|Year : 2014 | Volume
| Issue : 3 | Page : 94-97
Thyroid functions in Egyptian children with steroid responsive nephrotic syndrome: Relation to oxidative stress
Hekma Saad Farghaly1, Tahra Sherif2
1 Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Web Publication||13-Aug-2014|
Hekma Saad Farghaly
Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut
Source of Support: None, Conflict of Interest: None
Background : The interactions between kidney and thyroid functions have been known for many years; oxidative damage has been proposed as one of the possible mechanism involved in the nephrotic syndrome (NS). This study was done to find out the thyroid function of nephrotic children during nephrosis and to compare any significant changes of thyroid function status during nephrosis and remission in relation to oxidative stress markers. Patients and Methods: The study included 60 patients with steroid responsive NS (SRNS) and 30 children with matched age and sex as control. Cases were divided into three groups as follow, Group A: Include 35 patients with SRNS in relapse. Group B: Include 25 patients with SRNS in remission for periods ranging from 3 to 9 months, and not receiving steroid therapy. Group C: Include 30 children with matched age and sex as control. Methods: A thorough history and examinations, total serum thyroxine and triiodothyronine (TT4 and TT3) as well as serum free T4 (FT4), thyroid-stimulating hormone (TSH), and assessment of malondialdehyde (MDA) and total antioxidant capacity (TAC) levels as an oxidative stress markers were measured in all studied groups. Results: Serum TSH was significantly higher in patients with SRNS in relapse in comparison with patients with SRNS in remission and with control group (P < 0.001 in both), we found a significant decrease in TT4 and FT4 and TT3 and FT3 (FT3) concentrations in patients with SRNS in relapse in comparison with both cases with SRNS in remission and control group (P < 0.001 in both). MDA levels were significantly elevated, while TAC level was significantly decreased in patients with SRNS in relapse in comparison with patients with SRNS in remission and with control group (P < 0.001 in both). There was a positive correlation between serum TSH and plasma MDA and a negative correlation with FT4. Conclusions: The development of hypothyroidism in children with SRNS is associated with alteration in oxidant and antioxidant status. The biochemical hypothyroid state in relapse phase is temporary and improves with remission.
Keywords: Hypothyroidism, nephrotic syndrome, oxidative stress
|How to cite this article:|
Farghaly HS, Sherif T. Thyroid functions in Egyptian children with steroid responsive nephrotic syndrome: Relation to oxidative stress. Thyroid Res Pract 2014;11:94-7
|How to cite this URL:|
Farghaly HS, Sherif T. Thyroid functions in Egyptian children with steroid responsive nephrotic syndrome: Relation to oxidative stress. Thyroid Res Pract [serial online] 2014 [cited 2022 Jan 21];11:94-7. Available from: https://www.thetrp.net/text.asp?2014/11/3/94/138552
| Introduction|| |
Nephrotic syndrome (NS) is one of the most common renal diseases in the pediatric population. Its incidence is two to seven cases per 100,000 children below 16 years of age. About 90% of the NS is idiopathic and steroid-sensitive with a favorable prognosis, unfortunately around 60% of steroid responsive patients experience five or more relapse.  Oxidative damage has been proposed as one of the possible mechanism involved in the NS.  NS results in loss of plasma proteins and various other macromolecules in the urine leading to their deficiencies. Many of the physiologically important molecules which exist in the plasma, bound to plasma proteins, are also carried away and are lost in the urine.  Thyroid hormones (THs) are essential for normal metabolic function of the kidneys. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines'actions.  Studies of thyroid function in children with in relation to oxidative stress are lacking or few and controversial. 
Aim of the study
- Studying of thyroid function in children with either in relapse or remission in comparison with age-matched control.
- Assessment of malondialdehyde (MDA) and total antioxidant capacity (TAC) levels as an oxidative stress factors in children with NSin the remission phase as well as in relapse in comparison with age-matched control.
- Correlate oxidative stress marker (MDA) and thyroid function in children with NS in the relapse phase.
| Patients and methods|| |
This cross-sectional study was conducted Pediatric Department of Assiut University Children Hospital, Assiut, Egypt from September 2012 to August 2013. The work was approved from ethical scientific committee of Assiut Children University Hospital. An informed consent from the parents of children had been performed. The study included 60 patients (38 males and 22 females) presented to Pediatric Department of Assiut University Children Hospital, Assiut, Egypt with steroid responsive NS), 35 of them were in relapse and 25 in remission for periods between 3 and 9 months and not receiving steroid therapy. In addition, the study included 30 children with matched age and sex as control group. Diagnosis of NS was based on generalized edema, proteinuria (>40 mg/m 2 /h), hypoalbuminemia (serum albumin <2.5 g/dl), hypercholesterolemia (serum cholesterol >200 mg/dl). Remission was defined as urine albumin nil or trace (or proteinuria <40 mg/m 2 /h) for 3 consecutive days in early morning specimens. Relapse was defined as urine albumin 3 + or 4+ (or proteinuria >40 mg/m 2 /h) for 3 consecutive days in early morning specimens, having been in remission previously.  Any patient with hypertension, macroscopic hematuria, abnormal renal function, or the age of onset below 2 or above 8 years was excluded from the study. Cases were divided into three groups:
Included 35 patients with SRNS in relapse.
Included 25 patients with SRNS in remission for periods ranging from 3 to 9 months with no steroid therapy.
Control group C: Included 30 children with matched age and sex as control group.
- Age between 2 and 8 years.
- Documented NS.
- All patients were clinically euthyroid.
- Normal serum creatinine concentration
- Not receiving any formulations containing copper, zinc, selenium, or ascorbic
- NS occurring as a part of systemic disease
- Children receiving TH or any drug that affect TH
- Children with other endocrinal diseases
- Children with acute or chronic illness
- A thorough history was taken including data about onset and course of the disease, history of medications, and relapse. In addition, full clinical examination including blood pressure measurement for three consecutive days were done as well as full revision of patient's files.
- Thyroid stimulating hormone (TSH) serum level was determined by ultrasensitive immunometric assays (ImmuliteTM 2000 Third Generation, Diagnostic Products Corporation, Los Angeles, CA). Free thyroxine (FT4) and free triiodothyronine (FT3) were determined by radioimmunoassay (RIA) using an automated system (Roche Diagnostics) The reference range for TSH was 0.4-4.0 mU/L, for FT3 3.5-5.5 pmol/L, and for FT4 10.0-26.0 pmol/L. The coefficients of variations (CVs) were 5.0and 5.1% at TSH concentrations of 4.0and 10.0 mU/L, respectively. For FT4, the CV was 6.5% at 10.0 pmol/L and FT3 8.9% at 3.5 pmol/L.
- Estimation of plasma MDA were assayed by the thiobarbituric acid test 
- Serum TAC were colorimetrically measured according to the methods described by Koracevic et al.,  and Harma et al. 
Statistical Package for Social Sciences (SPSS), version 16 was used for data analysis. All data were expressed as the mean ± standard error of mean (SEM). Because of the small sample size and a propensity for outliers in some of the variables, differences between the groups were examined for statistical significance using the Mann-Whitney analysis. A P value of less than 0.05 denoted the presence of a statistically significant difference.
| Results|| |
[Table 1] shows some clinical and anthropometric characteristics of the studied groups, there was no difference in body weight, height, and body mass index among the studied groups.
|Table 1: Clinical and anthropometric characteristics of the studied groups |
Click here to view
[Table 2] shows TH levels in children with NS Children with NS in relapse have significantly higher level of TSH and significantly lower level T3, T4, FT3, and FT4 compared with either those in remission or control.
[Table 3] shows MDA and TAC in the studied groups. Children with NS in relapse have significantly higher level of MDA and significantly lower level TAC compared with either those in remission or control groups.
|Table 3: Plasma malondialdehyde and total antioxidants capacity in the studied groups |
Click here to view
[Figure 1] shows relationship between MDA and FT4 in replapse group; MDA have significantly − ve correlation with FT4.
|Figure 1: Figure 1: MDA levels have significantly -ve correlation with FT4. MDA: Malondialdehyde, FT4: Free thyroxine|
Click here to view
[Figure 2] shows relationship between MDA and TSH in replapse group; MDA levels have significantly + ve correlation with TSH.
|Figure 2: MDA levels have significantly +ve correlations TSH MDA: Malondialdehyde, TSH: Thyroid stimulating hormone|
Click here to view
| Discussion|| |
In the present study, cases with NS in relapse have significantly higher level of TSH and significantly lower level T4, FT4, T3, and FT3 compared with either those in remission or control. This was in agreement with the study conducted by Feinstein et al.,  who showed that the reduced serum levels of total T4 (TT4) and total T3 (TT3) in patients with NS may be to decreased binding to and/or concentration of serum carrier proteins. NS in relapse results in loss of plasma proteins and various other macromolecules in the urine leading to their deficiencies. Proteinuria results in loss of THs, most probably caused by loss of thyroxin-binding globulin. Proteinuria influence the activity of the pituitary-thyroid axis stimulating TSH production. 
In the present study, the findings of low levels of thyroxine in association with high levels of TSH suggest that a state of primary biochemical hypothyroidism exists in children with nephrotic children in relapse. The hypothyroidism is postulated to occur secondary to chronic massive proteinuria with loss of thyroid binding globulin and TH.  This temporary hypothyroid state improves with remission and needs no treatment.
Plasma MDA, which is a well-recognized biomarker of lipid peroxidation, was studied as a marker of tissue injury and oxidative stress.  In the present study, cases with NS in relapse (group A) have significantly higher levels of plasma MDA and significantly lower levels of TAC (with P < 0.001 for each) in comparison with cases in remission (group B) or control group (group C). This is in agreement with Zachwieja et al.,  who studied the total antioxidant status and mean antioxidant activity in 82 children with NS aged 4-16 years. They suggested that reduced antioxidant activity in NS may be related to lipid abnormalities. The imbalance between oxidative stress and antioxidant defense is believed to contribute to or even cause disease conditions.  Oxidative damage by the free radicals can lead to renal injury. Lipid peroxidation disrupts the structural integrity of the lipid bilayer, leading to increased membrane permeability and subsequent impaired electron transport for oxidative phosphorylation in mitochondria and increased lysosomal permeability. The increased permeability leads to the release of hydrolytic enzymes, further enhancing cell injury. 
In the present study, the antioxidant defense was evaluated by measuring TAC in serum. Total antioxidant activity as the most reliable factor is involved in antioxidation protection with NS.  The measurement of different antioxidant molecules separately is labor intensive, time consuming, and costly. Moreover, some investigators suggest that assessment of TAC of plasma may be more useful than measuring each antioxidants individually since their synergistic interaction could be determined. In our patients, cases with NS in relapse (group A) have significantly lower levels of TAC (with P <</i> 0.001 for each) in comparison with cases in remission (group B) or control group (group C). The antioxidant status of our patients further emphasizes oxidative stress as a significant determinant in occurrence of proteinuria among the children with NSin relapse.  Thus, to cut the progression of the adverse effects of oxidative stress combined antioxidant therapy may improve oxidation markers in children with NS in relapse.
In the present study, MDA correlated positively with TSH and negatively with FT4. These findings support the role of oxidative stress and development of thyroid abnormalities in children with NS in relapse. Children with NS in relapse generated oxidative stress and rapid formation of marked amounts of free MDA.  The increased circulating MDA level may act as the persistent metabolic signal for kidney damage and protein leakage including THs. 
| Conclusions|| |
The development of hypothyroidism in children with SRNS is associated with alteration in oxidant and antioxidant status. The biochemical hypothyroid state in relapse phase is temporary and improves with remission.
| References|| |
|1.||Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, et al. Steroid-sensitive nephrotic syndrome: From childhood to adulthood. Am J Kidney Dis 2003;41:550-7. |
|2.||Baud L, Ardaillou R. Involvement of reactive oxygen species in kidney damage Br Med Bull 1993;49621-9. |
|3.||Hatron PY, Wemeau JL, Guillemin R, Raviart B, Vanhille P, Devulder B. Thyroid function in the nephrotic syndrome. Rev Med Interne 1984;5:35-42. |
|4.||Iglesias P, Diez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol 2009;160:503-15. |
|5.||Sangita U, Chandran S, Almeida AF, Rajan G. Correlation between oxidative stress and thyroid function in patients with nephrotic syndrome. Int J Nephrol 2011;2011:256420. |
|6.||Mitarai T. Prevention and management of complications in nephrotic syndrome. Nippon Rinsho 2004;62:1893-7. |
|7.||Dawn-Linsley M, Ekinci FJ, Ortiz D, Rogers E, Shea TB. Monitoring thiobarbituric acid-reactive substances (TBARs) as an assay for oxidative damage in neuronal cultures and central nervous system. J Neurosci Methods 2005;141219-22. |
|8.||Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V. Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 2001;54:356-61. |
|9.||Harma M, Harma M, Erel O. Measurement of the total antioxidant response in preeclampsia with a novel automated method. Eur J Obst Gyn Reprod Biol 2005;11847-51. |
|10.||Feinstein EI, Kaptein EM, Nicoloff JT, Massry SG. Thyroid function in patients with nephrotic syndrome and normal renal function. Am Nephrol1982;2:70-6. |
|11.||Rajbala A, Sane AS, Zope J, Mishra VV, Trivedi HL. Oxidative stress status in children with nephrotic syndrome. Panminerva Med 1997;39:165-8. |
|12.||Zachwieja J, Bobkowski W, Dobrowolska-Zachwieja A, Zaniew M, Maciejewski M. Decreased antioxidant activity in hypercholesterolemic children with nephrotic syndrome. Med Sci Monitor 2003;6:2359. |
|13.||Fydryk J, Jacobson E, Kurzawska O, Ma³ecka G, Gonet B, Urasiñski T, et al. Antioxidant status of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 1998;12:751-4. |
|14.||Bulucu F, Vural A, Aydin A, Sayal A. Oxidative stress status in adults with nephrotic syndrome. Clin Nephrol 2000;53:169-73. |
|15.||Sawant BU, Nadkarni GD, Thakare U, Joseph LJ, Rajan MG. Changes in lipid peroxidation and free radical scavengers in kidney of hypothyroid and hyperthyroid rats. Indian Exp Biol 2003;41:1334-7. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]