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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1374-1381
Impact of patient counseling on treatment adherence behavior and quality of life in maintenance hemodialysis patients


1 Department of Cellular and Molecular Biology Institute of Biology, University of Sciences and Technologies Houari Boumedienne, Algiers, Algeria
2 Department of Biochemistry, Central Laboratory of Biology, Algiers, Algeria
3 Department of Nephrology, N'Fissa Hamoud Hospital, Algiers, Algeria
4 Pierre et Marie Curry Center, Endocrinology Laboratory, Algiers, Algeria
5 Department of Biochemistry, Central Laboratory of Biology, Bainem Hospital, Algiers, Algeria

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Date of Web Publication4-May-2022
 

   Abstract 


Kidney transplantation is the best treatment received by an uremic patient. One of the major advantages of transplantation is restoring a hormonal profile as before the chronic kidney disease. However, the posttransplant state depends on several factors including the quality of the graft. In this study, we assessed the donor age in living donors-recipients as well as the exploration of their hormonal profile. This is a single-center follow-up study over a period of 3 years, including 90 kidney recipients transplanted by living donors. We performed blood measurements of parathyroid hormone, prolactin, follicle stimulating hormone, luteinizing hormone, testosterone, estradiol, blood glucose, urea, creatinine, total cholesterol, triglycerides, high density lipoprotein-cholesterol, uric acid, albumin, and 24-h proteinuria. Glomerular filtration rate, body mass index, and low-density cholesterol were calculated. To analyze the donor age effect on recipients, the patients were divided into two groups according to donors age (<40 years and ≥40 years). The hormonal profile was normal for almost the majority of patients. In addition, we noted a return to dialysis associated with certain metabolic abnormalities and a donor age >40 years. Exploring the hormonal profile of the recipient is recommended. The donor age significantly influences the recipient fate but not their hormonal profile.

How to cite this article:
Djebli-Azzal N, Benazzoug Y, Arab M, Rayane T, Abib L, Cherifi ME. Impact of patient counseling on treatment adherence behavior and quality of life in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl 2021;32:1374-81

How to cite this URL:
Djebli-Azzal N, Benazzoug Y, Arab M, Rayane T, Abib L, Cherifi ME. Impact of patient counseling on treatment adherence behavior and quality of life in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1374-81. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1374/344757



   Introduction Top


Having reached end-stage renal disease (ESRD), transplantation is the best treatment for the patient.[1] Among its main advantages, we find the restoring of hormonal profile and patient quality of life, allowing the patient to recover sexuality and fertility lost during uremia.[2]

The kidneys play an important role in the homeostasis of several hormones such as their excretion or their biodegradation. The kidney transplantation (KT) is the only ESRD treatment that can correct the majority of endocrine disturbances associated with uremia. However, other hormonal abnormalities persist despite the KT. Among the factors maintaining these hormonal imbalances, the uremia duration, the graft function as well as the alteration of the target organs reactivity to hormones induced by immunosuppressive drugs, which will result in the modulation of secretion, transport, and breakdown of hormones. In addition, acute rejection episodes may play a role in alteration of the endocrine system.[3]

Graft quality determines survival and long-term graft status, which is directly related to the donor age.[4] The clinicobiological characteristics of the donors as well as the state of the graft determine its survival. Grafts that are derived from living donors are associated with fewer postoperative complications and good graft function and survival compared to those obtained from deceased donors. Even the cardiovascular status of living donor-recipients is better after a KT compared to that performed from deceased donors.[5] The donor age is among the most important risk factors related to a poor prognosis of the recipient after KT,[6] it is even a limiting factor of the graft lifespan whatever its origin.[7]

The two main objectives of this study carried out at the CHU N’Fissa Hamoud-Algeries, were on the first hand to explore the hormonal profile of kidney transplant recipients from living donors, and on the other hand, to study the influence of the living donor age on clinicobiological parameters.


   Patients and Methods Top


Study population

It is an analytical, prospective, monocentric follow-up study span over a period of the years from January 2015 to January 2018. The study involved 90 recipients transplanted for more than eight months. Patients under the age of 16 years or transplanted from deceased donors were excluded from the study. All patients were transplanted for the first time and had been treated by hemodialysis. The clinical characteristics of recipients were collected from medical files and questionnaires which included age, sex, weight, height, personal and family history, initial nephropathy, modalities and duration of dialysis, KT duration, smoking, presence or absence of comorbidity such as diabetes mellitus. In addition, the age, gender, history, and current health status of donors were recorded. Consent was taken from all included recipients.

All recipients were treated with an calcineurin inhibitor (cyclosporine A or tacrolimus) as a base treatment associated with myco-phenolate mofetil and corticosteroids.


   Methods Top


Blood samples were taken in the morning after an overnight fasting (between 8 and 12 h fasting), collected on dry and heparinized tubes (lithium heparin).

The parathyroid hormone (PTH) assay was carried out by immunoradiometric assay with Iodine 131 as a marker. The prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol assays were performed by immunological methods (electrochemiluminescence) using a Roche-Cobas® device-Switzerland. The t-test was only performed for men over the age of 20 years. The estradiol testing has only been done in postmenopausal and peri-menopausal women.

Colorimetric enzymatic methods were used for the determination of blood glucose (Gly), uric acid (UA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and urea. Creatinine (Cr) was determined by a kinetic method using the jaffe reagent. The 24-h proteinuria and albumin were performed by colorimetric techniques. We used a SIEMENS type Dimension® clinical chemistry system automation for all these parameters.

Low-density lipoprotein cholesterol (LDL-c) was calculated by the Friedewald formula:[8] LDL = TC –- [(TG/5) + HDL-c].

Body mass index (BMI) was calculated by the formula codified by the World Health Organization.[9]

Glomerular filtration rate (GFR) was calculated by the formula modified diet in renal diseases defined in 1999 by Levey et al.[10]

We evaluated the graft function by urea, Cr, Cr 1-year post-KT, GFR, 24-h proteinuria, UA, rejection, and a return to chronic dialysis.

Hyperparathyroidism is defined, according to the reference values of our study, by a rate greater than 76 Ppg/mL.

The transplant patients were randomized into two groups according to the donor age, donors under 40 years, and donors aged 40 years or older.


   Statistical Analysis Top


All continuous variables are expressed as mean ± standard deviation (SD) or median (25%–75% quartiles), and categorical variables are presented as a percentage. The normality distribution of the variables was examined by the W-Shapiro–Wilk test. The statistical analysis consisted of a Student’s t-test for independent samples when the distribution is normal, the Mann–Whitney U-test was used in case of skewed distribution. To analyze associations between different variables, the non-parametric Spearman’s correlation was used. To study the influence of donor age on graft survival, we used the Kaplan–Meier test. A P <0.05 was considered to be statistically significant. The statistical study was performed using the IBM SPSS Statistics software version 20.0 (IBM Corp., Armonk, NY, USA).


   Results Top


Among 90 patients included in this study, 54 (60%) were male. At inclusion, their mean age was 34.69 ± 10.92 years, with extremes ranging from 16 to 65 years. The mean duration of KT was 42.48 ± 32.56 months. The mean ± SD of BMI and GFR were respectively 21.74 ± 4.39 kg/m2 and 53.39 ± 21.81 mL/min/1.73 m2. Sixteen (15.5%) of our patients were smokers and 69 (76.4%) of them received tacrolimus. For donors, the mean age was 44.22 ± 12.8 years with extremes ranging from 21 to 73 years. The initial nephropathies of our patients as well as other clinical features of the participants are shown in [Table 1]. After three years of follow-up, 11 (12.22%) of patients made a return to chronic dialysis and five (5.55%) of them died [Table 1].
Table 1: Demographic and clinical characteristics of kidney recipients.

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The hormonal profile of patients is summarized in [Table 2].
Table 2: The hormonal profile of kidney recipients.

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Although the medians were normal, 43 (47.77%) patients showed hyperparathyroidism and two patients (18.1%) are hypo-gonadic (testosterone < 10 nml/L).[11] Furthermore, five patients (55.5%) had an excessively high rate of estradiol (136.7 ± 51.73 pg/mL) and two (22.2%) had values below <5 pg/mL.

By comparing estradiol levels depending on serum Cr concentrations, we have noted a decrease level of this hormone in women with Cr levels greater than 15 mg/L (15.94 ± 22 pg/mL vs. 153.16 ± 98 pg/mL; P = 0.02).

Hyperprolactinemia was observed in 17 men (37.77%) and seven women (23.33%). We have noted an increased level in FSH (>12 mMI/mL) in three men (6.66%). LH levels were elevated (>8.5 mMI/mL) in 15 (33.33%) men and seven (23.33%) women (>58.5 mMI/ mL). High plasmatic concentration of PTH was seen in patients who returned to chronic dialysis compared to those who were stable (189.02 ± 59.0 pg/mL vs. 86.61 ± 77.48 pg/mL, P = 0.01). Among the 5 deaths noted (4 women and 1 man) at the end of the follow-up, 2 women had a collapsed estradiol level compared to living transplanted women (P = 0.007).

[Table 3] shows the comparison between the studied parameters of kidney transplants according to the donor age. The hormonal parameters studied, in this case PTH, LH, FSH, prolactin, testosterone, and estradiol show no significant difference. After one year of KT, the Cr concentration of recipients was greater than 15 mg/L in 11 (37.93%) recipients transplanted from donors over 40 years of age, while in the other group, serum Cr levels were normal. At the end of the study, even (17.5%) recipients from donors over 40 years made a return to chronic dialysis, while in the other group, no return has been reported (P = 0.03).
Table 3: Influence of donor age on studied parameters of transplanted patients.

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No significant differences emerged between the two groups concerning the other biochemical and clinical parameters (TC, TG, LDL-c, HDL-c, BMI, CVD, HTA, and diabetes). Strong and positive correlations were seen between the donor age and urea, Cr, Cr 1 -year post KT as well as for UA [Table 4].
Table 4: Correlations between the donor's age and the parameters of the graft function.

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For graft survival related to donor age (Kaplan–Meier), the difference between the two groups was not significant (P = 0.09), however, between eight patients who returned to chronic dialysis 7 of their donors were >40.


   Discussion Top


The consequences of chronic uremia are well known. KT, the gold standard in the treatment of ESRD, can correct mostmetabolic and tissue abnormalities. In addition, one of the main objectives of transplantation is restoring the same sexuality and fertility as before kidney disease. However, the latter’s success depends on several factors, the most important of which is the donor’s age.

The two main objectives of this work were, on the one hand, to demonstrate the influence of the living donor age on the Algerian KT recipients, and on the other hand, to assess the hormonal profile of this same population.

All studied hormonal values were within the reference ranges with an exception for the PTH. It should be noted that our patients suffered from hyperparathyroidism during the pretransplant period, and only 52.23% of them were able to restore normal parathyroid function after KT. Knowing that hyperpara-thyroidism was defined by PTH values above the upper limit of the reference interval.

Indeed, 43 (47.77%) patients had hyperpara-thyroidism. Although KT quickly restores kidney function and the ability to respond to hyperparathyroidism, 20%–30% of patients show resistance due, to inhibitory feedback, which persists several years after transplant.[12] It is tertiary hyperparathyroidism or persistent hyperparathyroidism after KT.[13]

The persistence of this abnormality contributes to mineral-bone disorders[14] which are significantly associated with morbidity and mortality in KT.[15] Posttransplant hyperpara-thyroidism is highly dependent on the dialysis duration, the severity of hyperparathyroidism, and/or Vitamin D supplementation.[16] In addition, we found hyperparathyroidism in 12 patients who returned to chronic dialysis. Published studies have concluded that this disorder is an independent risk factor for graft loss and mortality after KT.[15]

The restoration of the hypothalamic-pituitary axis, and therefore, a normal hormonal profile, after KT is mainly influenced by graft efficiency and good health condition.[17],[18]

Hypogonadism, defined by low testosterone values, is frequently observed in patients with end-stage renal failure and hemodialysis. KT greatly improves testosterone levels.

However, this does not apply to all transplant recipients due to many factors including the suppression of gonadal function by the immunosuppressants effect on the hypo-thalamic-pituitary axis,[19] advanced age, BMI and high waist circumference.[20] In our study, two of 33 males patients (6.06%) had low levels of testosterone; this percentage remains very low to other studies which have estimated it at 18% or more.[20] This may be due to the young age and the low BMI of our population compared to the other.

Among the nine postmenopausal and peri-menopausal patients, serum levels of estradiol were high in five (55.55%) of them. The peri-menopausal state is characterized by unstable hormonal fluctuations;[21] this may explain the values found in our study. Two deceased patients had rates below 5 pg/mL. This hormone reached very low levels in patients whose serum Cr exceeded the upper limits, and conversely in patients with elevated estradiol levels, serum Cr was within the norm. This is consistent with studies which demonstrated that this hormone had a protective role on the kidneys of some animals.[22]

Increased serum levels of LH and FSH were found in men, while in women, only LH level was elevated. In their study, Kassmann et al showed that FSH and LH levels often remain high in male transplant recipients, and they also noted a return to normal testosterone concentration.[23] The increased LH concentration observed in seven female patients could be explained by the drop in estradiol, hormone with a negative feedback on gonadotropins in the normal state.[24] Hyperprolactinemia was observed in 17 male (37.77%) transplanted recipients and in seven women (23.33%). Ferraris et al showed in their study hyper-prolactinemia in 35% of transplant recipients with more pronounced values in men compared to women.[25]

The age of the donors plays a crucial role in the future of the graft. Randomization of transplants based on donor age (<40 years and ≥0 years) shows a significant difference between the two groups for parameters exploring graft function, return to dialysis, and glucose [Table 3]. All studied parameters were higher in transplants from older donors with the exception of GFR and glucose. For this last parameter, although it is lower in transplants from older donors, it remains within physiological limits. It must be emphasized that despite the nonsignificant differences in graft survival compared to the two donor groups studied (P = 0.09), eight patients making return to chronic dialysis, seven from their donors were >40 years old.

Several studies have already investigated kidney transplants from older donors, whether living or deceased donors, all of whom have concluded that the donor’s age is a limiting factor in graft function and its long-term survival.[7] This is one of the most important independent risk factors associated with lower outcomes after KT.[6] This is explained by aging that affects all the human organs including the transplanted organ. The damage caused by the physiological aging of this organ negatively affects the transplantation results.[26] On the other hand, vasculopathies are elevated in the kidneys from older donors which reduce their capacity to deal with kidney problems that may emerge.[6] According to previous studies, the advanced donor age influences the function of the graft, just after transplantation by a delayed recovery of graft function[27] and also influences its long-term functioning and even its survival.[28] According to Zhou et al, this biological phenomenon (a reduction in renal function linked to the advanced donor age) can reduce graft survival, predispose it to ischemia and nephrotoxicity, cause a decrease in regeneration of the organ and has a high degree of immunogenicity.[29] It should be added that in a recent study, the advanced donor age influences even the arterial rigidity of the transplant.[30]

The mean value of UA was significantly different between the two studied groups. UA is the end product of purine catabolism, excreted mainly by the kidneys. In our study, hyperuricemia was observed in transplant recipients whose donors were aged >40 years. Authors have demonstrated that hyperuricemia is observed in transplant recipients whose graft function is impaired.[31] Hyperuricemia has been associated too, in many publications, with oxidative stress that will promote the deterioration of the graft.[32]


   Conclusion Top


Although the hormonal profile of Algerian transplant recipient seems normal, its exploration is recommended. The donor age significantly influences the outcome of the graft but does not show any influence on the hormonal profile of the recipients. Unfortunately, action on on the donor age factor is limited because of family relationships where the elderly are usually the majority of donors. Other studies are being carried out to better understand the state of the KT in Algeria.


   Acknowledgments Top


We would like to thank the transplant teams in CHU N’Fissa Hamoud, Algeries, Dr. M. Slimani, Dr. Issolah, and Miss M. Sellam for their valuable contribution to KT activities.

Conflict of interest: None declared.



 
   References Top

1.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999;341:1725-30.  Back to cited text no. 1
    
2.
Raggi MC, Siebert SB, Friess H, Schremmer-Danninger E, Thorban S, Dinkel A. Sexual and relationship functioning before and after renal transplantation: A descriptive study with patients and partners. Scand J Urol Nephrol 2012;46:431-6.  Back to cited text no. 2
    
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Kokot F, Wiecek A. Function of endocrine organs in kidney transplant patients. Ann Transplant 1996;1:23-8.  Back to cited text no. 3
    
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Legendre C, Canaud G, Martinez F. Factors influencing long-term outcome after kidney transplantation. Transpl Int 2014;27:19-27.  Back to cited text no. 4
    
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Yazbek DC, De Carvalho AB, Barros CS, et al. Cardiovascular disease in early kidney transplantation: Comparison between living and deceased donor recipients. Transplant Proc 2012;44:3001-6.  Back to cited text no. 5
    
6.
Watson CJ, Johnson RJ, Birch R, Collett D, Bradley JA. A simplified donor risk index for predicting outcome after deceased donor kidney transplantation. Transplantation 2012; 93:314-8.  Back to cited text no. 6
    
7.
Noppakun K, Cosio FG, Dean PG, Taler SJ, Wauters R, Grande JP. Living donor age and kidney transplant outcomes. Am J Transplant 2011;11:1279-86.  Back to cited text no. 7
    
8.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.  Back to cited text no. 8
    
9.
WHO. Use and Interpretation of Anthropometry WHO Report. Technical Report Series No. 854. Geneva: WHO; 1995.  Back to cited text no. 9
    
10.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70.  Back to cited text no. 10
    
11.
Albaaj F, Sivalingham M, Haynes P, et al. Prevalence of hypogonadism in male patients with renal failure. Postgrad Med J 2006;82: 693-6.  Back to cited text no. 11
    
12.
Evenepoel P, Claes K, Kuypers D, Maes B, Bammens B, Vanrenterghem Y. Natural history of parathyroid function and calcium metabolism after kidney transplantation: A single-centre study. Nephrol Dial Transplant 2004;19:1281-7.  Back to cited text no. 12
    
13.
Cruzado JM, Moreno P, Torregrosa JV, et al. A randomized study comparing parathyroi-dectomy with cinacalcet for treating hypercalcemia in kidney allograft recipients with hyperparathyroidism. J Am Soc Nephrol 2016; 27:2487-94.  Back to cited text no. 13
    
14.
Baker LR, Abrams L, Roe CJ, et al. 1,25(OH)2D3 administration in moderate renal failure: A prospective double-blind trial. Kidney Int 1989;35:661-9.  Back to cited text no. 14
    
15.
Pihlstrøm H, Dahle DO, Mjøen G, Pilz S, Marz W, Abedini S, et al. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism. Transplantation 2015;99:351-9.  Back to cited text no. 15
    
16.
Wolf M, Weir MR, Kopyt N, et al. A prospective cohort study of mineral metabolism after kidney transplantation. Transplantation 2016;100:184-93.  Back to cited text no. 16
    
17.
Kim JH, Chun CJ, Kang CM, Kwak JY. Kidney transplantation and menstrual changes. Transplant Proc 1998;30:3057-9.  Back to cited text no. 17
    
18.
Pietrzak B, Cyganek A, Jabiry-Zieniewicz Z, et al. Function of the ovaries in female kidney transplant recipients. Transplant Proc 2006; 38:180.  Back to cited text no. 18
    
19.
Tondolo V, Citterio F, Panocchia N, et al. Gonadal function and immunosuppressive therapy after renal transplantation. Transplant Proc 2005;37:1915-7.  Back to cited text no. 19
    
20.
Reinhardt W, Kübber H, Dolff S, Benson S, Führer D, Tan S. Rapid recovery of hypo-gonadism in male patients with end stage renal disease after renal transplantation. Endocrine 2018;60:159-66.  Back to cited text no. 20
    
21.
Prior JC. Ovarian aging and the perimenopausal transition: The paradox of endogenous ovarian hyperstimulation. Endocrine 2005;26: 297-300.  Back to cited text no. 21
    
22.
Shanhua M, Hua X, Lujia Z, et al. Estrogen preserves split renal function in a chronic complete unilateral ureteral obstruction animal model. Exp Ther Med 2014;7:1555-62.  Back to cited text no. 22
    
23.
Kassmann K, Arsan A, Sharer K, Broyer M. Gonad function and sexual activity in male renal transplant patients. Ann Pediatr (Paris) 1991;38:405-6.  Back to cited text no. 23
    
24.
Zingraff J, Jungers P, Pélissier C, Nahoul K, Feinstein MC, Scholler R. Pituitary and ovarian dysfunctions in women on haemodialysis. Nephron 1982;30:149-53.  Back to cited text no. 24
    
25.
Ferraris JR, Domene HM, Escobar ME, Caletti MG, Ramirez JA, Rivarola MA. Hormonal profil in pubertal females with chronic renal failure: Before and under haemodialysis and after renal transplantation. Eur J Endocrinol 1987;115:289-96.  Back to cited text no. 25
    
26.
Slegtenhorst BR, Dor FJ, Elkhal A, et al. Mechanisms and consequences of injury and repair in older organ transplants. Transplantation 2014;97:1091-9.  Back to cited text no. 26
    
27.
Sekta S, Ziaja J, Kolonko A, et al. Donation and transplantation of kidneys harvested from deceased donors over the age of 60 years in the upper Silesia region. Transplant Proc 2016;48: 1466-71.  Back to cited text no. 27
    
28.
Summers DM, Johnson RJ, Hudson A, Collett D, Watson CJ, Bradley JA. Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: A cohort study. Lancet 2013;381:727-34.  Back to cited text no. 28
    
29.
Zhou XJ, Rakheja D, Yu X, Saxena R, Vaziri ND, Silva FG. The aging kidney. Kidney Int 2008;74:710-20.  Back to cited text no. 29
    
30.
D’Halluin P, Bertin S, Gatault P, et al. Donor age, lukewarm ischemia and immunosuppressive treatments have an impact on arterial stiffness in renal transplant patients Néphrol Thér 2016;12:283.  Back to cited text no. 30
    
31.
Weng SC, Shu KH, Tarng DC, et al. Uric acid is highly associated with kidney allograft survival in a time-varying analysis. Transplant Proc 2014;46:505-10.  Back to cited text no. 31
    
32.
Perico N, Codreanu I, Caruso M, Remuzzi G. Hyperuricemia in kidney transplantation. In: Ronco C, Rodeghiero F, editors. Hyperuricemic Syndromes: Pathophysiology and Therapy. Vol. 147. Contrib Nephrol. Basel, Karger; 2005. p. 124-31.  Back to cited text no. 32
    

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Correspondence Address:
Nadia Djebli-Azzal
Institute of Biology, University of Sciences and Technologies Houari Boumedienne, Algiers
Algeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.344757

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    Abstract
   Introduction
   Patients and Methods
   Methods
   Statistical Analysis
   Results
   Discussion
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