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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 6  |  Page : 1205-1209
The correlation between attention deficit hyperactivity disorder and steroid-dependent nephrotic syndrome


1 Department of Pediatric Nephrology, Amir-Kabir Hospital, Arak, Iran
2 Department of Psychiatry, Arak University of Medical Sciences, Arak, Iran
3 Department of Basic Sciences, Arak University of Medical Sciences, Arak, Iran
4 Department of Pediatrics, Arak University of Medical Sciences, Arak, Iran

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Date of Web Publication30-Oct-2015
 

   Abstract 

Nephrotic syndrome (NS) is characterized by nephritic-range proteinuria and the triad of clinical findings associated with large urinary losses of protein, hypoalbuminemia, edema and hyperlipidemia. More than 80% of children below 13 years of age with primary NS have steroid-responsive forms. There is no identifiable cause of attention-deficit hyperactivity disorder (ADHD). It is likely that the symptoms of ADHD represent a final common pathway of diverse causes, including genetic, organic and environmental etiologies. This case-control study was performed on 130 children aged between 5 and 13 years who were followed-up for two years. Sixty-five children with steroid-dependent nephrotic syndrome (SDNS) as the case group and 65 healthy children as the control group were included in the study. Patients with minimal change NS were treated with prednisolone for at least six months. Conner's Parent Rating Scale - 48 (CPRS-48) was completed by the parents and the children were identified with any form of ADHD. Then, children were referred to an expert psychiatrist. The collected data were analyzed with SPSS software. The result showed that there was no significant relationship between different types of ADHD in both groups. Thus, based on current study, one may conclude that there are no significant differences between prevalence of ADHD in children with SDNS and the control group.

How to cite this article:
Yousefichaijan P, Salehi B, Rafiei M, Dahmardnezhad M, Naziri M. The correlation between attention deficit hyperactivity disorder and steroid-dependent nephrotic syndrome. Saudi J Kidney Dis Transpl 2015;26:1205-9

How to cite this URL:
Yousefichaijan P, Salehi B, Rafiei M, Dahmardnezhad M, Naziri M. The correlation between attention deficit hyperactivity disorder and steroid-dependent nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Dec 3];26:1205-9. Available from: https://www.sjkdt.org/text.asp?2015/26/6/1205/168624

   Introduction Top


Nephrotic syndrome (NS), a manifestation of glomerular disease, is characterized by nephrotic-range proteinuria and the triad of clinical findings associated with large urinary losses of protein, hypoalbuminemia, edema and hyperlipidemia. [1],[2],[3] Nephrotic-range proteinuria is defined as protein excretion of >40 mg/m 2 /h or a first morning protein:creatinine ratio of >2- 3: 1. Because more than 80% of children under 13 years of age with primary NS have steroid-responsive forms [mainly, minimal change nephrotic syndrome (MCNS)], steroid therapy may be initiated without a renal biopsy if a child has typical features of NS. [4],[5],[6],[7] Over 90% of children who respond to steroids do so within four weeks. Responders should receive steroids for 12 weeks. A subset of patients relapses when they are put on alternate-day steroid therapy or within 28 days of completing a successful course of prednisone therapy. Those with two consecutive relapses are termed steroid dependent.

Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder with diverse etiology and manifests with symptoms of inattention, hyperactivity and impulsivity. There is evidence that ADHD runs in some families, but there is no evidence of any single gene that determines ADHD type. Although most cases of ADHD occur typically in normally developing children, ADHD can also be seen in children who have developmental disorders, including fetal alcohol syndrome and Down's syndrome, as well as in children who have had varying levels of brain injury, including perinatal brain damage. Most commonly, there is no identifiable cause of ADHD. It is likely that the symptoms of ADHD represent a final common pathway of diverse causes, including genetic, organic and environmental etiologies. [1]


   Materials and Methods Top


This case-control study was performed on 130 children (56% male in the case group and 67% male in the control group) in the age bracket of 5-13 years who were referred to the pediatric nephrology clinic of the Amir Kabir Hospital in Arak, Iran, in 2012-2013. The age at onset of disease was 5-13 years and the duration of follow-up was two years. Of the 130 children included in the study, 65 children with steroid-dependent nephrotic syndrome (SDNS) were considered as the case group and 65 healthy children who did not have SDNS were chosen as the control group. Patients with MCNS were treated with prednisolone 2 mg/kg/day or 60 mg/m 2 /24 h, maximum 60 mg/day administered once a day or split into multiple doses. Responders received steroids for 12 weeks. The time of treatment with prednisolone was for at least six months. The sample number was calculated with the COHEN FORMULA.

Clinical interviews were carried out with the children and their parents to evaluate the inclusion/exclusion criteria in each case. This was performed to study the confounding factors among the children and their parents that may contribute to ADHD in children, which included the following:

  1. History of major depressive disorder (MDD), schizophrenia, autistic disorders (ASD), Tourette's disorder, bipolar disorder (BD), ADHD and other likely psychiatric disorders.
  2. Congenital and chromosomal abnormalities such as Down's syndrome and Fetal alcohol syndrome, birth weight <1500 g or very low birth weight (VLBW), major and chronic maternal diseases in pregnancy, the use of teratogenic drugs, alcohol, substance and smoking by the mother during pregnancy (particularly in the first three months).
  3. Substance abuse, mental retardation (MR).
  4. Epilepsy, asthma, diabetes, immune deficiency, organ transplantation, a history of moderate to severe head trauma and other considerable or chronic medical disorders.
  5. History of chronic medication use in children.
  6. Family history [first-degree relatives (parents and siblings)] of major psychiatric diseases such as AD, schizophrenia, depresssion, ADHD, etc.
  7. Low socioeconomic status, parental consanguinity and separation or death and children whose parents were unwilling to participate in the study.


Subjects who had any of the above cases were excluded.

Schizophrenia, different types of ADHD, post-traumatic stress disorder (PTSD), panic attacks, MDD, ASD, Tourette's disorder and BD were defined according to the Diagnostic and Statistical Manual of Mental Disorders V (DSM V) criteria as a history of each. MR was defined as an intelligence quotient (IQ) of 70 or less; epilepsy was defined as a history of recurrent seizures for which no cause can be identified in clinical studies; and chronic drug use was defined as a history of at least one year of continuous use of one or more types of medications. History of moderate to severe head trauma was defined as a trauma that causes the Glasgow coma scale (GCS) <12 and symptoms such as dizziness or persistent confusion, behavioral changes, loss of consciousness, neurological symptoms or coma. Moreover, low socioeconomic status was considered as family income <1000 euro in a month (for a family of three to five members) and parental education lower than diploma.

ADHD was defined according to the DSM-V criteria in those with disease symptoms for at least six months continuously and in two separate environments (both at home and at school) without any organic causes, and it was diagnosed by the Conner's Parent Rating Scale - 48 (CPRS-48).

Abdekhodaie et al reported the sensitivity and specificity of this form of the Conner Questionnaire for the diagnosis of children with ADHD at 90.3% and 81.2%, respectively. [1] It should be mentioned that ADHD diagnosis for children with this disorder was only confirmed after excluding its differential diagnoses, such as hyperthyroidism and lead poisoning.

After the CPRS-48 was completed by the parents, the children were identified with any form of ADHD and were referred to an expert psychiatrist as the project administrator in order to confirm ADHD diagnosis by clinical interview and based on the DSM-V diagnostic criteria.

The collected data were analyzed with SPSS software (Statistical Package for the Social Sciences, version 18.0; SPSS Inc., Chicago, IL, USA) and descriptive statistics methods for frequency determination. Moreover, the Binomial test was used for data analysis. P-values <0.05 were considered to be significant. This study was approved by the ethics committee of the Arak University of Medical Sciences and, in all stages of this study, we adhered to the Helsinki declaration principles and a written consent was obtained from all of the participants prior to the start of the study. Participants were free to exit the study at any time at their will.


   Results Top


The mean age of the children in the case and control groups was calculated at 8.71 ± 9.56 and 9.31 ± 3.32, respectively (P = 0.28). There were 42 boys and 23 girls in the case group and 29 boys and 36 girls in the control group (P = 0.23).

Overall, of the 130 children under study in both groups, nine, 15 and 18 children were affected by ADHD inattentive type, ADHD hyperactive-impulsive type and ADHD mixed type, respectively [Table 1].
Table 1: Frequency (percentage) of the kind of ADHD based on the group.

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Between the prevalence of ADHD inattentive type (P = 0.862), ADHD hyperactive-impulsive type (P = 0.228) and ADHD mixed type (P = 0.361), there were no significant difference between the groups.

The results showed that there is no significant relationship between ADHD inattentive type (P = 0.07), ADHD hyperactive-impulsive type (P = 0.31) and ADHD mixed type (P >0.05) and gender distribution of the children under study in both groups.


   Discussion Top


Our study showed that there is no significant relationship between the disorders, including ADHD inattentive type, ADHD hyperactive- impulsive type and ADHD mixed type - and SDNS in the affected children and the prevalence of ADHD in the children with SDNS does not exceed the control group. Neuhaus et al found that behavior and psychosocial adjustment are impaired in children with steroid-sensitive nephrotic syndrome (SSNS). [4]

Mehta et al reported that the presence of minor behavior problems in a significant proportion of children with NS and the severity of these problems may be related to the attitude of the mother toward the child's illness. [6] Guha et al reported that prevalence of behavior disturbance in children with nephrotic syndrome was significantly higher than that in the healthy children. [7] Hall et al found that children with nephrotic syndrome treated with high-dose oral steroids are at risk of developing clinically relevant behavioral changes. [8] Manti et al found that psycho-social factors and outcomes may be important correlates of children's NS and potential targets of thorough assessment and treatment. [9] Soliday et al reported that children with SSNS often experience serious problems with anxiety, depression and increased aggression during high-dose prednisone therapy for relapse. [10] Ghobrial et al found that emotional symptoms, conduct problems, peer relationship problems, hyperactivity and the overall poor behavior scores might be more likely to be seen in children with SRNS than other NS treatment status, and recommended that attention to behavioral problems of children with NS should be given early during the course of the disease. [3]

To the best of our knowledge, as yet no study has been conducted on the relationship between ADHD and SDNS in children. However, different studies have been conducted on other psychiatric disorders in children with various type of NS. In 2015, Yousefichaijan et al showed that there were no differences between prevalence of ADHD in children with functional constipation and the control group. [11] Also, no differences were found between the prevalence of ADHD in children with early stages of chronic kidney disease (CKD) and the control group. [12] Although in another study, the inattentive type of ADHD in children with primary monosymptomatic nocturnal enuresis (PMNE) was significantly more common than that in healthy children. [13] Yousefichaijan et al stated that overactive bladder in children with ADHD is significantly more common than that in healthy children (control group). [14] Also, the inattentive type and hyperactive-impulsive type of ADHD are more prevalent in children with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis. [15] Therefore, screening for ADHD is necessary in these patients.

A major limitation of our study was the noncooperation of some parents to fill in the ADHD questionnaire and the psychiatric examination of the child. We attempted to minimize this limitation by encouraging the parents to fill in the said questionnaire by explaining the possible usefulness of the study.

Finally, according to similar studies on this subject, it seems that the prevalence of different kinds of psychiatric disorders such as depression, ADs and adjustment disorder in children with the final stage of CKD or ESRD who need dialysis is considerably higher than that in children with the preliminary stages of CKD. However, due to the importance of relationships between different types of psychiatric disorders and CKD [9],[10],[16],[17] and the lack of enough evidence concerning the relationship between ADHD and different levels of CKD in children, conducting further studies in this field is recommended.

Based on the current study, there were no significant differences between prevalence of ADHD in children with SDNS and the control group. Although we expect to see less hyperactivity in the control group, the results showed no difference between the two groups. Because of the importance of the relationships between different types of psychiatric disorders and NS, and the lack of enough evidence concerning the relationship between ADHD and different stages of NS in children, conducting further studies in this field is recommended.

Conflict of Interest

The authors declared no potential conflict of interests with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

 
   References Top

1.
Abdekhodaie Z, Tabatabaei SM, Gholizadeh M. The investigation of ADHD prevalence in kindergarten children in northeast Iran and a determination of the criterion validity of Conners' questionnaire via clinical interview. Res Dev Disabil 2012;33:357-61.  Back to cited text no. 1
    
2.
Yousefichaijan P, Salehi B, Firouzifar MR, Sheikholeslami H. The correlation between ADHD and enuresis in children with nocturnal enuresis. J Isfahan Med Sch 2012;30:1-9.  Back to cited text no. 2
    
3.
Ghobrial EE, Fahmey SS, Ahmed ME, Botrous O. Behavioral changes in Egyptian children with nephrotic syndrome. Iran J Kidney Dis 2013;7:108-16.  Back to cited text no. 3
    
4.
Neuhaus TJ, Langlois V, Licht C. Behavioural abnormalities in children with nephrotic syndrome - an underappreciated complication of a standard treatment? Nephrol Dial Transplant 2010;25:2397-9.  Back to cited text no. 4
[PUBMED]    
5.
Soliday E, Grey S, Lande MB. Behavioral effects of corticosteroids in steroid-sensitive nephrotic syndrome. Pediatrics 1999;104:e51.  Back to cited text no. 5
    
6.
Mehta M, Bagga A, Pande P, Bajaj G, Srivastava RN. Behavior problems in nephrotic syndrome. Indian Pediatr 1995;32:1281-6.  Back to cited text no. 6
    
7.
Guha P, De A, Ghosal M. Behavior profile of children with nephrotic syndrome. Indian J Psychiatry 2009;51:122-6.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.
Hall AS, Thorley G, Houtman PN. The effects of corticosteroids on behavior in children with nephrotic syndrome. Pediatr Nephrol 2003;18:1220-3.  Back to cited text no. 8
    
9.
Manti P, Giannakopoulos G, Giouroukou E, et al. Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables. Biopsychosoc Med 2013;7:10.  Back to cited text no. 9
    
10.
Soliday E, Kool E, Lande MB. Psychosocial adjustment in children with kidney disease. J Pediatr Psychol 2000;25:93-103.  Back to cited text no. 10
    
11.
Yousefichaijan P, Salehi B, Shekholeslami H, et al. Is attention deficit hyperactivity disorder more prevalent in children with functional constipation. Sch J Appl Med Sci 2015;3:209-13.  Back to cited text no. 11
    
12.
Yousefichaijan P, Sharafkhah M, Salehi B, Rafiei M. Attention deficit hyperactivity disorder in children with early stages of chronic kidney disease. Med J Islam Repub Iran 2015;29:181.  Back to cited text no. 12
    
13.
Yousefichaijan P, Sharafkhah M, Rafeie M, Salehi B. Attention deficit hyperactivity disorder in children with primary monosymptomatic nocturnal enuresis: A case-control study. Pediatr Nephrol;2015;30:1587-8.  Back to cited text no. 13
    
14.
Yousefichaijan P, Salehi B, Sharafkhah M, Rafeie M. Psychiatric disorders and lower urinary tract symptoms (LUTS): Is attentiondeficit/hyperactivity disorder more prevalent in children with overactive bladder? Pediatr Nephrol 2015;30:1587.  Back to cited text no. 14
    
15.
Yousefichaijan P, Sharafkhah M, Vazirian S, et al. Attention-deficit/hyperactivity disorder in children undergoing peritoneal dialysis. Nephrourol Mon 2015;7:e24427.  Back to cited text no. 15
    
16.
Bender BG, Lerner JA, Poland JE. Association between corticosteroids and psychologic change in hospitalized asthmatic children. Ann Allergy 1991;66:414-9.  Back to cited text no. 16
    
17.
Soliday E, Kool E, Lande MB. Family environment, child behavior, and medical indicators in children with kidney disease. Child Psychiatry Hum Dev 2001;31:279-95.  Back to cited text no. 17
    

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Correspondence Address:
Mahdyieh Naziri
Department of Basic Sciences, Arak University of Medical Sciences, Arak
Iran
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DOI: 10.4103/1319-2442.168624

PMID: 26586060

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