P = 0.046). These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD.
|How to cite this article:|
Soleymanian T, Ghods A. The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients. Saudi J Kidney Dis Transpl 2011;22:1149-54
|How to cite this URL:|
Soleymanian T, Ghods A. The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Dec 5];22:1149-54. Available from: http://www.sjkdt.org/text.asp?2011/22/6/1149/87219
| Introduction|| |
Malnutrition occurs in a large number of patients on maintenance hemodialysis (MHD) and is associated with increased morbidity and mortality. , Low serum albumin is a strong predictor of death in dialysis patients.  Many renal failure patients have progressive wasting and malnutrition despite apparently adequate dialysis,  and there is progressive decline of lean body mass in patients with end-stage renal disease (ESRD),  indicating on-going catabolism of muscle proteins. Studies have indicated that one of the major causes of malnutrition in these patients is systemic acidosis. ,,,,, Metabolic acidosis, by causing both malnutrition ,, and inflammation, , may play a major role in increased mortality of chronic kidney disease (CKD) patients. The aim of this study was to evaluate the role of low serum bicarbonate on serum albumin concentration and normalized protein catabolic rate (nPCR) in a group of well-dialyzed MHD patients.
| Subjects and Methods|| |
One-hundred and sixty-five of the in-center HD patients on regular MHD at the Division of Nephrology, Hashemi Nejad Hospital, Tehran, Iran, were studied. Forty-seven of these anuric patients, including 25 males and 22 females, were included in the study. All study patients had two consecutive mean Kt/V ≥1, no cachexia [body mass index (BMI) <19], neoplasia, systemic disease or recent acute illnesses. All the patients were dialyzed by acetate HD thrice weekly, each session lasting at least 240 minutes, and with appropriate polysulfone membrane, blood flow rate and dialysate flow rate. The underlying renal disease was diabetes in six patients, autosomal-dominant polycystic kidney disease in five patients and chronic hypertension and unknown nephropathy in 32 patients.
Samples for blood urea nitrogen (BUN) were drawn from the arterial side of the arteriovenous fistula at the beginning and end of a dialysis session and at the start of the next dialysis session. The duration of each dialysis session, duration of time between dialysis sessions and inter-dialysis weight gain were recorded. Blood for laboratory data were drawn from the arterial side of the AV fistula at the start of the dialysis session.
In order to evaluate the role of different parameters on patients' serum albumin concentration, as expression of nutritional status, arterial pH, serum bicarbonate (HCO3 - ), serum albumin (Alb), KT/V, nPCR and BMI were measured. All data are expressed as mean ± SD. Pearson correlation, linear regression analysis and student's t test were used for statistical evaluation.
| Results|| |
The mean age of the study patients was 55 ± 13.8 years. Other data are mentioned in [Table 1]. There was significant direct correlation between serum albumin and BMI (P = 0.004, r = 0.415) [Figure 1] and significant direct correlation between serum albumin and serum bicarbonate (P = 0.019, r: 0 = 341) [Figure 2]. There was no significant correlation between serum albumin and KT/V, age or sex.
|Figure 1: Correlation between serum albumin concentration and body mass index.|
Click here to view
|Figure 2: Correlation between serum albumin concentration and serum bicarbonate levels.|
Click here to view
|Table 1: Descriptive statistics of 47 patients on maintenance hemodialysis.|
Click here to view
Multiple regression analysis of the data [Table 2] indicated that the predictors of serum albumin concentration are serum bicarbonate concentration and BMI (direct effect) and nPCR (inverse effect).
In patients (17 cases) with serum HCO3 - ≤22 mEq/L, there was a significant inverse correlation between serum HCO3 - and nPCR (P = 0.045, r = 0.492) [Figure 3]. Patients with serum HCO3 - concentration ≤22 mEq/L showed significantly lower serum albumin concentration compared with patients with serum HCO3 - >22 mEq/L (P = 0 0.046).
|Figure 3: Correlation between serum bicarbonate levels and normalized protein catabolic rate.|
Click here to view
| Discussion|| |
There is on-going catabolism of muscle proteins in dialysis patients.  Continuing catabolism in the presence of adequate dialysis  implies that some other factors contribute to the malnutrition of patients on HD. Low serum albumin concentration is one of the most sensitive indices of malnutrition in HD patients, , and evidence indicates that metabolic acidosis contributes to the low level of serum albumin in dialysis patients. ,,,, Also, there is an association between low serum albumin, as expression of malnutrition, and mortality in HD patients. ,,
Several mechanisms contribute to this. They include increased protein catabolism , through augmentation of the transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway,  and also directly stimulating oxidative catabolism through activation of branched-chain α-keto acid dehydrogenase; decreased protein synthesis; insulin resistance; decrease in serum leptin level; and inflammation. ,,,,, Moreover, several studies have shown that correction of metabolic acidosis causes an improvement in nutritional status in HD patients. ,,
The effect of metabolic acidosis on nutritional status and survival of HD patients is a controversial issue. While some studies have shown that mild to moderate metabolic acidosis in HD patients indicates a higher protein intake and better nutritional status and survival, ,,,,,,, others believe that metabolic acidosis in CKD and dialysis patients, through catabolism of endogenous protein and inflammation, induce protein-energy malnutrition and poor outcome.7, 8, 20, 32, 34, 44
In a recent study of 56,385 maintenance HD patients across the United States by Wu et al,  the authors reported that after adjusting for case-mix and nine markers of malnutrition inflammation complex syndrome (MICS), patients with HCO3 - values >22 mEq/L had a lower death risk.
In this study, we analyzed the effects of different parameters on serum albumin concentration. Patients with adequate dialysis prescription were enrolled; therefore, dose of dialysis had no effect on serum albumin concentration. Significant direct correlation between serum albumin concentration and BMI indicated that serum albumin is a perfect marker of nutritional status of MHD patients. According to multiple regression analysis of data, serum HCO3 - concentration and BMI showed positive effect on serum albumin concentration, and nPCR had a negative effect. As the variations in nPCR and serum albumin concentration are in the opposite direction, it seems extremely unlikely that a change in the dietary intake could be an explanation for the observed changes. The direct effect of serum HCO3 - and inverse effect of nPCR on serum albumin is consistent with the concept that acidosis in HD patients with adequate dialysis prescription probably is a result of catabolism and breakdown of the endogenous proteins, leading to high nPCR in these patients.
In conclusion, we found that patients on MHD with metabolic acidosis had lower serum albumin concentration despite adequate dialysis treatment. There was an inverse effect of nPCR on serum albumin concentration in acidotic MHD patients, indicating that metabolic acidosis, probably by augmenting catabolism of endogenous protein, exerts a deleterious effect on nutritional status of MHD patients.
| References|| |
|1.||Kopple JD. Protein-energy malnutrition in maintenance dialysis patients. . Am J Clin Nutr 1997;65:1544-57. |
|2.||Kopple JD. Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients. ASAIO J 1997;43:246-50. |
|3.||Spiegel DM, Breyer JA. Serum albumin: a predictor of long-term outcome in peritoneal dialysis patients. Am J Kidney Dis 1994;23: 283-5. |
|4.||Kopple JD, Swendseid ME. Protein and amino acid metabolism in uremic patients undergoing maintenance hemodialysis. Kidney Int 1975;7 (suppl 2):564-72. |
|5.||Coles GA. Body composition in chronic renal failure. Q J Med 1972;41:25-47. |
|6.||Mitch WE. Influence of metabolic acidosis on nutrition. Am J Kidney Dis 199729:46-8. |
|7.||Bergstrom J. Metabolic acidosis and nutrition in dialysis patients. Blood Purif 1995;13:361-7. |
|8.||Movilli E, Bossini N, Viola BF, et al. Evidence for an independent role of metabolic acidosis on nutritional status in hemodialysis patients. Nephrol Dial Transplant 1998;13:614-78. |
|9.||Mitch WE. Metabolic acidosis stimulates protein metabolism in uremia. Miner Electrolyte Metab 1996;22:62-5. |
|10.||Ballmer PE, McNurlan MA, Hulter HN, Anderson SE, Garlick PJ, Krapf R. Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. J Clin Invest 1995;95:39-45. |
|11.||Movilli E, Zani R, Carli O, et al. Correction of metabolic acidosis increases serum albumin concentration and decreases kinetically evaluated protein intake in hemodialysis patients: a prospective study. Nephrol Dial Transplant 1998;13:1719-22. |
|12.||Ballmer PE, McNurlan MA, Hulter HN, Anderson SE, Garlick PJ, Krapf R. Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. J Clin Invest 1995;95:39-45. |
|13.||Reaich D, Channon SM, Scrimgeour CM, Goodship TH. Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans. Am J Physiol 1992;263:E735-9. |
|14.||Papadoyannakis NJ, Stefanidis CJ, McGeown M. The effect of the correction of metabolic acidosis on nitrogen and potassium balance of patients with chronic renal failure. Am J Clin Nutr 1984;40:623-7. |
|15.||Lin SH, Lin YF, Chin HM, Wu CC. Must metabolic acidosis be associated with malnutrition in haemodialysed patients? Nephrol Dial Transplant 2002;17:2006-10. |
|16.||Pickering WP, Price SR, Bircher G, Marinovic AC, Mitch WE, Walls J. Nutrition in CAPD: Serum bicarbonate and the ubiquitin-proteasome system in muscle. Kidney Int 2002;61: 1286-92. |
|17.||Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease. J Am Soc Nephrol 1996;7:728-36. |
|18.||Movilli E, Mombelloni S, Gaggiotti M, Maiorca R. Effect of age on protein catabolic rate, morbidity, and mortality in uremic patients with adequate dialysis. Nephrol Dial Transplant 1993;8:735-9. |
|19.||Bailey JL, Wang X, England BK, Price SR, Ding X, Mitch WE. The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway. J Clin Invest 1996; 97:1447-53. |
|20.||Mitch WE. Uremic acidosis and protein metabolism. Curr Opin Nephrol Hypertens 1995;4: 488-92. |
|21.||Owen SR, Lew NL, Yan Liu SM, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentrations as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 1993;329:1001-6. |
|22.||Acchiardo SR, Moore LW, La Tour PA. Malnutrition as the main factor in the morbidity and mortality of hemodialysis patients. Kidney Int 1983;524:S199-203. |
|23.||Kalantar-Zadeh K, Fouque D, Kopple JD. Outcome research, nutrition, and reverse epidemiology in maintenance dialysis patients. J Ren Nutr 2004;14:64-71. |
|24.||Williams B, Hattersley J, Layward E, Walls J. Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia. Kidney Int 1991;40:779-86. |
|25.||Mitch WE. Cellular mechanisms of catabolism activated by metabolic acidosis. Blood Purif 1995;13:368-74. |
|26.||Bailey JL, Wang X, England BK, Russ Price S, Ding X, Mitch WE. The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of the ATP-dependent ubiquitin-proteasome pathway. J Clin Invest 1996;97:1447-53. |
|27.||May RC, Hara Y, Kelly RA, Block KP, Buse MG. Branched-branched amino acid metabolism in rat muscle: Abnormal regulation in acidosis. Am J Physiol 1987;252:E712-8. |
|28.||Franch HA, Mitch WE. Catabolism in uremia: The impact of metabolic acidosis. J Am Soc Nephrol 1998;9:S78-81. |
|29.||Bailey JL, Mitch WE. Twice-told tales of metabolic acidosis, glucocorticoids, and protein wasting: What do results from rats tell us about patients with kidney disease? Semin Dial 2000; 13:227-31. |
|30.||Kalantar-Zadeh K, Mehrotra R, Fouque D, Kopple JD. Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure. Semin Dial 2004;17:445-65. |
|31.||Mehrotra R, Kopple JD, Wolfson M. Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Kidney Int Suppl 2003;64:S13-26. |
|32.||Mitch WE. Insights into the abnormalities of chronic renal disease attributed to malnutrition. J Am Soc Nephrol 2002;13(Suppl 1):S22-7. |
|33.||Hara Y, May RC, Kelly RA, Mitch WE. Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats. Kidney Int 1987;32:808-14. |
|34.||Graham KA, Reaich D, Channon SM, Downie S, Goodship TH. Correction of acidosis in hemodialysis decreases whole body protein degradation. J Am Soc Nephrol 1997;8:632-7. |
|35.||Williams AJ, Dittmer ID, McArley A, Clarke J. High bicarbonate dialysate in haemodialysis patients: effects on acidosis and nutritional status. Nephrol Dial Transplant 1997;12:2633-7. |
|36.||Movilli E, Zani R, Carli O, et al. Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: A prospective study. Nephrol Dial Transplant 1998;13:1719-22. |
|37.||Lowrie EG, Lew NL. Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990;15:458-82. |
|38.||Bommer J, Locatelli F, Satayathum S, et al. Association of predialysis serum bicarbonate levels with risk of mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2004;44: 661-71. |
|39.||Uribarri J. Moderate metabolic acidosis and its effects on nutritional parameters in hemodialysis patients. Clin Nephrol 1997;48:238-40. |
|40.||Dumler F, Falla P, Butler R, Wagner C, Francisco K. Impact of dialysis modality and acidosis on nutritional status. ASAIO J 1999;45: 413-7. |
|41.||Gao H, Lew SQ, Bosch JP. Moderate metabolic acidosis and its effects on serum parameters in hemodialysis patients. Nephron 2000;86:135-8. |
|42.||Leavey SF, Strawderman RL, Young EW, et al. Cross-sectional and longitudinal predictors of serum albumin in hemodialysis patients. Kidney Int 000;58:2119-28. |
|43.||Chauveau P, Fouque D, Combe C, et al. Aciosis and nutritional status in hemodialyzed patients. French Study Group for Nutrition in Dialysis. Semin Dial 2000;13:241-6. |
|44.||Jenkins D, Burton PR, Bennett SE, Baker F, Walls J. The metabolic consequences of the correction of acidosis in uremia. Nephrol Dial Transplant 1989;4:92-5. |
|45.||Wu DY, Shinaberger CS, Regidor DL, McAllister CJ, Kopple JD, Kalantar-Zadeh K.. Association between serum bicarbonate and death in hemodialysis patients: Is it better to be acidotic or alkalotic? Clin J Am Soc Nephrol 2006;1:70-8. |
Division of Nephrology, Shariati Hospital, Tehran University of Medical Sciences, Tehran
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]