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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2012  |  Volume : 23  |  Issue : 6  |  Page : 1202-1207
Branched chain amino acid profile in early chronic kidney disease

1 Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, A.P., India
2 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, A.P., India

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Date of Web Publication17-Nov-2012


The nutritional status in chronic kidney disease (CKD) patients is a predictor of prognosis during the first period of dialysis. Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid profile. Of these, the plasma levels of branched chain amino acids (BCAA), especially valine and leucine, correlate well with nutritional status. Plasma BCAAs were evaluated along with albumin and C-reactive protein in 15 patients of early stages of CKD and 15 age- and sex-matched healthy controls. A significant decrease in plasma valine, leucine and albumin levels was observed in CKD patients when compared with the controls (P <0.05). No significant difference in C-reactive protein (CRP) levels was observed between the two groups. Malnutrition seen in our CKD patients in the form of hypoalbuminemia and decreased concentrations of BCAA points to the need to evaluate the nutritional status in the early stages itself. Simple measures in the form of amino acid supplementation should be instituted early to decrease the morbidity and mortality before start of dialysis in these patients.

How to cite this article:
Kumar M A, Bitla AR, Raju K, Manohar SM, Kumar V S, Narasimha SP. Branched chain amino acid profile in early chronic kidney disease. Saudi J Kidney Dis Transpl 2012;23:1202-7

How to cite this URL:
Kumar M A, Bitla AR, Raju K, Manohar SM, Kumar V S, Narasimha SP. Branched chain amino acid profile in early chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Oct 7];23:1202-7. Available from: https://www.sjkdt.org/text.asp?2012/23/6/1202/103560

   Introduction Top

Nutritional and metabolic derangements, often termed as uremic malnutrition, are highly prevalent among patients with chronic kidney disease (CKD), and significantly affect the high morbidity and mortality rate observed in this patient population. Much has been studied and reported about malnutrition in advanced stages of CKD. However, there is paucity of data concerning the nutritional status in the early stages of CKD. [1],[2],[3]

Hence, efforts directed toward a better understanding of these conditions are required to effectively treat them, thereby improving the quality of life of CKD patients. Interventions to improve the nutritional status and metabolic status of uremic patients have been shown to improve the expected outcome in CKD patients. [4] The nutritional status in pre-dialysis patients is a predictor for their prognoses in the first period of dialysis. Hence, assessment of nutritional status of CKD patients is important.

In CKD patients, simple biochemical measures reflecting the visceral protein stores, such as serum albumin, serum creatinine and blood urea nitrogen (BUN), as well as less commonly used parameters such as prealbumin and insulin-like growth factor-1, reflect the nutritional status. [5] Serum albumin is the most commonly used nutritional marker. Low levels of serum albumin are highly predictive of poor clinical outcomes in all stages of CKD. [4],[6],[7]

Altered plasma and muscle amino acid profile have also been proposed as nutritional markers. CKD patients have well-defined abnormalities in their plasma and, to a lesser extent, in their muscle amino acid profiles. Commonly, essential amino acid concentrations are low and non-essential amino acid concentrations are high. [8] The etiology of this abnormal profile is multifactorial. Inadequate dietary intake is a major contributing factor; however, certain abnormalities occur even in the presence of adequate dietary nutrient intake, indicating that the uremic milieu has an additional effect. [9] In addition, inflammation commonly seen in CKD patients has been shown to cause low plasma amino acid concentrations in CKD patients. [10]

Among the amino acids, the plasma levels of branched chain amino acids (BCAAs) valine, leucine and isoleucine have been the focus, primarily due to their importance in skeletal muscle energy metabolism, and leucine has been shown to enhance protein synthesis in vitro. [11] It is even possible to modify appetite in uremic patients by administering BCAA.

To the best of our knowledge, there are no reports on nutritional status in early stages of CKD from India. Nutrition of Indians differs from that of western counterparts. The requirement of BCAA in Indians has been shown to be higher than that proposed by FAO/WHO/ UNU. [12] This study was thus taken up to evaluate the biochemical markers of nutrition, especially the BCAA profile, in early stages of CKD patients and to study its association with inflammation, as the association of malnutrition and inflammation are important components of the malnutrition, inflammation and atherosclerosis (MIA) syndrome associated with increased mortality. [13]

   Materials and Methods Top

In the present study, 15 patients with CKD stages I and II classified as per the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF K/DOQI) guidelines [14] attending the Nephrology Outpatient Department at Sri Venkateswara Institute of Medical Sciences, Tirupati (A. P.), India, were included after informed consent. Patients with acute renal failure and acute on chronic renal failure were excluded from the study. Fifteen age- and sex-matched healthy individuals from among the patient's relatives and hospital staff was taken as controls. The causes of CKD were type 2 diabetes (n = 5), hypertension (n = 7), Lupus nephritis (n = 1), membranous nephro-pathy (n = 1) and chronic pyelonephritis (n = 1). The baseline characteristics of the patients are given in [Table 1].
Table 1: Baseline characteristics of the study group patients.

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Five milliliters of heparinized venous blood samples was collected from the patients and healthy subjects in the morning, after an overnight fast. The samples were centrifuged at 2000 rpm for 15 min, and the plasma separated and stored in vials at -80°C until analysis. The samples were processed for BCAAs, urea, creatinine, albumin and C-reactive protein (CRP). Plasma urea, creatinine, albumin and CRP were quantitatively measured on a Beckman Synchron CX9 fully automated analyzer using commercial kits. Plasma BCAAs were estimated by using reverse phase high performance liquid chromatography (RP-HPLC) using pre-column derivatization with O-phthaladehyde-Mercaptoethanol. [15]

   Statistical Analysis Top

All values obtained were expressed as mean ± standard error of mean (SEM). Mann Whitney U test was performed to compare the difference in the means between the controls and the study group. A P-value <0.05 was considered as statistically significant. Spearman's rank correlation analysis was done to study the correlation between albumin and amino acids, albumin and CRP as well as CRP and amino acids. Statistical analysis was performed using SPSS for Windows Version 11.5.

   Results Top

As shown in [Table 2], a significant decrease in plasma concentration of amino acids valine, leucine and albumin were observed in patients with CKD (study group) when compared with controls (P <0.005). No significant difference was observed in CRP levels between the two groups (P = 0.425). [Figure 1]a and b show the distinctly lower concentration of valine and leucine, respectively, in CKD patients compared with controls. Isoleucine levels were found to be similar in the study and control groups [Figure 1]c. No significant correlation was observed between albumin and valine, leucine and isoleucine in the CKD patients (study group) [Table 3]. CRP showed a negative correlation with albumin, which was statistically insignificant. Among the BCAAs, only valine showed a significant negative correlation with CRP (r = -0.679, P = 0.022).
Figure 1: Scatter plots for branched chain amino acids in study group and control group.

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Table 2: Showing mean, standard error mean (SEM) and P-value for biochemical parameters among chronic kidney disease patients (study group) and control.

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Table 3: Correlation analysis between inflammatory and nutritional markers.

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   Discussion Top

A significant decrease in the plasma concentration of valine and leucine was observed in CKD patients when compared with the control group (P <0.05). This is in agreement with previous reports. [16],[17],[18] The decrease in plasma isoleucine concentration was not found to be statistically significant. This is in line with the reports of Suliman et al [10] , who observed a statistically significant decrease in valine and leucine, while no change in isoleucine concentrations were observed in CKD patients when compared with controls. Moderate decrease in BCAAs has been reported only in the advanced stage of renal failure, which is more of nutritional in origin. [16]

Plasma levels of BCAAs have been shown to predict nutritional status in patients on hemodialysis. As per one report, valine in plasma best predicted the nutritional status, [19] while another suggested leucine to be as good a predictor as valine. [20] The plasma pool represents only a small fraction of the total body content for a given amino acid. For most amino acids, the intracellular concentration in skeletal muscle (the largest pool of free amino acids immediately available for protein synthesis) is higher than in plasma. [21] In patients with renal failure, the plasma concentrations of several amino acids do not reflect the intracellular concen trations in the muscle cells. [22] Muscle biopsy studies have shown low muscle valine and normal to elevated isoleucine and leucine in untreated uremic patients. [23]

Metabolic acidosis induces protein breakdown via an activation of both cytosolic ATP-ubiquitin-dependent proteolytic pathway and branched chain keto acid dehydrogenase, responsible for an irreversible BCAA breakdown. [24] Correcting metabolic acidosis decreases the elimination of BCAA in patients with renal failure. [25] This is more likely to occur in the later stages of CKD, where metabolic acidosis will develop in these patients.

Abnormal amino acid profile in CKD resembles protein malnutrition to some extent. However, abnormal AA profile has been reported even in CKD with normal nutritional status. [26] Serum albumin was measured as a nutritional marker. A significant decrease in albumin levels were observed in CKD patients compared with the control group (P <0.05). Hypoalbuminemia in advanced CKD patients may reflect non-nutritional factors, such as external losses and decreased synthesis. [6] There is a concern over the appropriateness of serum albumin concentrations to assess nutritional status in CKD patients, especially if confounding factors such as inflammation are not taken into account. Also, the systemic inflammatory response stimulates protein catabolism. [27] Amino acids released from muscle protein provide a substrate for the synthesis of acute phase proteins and proteins of the immune system, [28] which could result in a general reduction in plasma amino acid concentrations. [10] In our study, we evaluated CRP levels as a marker of inflammation. No significant difference was observed in CRP levels between the two groups (P = 0.425). A negative correlation was found between albumin and CRP, although it was statistically insignificant. This indicates that in the early stages of CKD, hypoalbuminemia and decreased concentration of BCAA seen in our patients is due to the malnutrition. Suliman observed that inflammation contributed independently to lower concentrations of plasma BCAA. [10] However, in our study, CRP correlated inversely with all the BCAA, but it showed a significant correlation with only valine (r = -0.679, P = 0.022). Malnutrition affects plasma amino acid concentrations in CKD patients. Hence, the abnormal BCAA profile seen in our patients can be attributed to decreased intake due to anorexia caused by accumulation of uremic toxins.

Pre-dialysis nutritional status of CKD affects their outcome after the initiation of chronic dialysis therapy. [29] Malnutrition seen in our patients belonging to the early stages of CKD, demonstrated by hypoalbuminemia and low plasma concentration of BCAAs, point to the need to evaluate the nutritional status of CKD patients in the early stage itself. Normalization of plasma BCAAs through BCAA supplementation may decrease anorexia and improve energy and protein intake. [30] Hence, early institution of simple measures in the form of amino acid supplementation in the early stages should be undertaken so as to decrease the morbidity and mortality in these patients before start of dialysis.

   References Top

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2.Ikizler TA, Greene J, Wingard RL, Parker RA, Hakim RM. Spontaneous dietary protein intake during progression of chronic renal failure. J Am Soc Nephrol 1995;6:1386-91.  Back to cited text no. 2
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5.Carrero JJ, Qureshi AR, Axelsson J, et al. Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite. Am J Clin Nutr 2007;85:695-701.  Back to cited text no. 5
6.Kaysen GA, Rathore V, Shearer GC. Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int 1995;48:510-6.  Back to cited text no. 6
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13.Stenvinkel P, Heimburger O, Lindholm B, Kaysen GA, Bergström J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000;15: 953-60.  Back to cited text no. 13
14.Available from: http://www.kidney.org/professionals/kdoqi/gui delines_ckd/p4_classg1.html NKF K/DOQI guidelines. [Last accessed on 21.07.2010]  Back to cited text no. 14
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20.Qureshi AR, Alvestrand A, Danielsson A, et al. Factors predicting malnutrition in hemodialysis patients: A cross-sectional study. Kidney Int 1998;53:773-82.  Back to cited text no. 20
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24.Noel JM, Cano, Fouque D, Xavier M. Leverve. Branched-chain Aminoacid: Metabolism, Physiology Function, and Application: Session IV. Am Soc Nutr J 2006;136:299S-307S.  Back to cited text no. 24
25.Mak RH. Effect of metabolic acidosis on branched-chain amino acids in uremia. Pediatr Nephrol 1999;13:319-22.  Back to cited text no. 25
26.Bergström J, Alvestrand A, Furst P. Plasma and muscle free amino acids in maintenance hemodialysis patients without protein malnutrition. Kidney Int 1990;38:108-14.  Back to cited text no. 26
27.Karlstad MD, Sayeed MM. Effect of endotoxic shock on skeletal muscle intracellular electrolytes and amino acid transport. Am J Physiol 1987;252:R674-80.  Back to cited text no. 27
28.Grimble RF. Nutritional modulation of immune function. Proc Nutr Soc 2001;60:389-97.  Back to cited text no. 28
29.Khan IH, Catto GR, Edward N. Death during the first 90 days of dialysis: A case control study. Am J Kidney Dis 1995;25:276-80.  Back to cited text no. 29
30.Bossola M, Tazza L, Luciani G. Mechanisms and treatment of anorexia in end-stage renal disease patients on hemodialysis. J Ren Nutr 2009;19:2-9.  Back to cited text no. 30

Correspondence Address:
Aparna Rajeshwar Rao Bitla
Associate Professor, Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, A. P.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.103560

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  [Table 1], [Table 2], [Table 3]


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