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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 983-986

Hemoglobin A1c level in nondiabetic children with end-stage renal disease receiving regular hemodialysis


1 Department of Pediatric, Faculty of Medicine, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Clinical Pathology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
3 Department of Pediatric and Neonatology, Benha Children's Hospital, Benha, Egypt

Date of Submission16-Jan-2017
Date of Acceptance23-Apr-2017
Date of Web Publication31-Dec-2018

Correspondence Address:
Hend G Talha
Shebeen El-Kom, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_56_17

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  Abstract 


Objective
This study was designed to assess hemoglobin A1c (HbA1c) levels in nondiabetic children with end-stage renal disease (ESRD) receiving regular hemodialysis (HD).
Background
HbA1c level represents an established tool to monitor glycemic control in diabetic patients.
Patients and methods
We enrolled 30 nondiabetic ESRD children receiving HD as a HD group and 30 healthy children as a control group for this study. All children were subjected to full history taking and physical examination. HbA1c, fasting blood glucose, hemoglobin level, hematocrit value, serum calcium, potassium, phosphate, blood urea nitrogen, creatinine, and parathormone hormone were measured in all participants. HbA1c level was measured by using the turbidimetric immunoassay method.
Results
We found a statistically significant difference as regards HbA1c (%) between cases and controls. In addition, there was no statistically significant difference in fasting blood glucose (mg/dl) between the two studied groups.
Conclusion
Our limited data indicate that HbA1c levels are elevated in nondiabetic ESRD patients receiving HD.

Keywords: children, end-stage renal disease, hemodialysis, hemoglobin A1c


How to cite this article:
El-Mashad GM, Allam MM, El-Gebally ESI, Talha HG. Hemoglobin A1c level in nondiabetic children with end-stage renal disease receiving regular hemodialysis. Menoufia Med J 2018;31:983-6

How to cite this URL:
El-Mashad GM, Allam MM, El-Gebally ESI, Talha HG. Hemoglobin A1c level in nondiabetic children with end-stage renal disease receiving regular hemodialysis. Menoufia Med J [serial online] 2018 [cited 2019 Feb 20];31:983-6. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/983/248752




  Introduction Top


According to the national kidney foundation, chronic kidney disease (CKD) is defined as kidney damage for 3 months, or more clearly, the presence of structural or functional abnormalities in the kidney, with or without a decrease in glomerular filtration rate, manifested by pathologic abnormalities or markers of kidney damage such as microalbuminuria, abnormalities in the composition of blood or urine, or abnormalities in imaging tests[1].

CKD is characterized by an irreversible deterioration of renal function that gradually progresses to end-stage renal disease (ESRD). CKD has emerged as a serious public health problem. The incidence of CKD in children has steadily increased, with children from poor and ethnic minorities disproportionately affected[2].

The American Diabetic Association, the American Association of Clinical Endocrinology, and others recommend the quantification of glycohemoglobin in the form of hemoglobin A1c (HbA1c) for monitoring diabetic patients. A number of studies, including the Diabetes Control and Complication Trial and UK Prospective Diabetes Study, have shown that intensive glycemic control as assessed by HbA1c level can effectively delay the onset and the progression of retinopathy, nephropathy, and neuropathy in type 1 and type 2 diabetes mellitus (DM). A good glycemic control (HbA1c <7%) predicts better survival of diabetic ESRD patients who have started hemodialysis (HD) treatment[3].

The value of HbA1c for monitoring glycemic control in diabetic patients with ESRD receiving HD has been questioned because of the shortened red blood cell (RBC) life span and assay interference from uremia[4].

Falsely elevated HbA1c level were reported in severely uremic patients when HbA1c was measured by using the column chromatography method by the microchromatographic and macrochromatographic determinations or by using the electroendosmosis method. The major mechanism for elevated HbA1c level is that these assays fail to distinguish carbamylated hemoglobin (Hb) from glycohemoglobin in uremic patients. Immunoassay by using the turbidimetric method is a reliable and a widely used clinical laboratory method for measuring the HbA1c level. This method is not affected by the carbamylated Hb, chronic HD, anemia, polycythemia, and rheumatoid factor[5].

This study aimed to assess HbA1c levels in nondiabetic children with ESRD receiving regular HD turbidimetriclly.


  Patients and Methods Top


This cross-sectional, case–control study was carried out from May 2016 to November 2016 and was approved by the Ethics Committee of Faculty of Medicine, Menoufia University. All patients gave written consents to participate in this study. This study was carried out on 60 child divided into two groups.

Hemodialysis group (cases)

This group included 30 children with CKD on regular HD therapy (three times/week) attending to the Nephrology Unit in Pediatric Department at Menoufia University Hospital. There ages were in the range 3–18 years – 15 male patients and 15 female patients. Fifteen lived in rural areas and 15 in urban.

Control group (controls)

This group included 30 healthy children with age, sex, and residence matched with patients.

Inclusion criteria

Following were the inclusion criteria: age below18 years, both sexes, living in rural as well as urban areas.

ESRD with glomerular filtration rate more than 10 ml/min/1.73 m2, regular HD having at least three sessions per week, and duration of HD more than 3 months.

Exclusion criteria

Refusing and uncooperative patients or parents or those with other diseases affecting growth and development were excluded.

All were subjected to the assessment of full history and physical examination. HbA1c, fasting blood glucose, Hb, hematocrit, calcium, potassium, phosphate, blood urea nitrogen, creatinine, and parathormone hormone were investigated in both groups.

Method

Using infection control precaution, 3 ml of whole blood specimens in tubes containing EDTA were obtained from the ESRD patients group before HD in the morning and from the control group in the morning before breakfast. The control and test samples were measured at the same time to avoid interassay variation.

Reagents (R) used

R1: alkaline hematin reagent, R2: antibody reagent which is anti-HbA1c antibody, R3: polyhapten reagent (HbA1c polyhapten).

The apparatus used

Cobas 6000 (Roche Diagnostics, Indianapolis, IN, USA)

The first step was adding R1 to the sample to cleave the Hb from lysed erythrocyte, whereby N-terminal residue of β-chain of HbA1 fragments were released. Then R2, which is povine anti-human HbA1c monoclonal antibody, was added to attach to particle-bound HbA1c from the sample. Then R3 was added to react with the monoclonal povine anti-human HbA1c antibody to produce the agglutination reaction. The agglutination reaction mixture was monitored by turbidmetry with light-scattering signal at absorbance reading (540 nm) at a fixed interval chosen from the time-setting options available in the Cobas 6000 system software. Total Hb was determined by the use of a separate application file, whereby the hemolysate was mixed with the diluted alkaline hematin reagent and monitored with light-scattering signal at absorbance reading (410 nm) at a fixed interval chosen from the time-setting options available in the Cobas 6000 system software.

The final HbA1c result (expressed as percentage) was then calculated from HbA1c/total Hb ratio.

Statistical analysis

The data were expressed as mean ± SD. Student's t-test was used for statistical analysis and P value of less than 0.05 was considered statistically significant and P value of less than 0.001 was considered highly statistically significant. Data were collected, tabulated, and statistically analyzed using an IBM personal computer with statistical package for the social science (SPSS), version 20.


  Results Top


The mean age of studied cases was 13.1 ± 4.01 years – 15 (50%) male cases and 15 (50%) female cases. Fifteen (50%) lived in urban areas and 15 (50%) in rural. The mean age of controls was 13.3 ± 4.82 years – 15 (50%) male participants and 15 (50%) female participants. Fifteen (50%) lived in urban areas and 15 (50%) in rural. We can conclude that there was statistically nonsignificant differences between the studied groups regarding age, sex, and residence [Table 1].
Table 1: Demographic data of the studied groups

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There was statisitically significant statistical difference in HbA1c (%) between cases (5.8 ± 0.12%) and controls (5.1 ± 0.08%) (P < 0.001). Moreover, there was no statistically significant difference in fasting blood glucose (mg/dl) between the two studied groups: it was 78.5 ± 6.1 mg/dl in cases and 78.3 ± 6.34 mg/dl in controls (P = 0.901; [Table 2]).
Table 2: Hemoglobin A1c and fasting blood glucose in the studied groups

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In addition, there was no statistically significant correlation between HbA1c and the studied parameter in the two groups [Table 3].
Table 3: Correlation between hemoglobin A1c with studied parameters

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  Discussion Top


Hb undergoes glycation as a result of exposure to reducing sugars in the blood. Glycation is the nonenzymatic process of bonding glucose or fructose to a protein. This process occurs via a slow reaction that is irreversible. The degree of glycation increases in relation to the level of sugar in the blood and in relation to the age of the RBC in which the Hb is located[6].

Glycosylated HbA1c is the major form of all glycohemoglobin species in human blood. HbA1c reflects the average blood glucose level over the preceding 2–3 months. It is considered to be a useful marker of long-term glycemic control in patients with DM; moreover, it is used as a standard advocated by the American Diabetes Association for screening or diagnosing of DM among people[7].

This study was designed to assess HbA1c levels in nondiabetic children with ESRD receiving regular HD therapy.

We found no statistically significant difference between cases and controls regarding age and sex, as P value was 1.00 for both groups. This was in agreement with Wang et al.[5] who found no statistically significant difference as regards age and sex between cases and controls.

In this study, HbA1c was found to be significantly higher in cases than in controls (P < 0.001); this was in agreement with several studies such as by Wang et al.[5] and Sangeeta et al.[8]; both found that glycosylated hemoglobin levels are elevated in nondiabetic ESRD patients undergoing HD. Meshram et al.[9] observed that the HbA1c level is significantly higher (but within the normal range) in nondiabetic patients undergoing HD than in controls, and also observed that patients with CKD without HD may later land up into insulin resistance due to multitude of factors such as inflammation, oxidative stress, and elevated adipokines. Therefore, they suggested that monitoring HbA1c is not only important in diabetic or nondiabetic HD patients but also in CKD patients without HD. In the present study, no statistically significant difference were reported as regards fasting blood glucose in the two studied groups (P = 0.901); this was in agreement with Wang et al.[5] who found no statistically significant difference regarding fasting glucose levels and hematocrit between the studied groups. Sangeeta et al.[8] found that random blood glucose had no significant difference in both studied groups[5],[8].

Our study found no statistically significant correlation between HbA1c and other studied parameters in the two studied groups. This was in line with many other studies such as Kuo et al.[10], Sangeeta et al.[8], and Schiel et al.[11]: they observed that HbA1c levels were elevated significantly in ESRD patients with no significant correlation with blood glucose levels, thus indicating true glucose intolerance.

The mechanisms of elevated HbA1c level in nondiabetic ESRD patient receiving HD can be attributed to repetitive exposure of RBC to high glucose level in the dialysate during HD, as our patients had HD three times a week and 4–6 h in each dialysis against a dialysate containing 200 mg/dl glucose. Sam et al.[12] suggested that the dialysate should contain adequate amount of glucose because if dextrose is used in dialysate there may be risk for triglyceridemia. The second possibility is that the patients with ESRD have glucose intolerance. Factors that can affect the values of HbA1c in ESRD patients, such as shortened life span of RBC (decrease HbA1c level), anemia (increase HbA1c level), and uremia, were not considered because the usage of the turbidimetric immunoassay method for HbA1c estimation suppresses these factors up to certain limits; therefore, we cannot deny a possibility that an independent impact of glycemic control on nondiabetic HD patients may be somewhat different. Moreover, by using this method, no correlation was found between HbA1c and other studied parameters. Sangeeta et al.[8] suggested that HbA1c may be an important target for intracellular glycoxidation and peroxidation reactions that result in the formation of advanced glycation end products, which are further implicated in the causation and the progression of atherosclerosis and chronic deranged glycemic control in these patients[12].


  Conclusion Top


HbA1c may be used as a marker of impaired glucose metabolism and glycemic control in nondiabetic patients with ESRD receiving regular HD, and thus is necessary to prevent future complications in these patient.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
El Bahanasy RE, Mahrous OA, Abu Salem ME, El Batanony MA, Mourad WS, Kasemy ZA. The role of microalbuminuria in population screening for chronic kidney disease in an Egyptian village. Menoufia Med J 2013; 26:18–22.  Back to cited text no. 1
    
2.
Whyte DA, Fine RN. Chronic kidney disease in children. Pediatr Rev 2008; 29:335–341.  Back to cited text no. 2
    
3.
Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, Di Meglio LA, et al. Current state of type 1 diabetes treatment in the U.S: updated data from the T1D Exchange clinic registry. Diabetes Care 2015; 38:971–978.  Back to cited text no. 3
    
4.
Hammouda AM, Mady GE. Correction formula for carbamylated hemoglobin in diabetic uremic patients. Ann Clin Biochem 2001; 38:115–119.  Back to cited text no. 4
    
5.
Wang X, Peesapati SK, Renedo MF, Moktan S. Hemoglobin A1c levels in non-diabetic patients with end-stage renal disease receiving hemodialysis. J Endocrinol Invest 2004; 27:733–735.  Back to cited text no. 5
    
6.
Oppenheimer M, Jensen R, Huntington MK. When 7 isn't 7: glycohemoglobin and chronic kidney disease. S D Med 2013; 66:59–61.  Back to cited text no. 6
    
7.
Li L, Zang W, Zhang X. A high-through put method for measurement of glycohemoglobin in blood samples utilizing laser-accelerated proteolysis and MALDI-TOF MS. Anal Bioanal Chem 2016; 408:1507–1513.  Back to cited text no. 7
    
8.
Sangeeta K, Lal AK, Gulshan M. Glycosylated haemoglobin in non-diabetic end-stage renal disease patients undergoing haemodialysis. J Clin Diagn Res 2010; 4:3191–3195.  Back to cited text no. 8
    
9.
Meshram A, Khare R, Moahajan SN. Glycemic status in diabetic and non-diabetic ESRD patients with or without hemodialysis in rural hospital of Central Maharashtra. Int J Med Sci 2014; 3:219–223.  Back to cited text no. 9
    
10.
Kuo IC, Lin HY, Niu SW, Hwang DY, Lee JJ, Tsai JC, et al. Glycated hemoglobin and outcomes in patients with advanced diabetic chronic kidney disease. Sci Rep 2016; 6:20028.  Back to cited text no. 10
    
11.
Schiel R, Heinrich S, Steiner T, Ott U, Stein G. Post-transplant diabetes mellitus risk factors, frequency of transplant rejections and long term prognosis. Clin Exp Nephrol 2005; 9:164–169.  Back to cited text no. 11
    
12.
Sam R, Vaseemuddin M, Leong WH, Rogers BE, Kjellstrand CM, Ing TS. Composition and clinical use of hemodialysates. Hemodial Int 2006; 10:15–28.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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