Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 3380 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

ORIGINAL ARTICLE Table of Contents   
Year : 2002  |  Volume : 13  |  Issue : 1  |  Page : 18-23
The Biochemical Status of Vitamin A and Alpha-tocopherol during Different Stages of Renal Disease and its Relationship to Diabetes


Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Click here for correspondence address and email
 

   Abstract 

The status of vitamin A, α-tocopherol and retinol binding protein (RBP) was investigated in 34 type 2 diabetic patients with renal impairment (mean serum creatinine 176 µmol/L), 26 type 2 diabetic patients with chronic renal failure (CRF) (mean serum creatinine 629 µmol/L) and 19 non-diabetic patients with CRF. In renal failure patients, the change in response to the dialysis procedure over the time for all the measured parameters was evaluated. Fasting plasma retinol, α-carotene, β-carotene and α-tocopherol were determined by high-pressure liquid chromatography. The concentrations of RBP in plasma were determined by a double antibody sandwich enzyme linked immunosorbent assay. Concentrations of retinol, RBP and β-carotene were significantly higher in diabetic patients with CRF than in diabetic patients with renal impairment or in non-diabetic patients with CRF. A significant decrease was found for the concentrations of β-carotene (p<0.003) and RBP (p<0.003) in response to the dialysis procedure. Retinol/RBP ratio significantly increased with time (p<0.0004). Serum creatinine concentrations were associated with the increased plasma RBP indicating that RBP may be dependent on renal function and changes in levels of RBP in serum may be used in the assessment of renal function.

Keywords: Diabetes, Nephropathy, Human plasma, Vitamin A, α-tocopherol, Renal failure.

How to cite this article:
Abahusain MA, Al-Nahedh NN. The Biochemical Status of Vitamin A and Alpha-tocopherol during Different Stages of Renal Disease and its Relationship to Diabetes. Saudi J Kidney Dis Transpl 2002;13:18-23

How to cite this URL:
Abahusain MA, Al-Nahedh NN. The Biochemical Status of Vitamin A and Alpha-tocopherol during Different Stages of Renal Disease and its Relationship to Diabetes. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2020 Jan 26];13:18-23. Available from: http://www.sjkdt.org/text.asp?2002/13/1/18/33197

   Introduction Top


Patients with chronic renal failure (CRF) have markedly increased plasma concentrations of retinol and retinol binding protein (RBP),[1],[2],[3] and slightly elevated β-carotene. [4]

The serum RNP of patients on continuous ambulatory peritoneal dialysis (CAPD) declined with the duration on dialysis. [5]

The small molecular size of the free RBP (MW=21,000 Daltons) allows it to cross the glomerular barrier more easily than the RBP bound to pre-albumin (MW=75,000 Daltons). [6],[7] In the normal state, small proteins are filtered through the glomeruli, and taken up and catabolized in the tubular cells. However, The glomerular clearance decreases as the MW increases; the glomerular membrane is nearly impermeable to molecules with MW>60,000 Daltons. [8]

In chronic renal failure, high serum creatinine level is associated with high concentrations of RBP. [1],[9] The RBP and creatinine increase significantly during the acute renal failure, but decrease to baseline after recovery. [10]

The aim of the present study is to answer two questions: Whether the rise in serum retinol, α-tocopherol, α- and β-carotene, and RBP differs in the different stages of the renal disease and whether any differences are due to diabetes.


   Subjects and Methods Top


Sixty diabetic patients (aged 39-78 years) attending King Khalid University Hospital in Riyadh, Saudi Arabia were classified into two subgroups: diabetics with renal impairment (mean serum creatinine 176 µmol/L) (n=34; male/female (M/F) 20/14), diabetics with chronic renal failure (DCRF) (mean serum creatinine 629 µmol/L) (n=26, M/F 3/23). Nineteen Non-diabetic patients with renal failure (NDCRF) (M/F 3/16) were matched in age and sex with the diabetic patients with chronic renal failure. Both groups of patients with CRF were supplemented with multivitamin tablets containing 200 mg vitamin A.

Plasma for the determination of retinol, α-tocopherol, α-carotene, β-carotene and RBP levels was frozen in aliquots and stored at - 70 o C until the time of analysis. Serum creatinine and total urine protein concen­trations were obtained from the patients' files. Blood samples for the diabetic and non-diabetic patients with renal failure were obtained at different times during dialysis (pre-, during and post-dialysis).

The levels of retinol, α-carotene, β-carotene and a-tocopherol were determined by high­ pressure liquid chromatography (HPLC) [11] with some modification. [12] The concentration of RBP in plasma was determined by a double antibody sandwich enzyme linked immunosorbent assay (ELISA). [13]


   Statistical Analysis Top


Two-way analysis of variance (ANOVA) and the t-test were used to evaluate differences between groups. Correlations were computed using Spearman's rank coefficient for non­parametric data. Differences were judged to be significant when P values were less than 0.01. The significance of change in plasma parameter concentrations over time (pre-, during, and post-dialysis) were measured using Wilk's Lambda for the two groups combined and Roy's Max root for the two groups separate. Statistical analyses were done using Mini Tab, version 10, 1996; State College, PA, USA.


   Results Top


[Table - 1] shows the values of the various parameters measured. The mean plasma concentrations of retinol and RBP were significantly higher in both DCRF and NDCRF than in the diabetic patients with renal impairment (P<0.0001, P<0.0001 respectively). The plasma β-carotene level was significantly higher in the DCRF than the NDCRF (P<0.0001) or diabetic patients with renal impairment. The DCRF and NDCRF patients had significantly higher serum creatinine than the diabetic patients with renal impairment (P<0.0001). There was no signi­ficant difference of the serum creatinine and plasma RBP in the two CRF groups [Table - 1].

[Table - 2] shows the mean plasma concen­tration of the studied parameters at pre-, during, and post dialysis for the diabetics and non-diabetic patients with CRF. A significant decrease was found for β-­carotene (P<0.003) and RBP (P<0.003) and a modest decrease was found for α-tocopherol (P<0.02) and α-carotene (P<0.03). Retinol/ RBP ratio significantly increased with time (p<0.0004).

In patients with renal impairment, there was a significant positive correlation between retinol and RBP (r=0.35, p=0.0001), retinol and serum creatinine (r=0.29, p=0.001), retinol and α-tocopherol (r=0.28, p=0.0002), retinol and urine protein (r=0.56, p=0.0001). Serum creatinine was significantly associated with RBP (r=0.4, p=0.0001), and urine protein (r=0.70, p=0.0001). Beta-carotene had a significant positive correlation with a-carotene (r=0.33, p=0.0001). a-carotene correlated positively with a-tocopherol (r=0.28, p=0.004). There was a significant positive correlation between age and retinol (r=0.21, p=0.006), age and RBP (r=0.33, p=0.0001), and age and creatinine (r=0.4, p=0.0001). There was a significant inverse relationship between creatinine clearance and retinol (r=-0.63, p=0.003), creatinine clearance and urine protein (r=-0.55, p=0.01), creatinine clearance and serum creatinine (r=-0.55, p=0.0001) in male patients only, creatinine clearance and age (r=-0.50, p=0.0006) in both males and females.

In CRF patients, all significant correlations were lost with the exception of those of retinol and RBP (p=0.02), serum creatinine and RBP (p=0.02) and serum creatinine and retinol (p=0.04).


   Discussion Top


Retinol, RBP, α-tocopherol and carotenoids status in type 2 diabetic patients with renal impairment, type 2 diabetic patients with CRF and non-diabetic patients with CRF were evaluated.

The plasma β-carotene concentration was significantly higher in the DCRF than the NDCRF or diabetic patients with renal impairment. This rise of β-carotene in the DCRF patients is not due to vitamin A supplementation as both groups of patients with CRF received it. The increased level of β-carotene in the DCRF patients may be related to the disturbed metabolism of lipoproteins due to diabetes. [16]

In this study, the two groups of patients with renal failure whether diabetics or non­-diabetics had markedly increased concen­trations of retinol and RBP when compared to the diabetic patients with renal impairment.

The highly increased levels of retinol and RBP were in agreement with previous reports. [1],[17] In the CRF patients, the plasma retinol and RBP concentrations were on the average three times the normal, similar to the levels reported by others. [1] The retinol level was also elevated among diabetic patients with renal impairment and this is in agreement with previously reported data. [17],[18]

There was a strong correlation between the retinol and RBP levels (p=0.0001). This was consistent with the data of others [1],[17],[19] and to the fact that RBP is the carrier protein for the vitamin. In renal dysfunction, both the excretion and tubular catabolism of RNP are reduced, which result in the accumulation of these proteins in the blood. [8],[20]

The elevated plasma retinol in renal impairment or failure may be due to the increased RBP levels, [1],[19],[21],[22] reduced vitamin excretion and decreased conversion of retinol to retinoic acid. [18]

Patients with CRF have been reported to have high liver retinol content, which suggests an excess of retinol in the whole body. [18] The observed increase of serum retinol in the nephrectomized rats was suggested to be due to the increase in retinol associated with RBP, coupled with the thyroxin binding protein (transthyretin-TTR), besides the upregulation of the hepatic release mechanism in renal disease. [23] It was suggested that renal failure resulted in a change in the signal for release of retinol ­RBP into the circulation. [23]

In our study, there was a positive correlation between serum creatinine and both plasma RBP and retinol, which was consistent with previous reports. [2],[24],[25] Also, there was a significant positive correlation between urine protein and plasma RBP and retinol. Since serum creatinine and urine protein levels usually indicate the renal functional status, this positive correlation indicates that serum retinol and RBP may be dependent on renal function. Accordingly, the changes of the level of RBP in serum and urine may be valuable in assessing the alterations of renal function. It was reported that the serum RBP level was increased with the decrease in glomerular filtration and creatinine clearance. [2] The current study did not confirm these results although there was a significant negative correlation between retinol and creatinine clearance in male diabetic patients.

All the CRF patients in our study, whether diabetic or not, had a decline of the plasma level of all the parameters in response to dialysis; only retinol was not affected. The retinol/RBP ratio significantly increased during dialysis indicating the loss of RBP, probably due to its small size; this was consistent with earlier reports. [4] Others found higher plasma retinol in samples taken immediately post-dialysis in comparison with the pre-dialysis levels. [19]

In conclusion, our study suggests that patients with CRF (diabetic and non­diabetic) had high concentrations of retinol and RBP. Thus, supplementation of vitamin A may not be necessary for these patients. Diabetic patients with CRF had higher plasma β-carotene concentrations than non­diabetic patients with CRF, which may be due to the disturbed metabolism of lipo­proteins in the diabetic state. Moreover, there was correlation between serum creatinine and urine protein concentration, and the plasma RBP indicating the possibility of using it in the assessment of renal function.


   Acknowledgement Top


We would like to express our gratitude and appreciation to the administration of the King Faisal Specialist Hospital and Research Centre, for allowing us to use their excellent facilities. We are grateful to the Biological and Medical Research Department staff (King Faisal Specialist Hospital and Research Center) for their technical assistance in the HPLC analysis. We are also grateful to Dr. Devol, E for his help with data analysis. We express our appreciation to the doctors and nurses at the dialysis unit at King Khalid Hospital for their valuable assistance. We would like to acknowledge the valuable support of the staff at the Research Center, College of Medicine and Clinical Bio­chemistry, College of Medicine.

 
   References Top

1.Smith FR, Goodman DS. The effects of diseases of the liver, thyroid and kidneys on the transport of vitamin A in human plasma. J Clin Invest 1971;50:2426-36.  Back to cited text no. 1    
2.Ayatse JO. Human retinol-binding protein: its relationship to renal function in renal diseases. West Afr J Med 1991;10(3&4): 226-31.  Back to cited text no. 2    
3.Jaconi S, Saurat JH, Siegenthaler G. Analysis of normal and truncated holo- and apo-retinol-binding protein (RBP) in human serum: altered ratios in chronic renal failure. Eur J Endocrinol 1996;134:576-82.  Back to cited text no. 3    
4.Gotloib L, Sklan D, Mines M. Hemo­dialysis. Effect on plasma levels of vitamin A and caroteniods. JAMA 1978;239(8):751.  Back to cited text no. 4    
5.Kabanda A, Jadoul M, Pochet JM, Lauwerys R, van-Ypersele-de-Strihou C, Bernard A. Determinants of the serum concentrations of low molecular weight proteins in patients on maintenance hemodialysis. Kidney Int 1994; 45:1689-96.  Back to cited text no. 5    
6.Kanai M, Raz A, Goodman DS. Retinol­binding protein: the transport protein for vitamin A in human plasma. J Clin Invest 1968;47:2025-44.  Back to cited text no. 6    
7.Raz A, Shiratori T, Goodman DS. Studies on the protein-protein and protein-ligand interactions involved in retinol transport in plasma. J Biol Chem 1970;245(8):1903-12.  Back to cited text no. 7    
8.Strober W, Waldmann TA. The role of the kidney in the metabolism of plasma proteins. Nephron 1974;13:35-66.  Back to cited text no. 8    
9.Goodman DS. Plasma retinol-binding protein, In: Spron MB, Roberts AB, Goodman DS (eds). The Retinoids Vol. 2, Orlando, FL, Academic Press 1984;42-89.  Back to cited text no. 9    
10.Bankson DD, Rifai N, Silverman LM. Serum retinol-binding protein and creatinine in onset of and recovery from acute renal failure. Clin Chem 1987;33(10):1942.  Back to cited text no. 10    
11.Lee BL, Chua SC, Ong HY, Ong CN. High-performance liquid chromatographic method for routine determination of vitamins A and E and beta-carotene in plasma. J Chromatogr 1992;581:41-7.  Back to cited text no. 11    
12.Abahusain MA, Wright J, Dickerson JW, El­Hazmi, MA, Aboul-Enein HY. Determination of retinol, 06-tocopherol, 06-and beta-carotene by direct extraction of human serum using high performance liquid chromatography. Biomed Chromatogr 1998;12:89-93.  Back to cited text no. 12    
13.Lucertini S, Valcavi P, Mutti A, Franchini I. Enzyme-linked immunosorbent assay of retinol-binding protein in serum and urine. Clin Chem 1984;30(1):149-51.  Back to cited text no. 13    
14.Cohen B. Observation of carotenemia. Ann Intern Med 1958;48(2):219-27.  Back to cited text no. 14    
15.Vannucchi MT, Vannucchi H, Humphreys M. Serum levels of vitamin A and retinol binding protein in chronic renal patients treated by continuous ambulatorial peritoneal dialysis. Int J Vitam Nutr Res 1992;62:107-12.  Back to cited text no. 15    
16.Yatzidis H, Digenis P, Fountas P. Hyper­vitaminosis A accompanying advanced chronic renal failure. Br Med J 1975;3:352-3.  Back to cited text no. 16    
17.Stewart WK, Fleming LW. Plasma retinol and retinol binding protein concentrations in patients on maintenance haemodialysis with and without vitamin A supplements. Nephron 1982;30:15-21.  Back to cited text no. 17    
18.Glover J, Moxley L Muhilal H, Weston S. Micro-method for fluorimetric assay of retinol-binding protein in blood plasma. Clin Chem Acta 1974;50:371-80.  Back to cited text no. 18    
19.Peterson PA. Demonstration in serum of two physiological forms of the human retinol binding protein. Eur J Clin Invest 1971;1:437-44.  Back to cited text no. 19    
20.Smith FR, Goodman DS. Vitamin A transport in human vitamin A toxicity. N Engl J Med 1976;294:805-8.  Back to cited text no. 20    
21.Gerlach TH, Zile MH. Upregulation of serum retinol in experimental acute renal failure. FASEB J 1990;4:2511-7.  Back to cited text no. 21    
22.Rask L, Anundi H, Bohme J, et al. The retinol-binding protein. Scand J Clin Lab Invest 1980;40:45-61.  Back to cited text no. 22    
23.Bernard A, Vyskocyl A, Mahieu P, Lauwerys R. Effect of renal insufficiency on the concentration of free retinol-binding protein in urine and serum. Clin Chim Acta 1988;171:85-93.  Back to cited text no. 23    
24.Kaplan LA, Stein EA, Willett WC, Stampfer MJ, Stryker WS. Reference ranges of retinol, tocopherols, lycopene and alpha- and beta-carotene in plasma by simultaneous high-performance liquid chromatographic analysis. Clin Physiol Biochem 1987;5:297-304.  Back to cited text no. 24    
25.Young DS. Implementation of SI units for clinical laboratory data. Ann Intern Med 1987;106:114-29.  Back to cited text no. 25    

Top
Correspondence Address:
Nora N Al-Nahedh
Department of Family and Community Medicine, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461
Saudi Arabia
Login to access the Email id


PMID: 18209407

Rights and Permissions



 
 
    Tables

  [Table - 1], [Table - 2]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Introduction
    Subjects and Methods
    Statistical Analysis
    Results
    Discussion
    Acknowledgement
    References
    Article Tables
 

 Article Access Statistics
    Viewed2498    
    Printed52    
    Emailed0    
    PDF Downloaded404    
    Comments [Add]    

Recommend this journal