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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 1  |  Page : 67-72
The predictive factors for relapses in children with steroid-sensitive nephrotic syndrome


1 Department of Pediatrics, College of Medicine, Al-Nahrain University, Baghdad, Iraq
2 Al-Kadhymia Teaching Hospital, Baghdad, Iraq

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Date of Web Publication15-Jan-2016
 

   Abstract 

Most patients with steroid-sensitive nephrotic syndrome (SSNS) have frequent relapses (FR); this is considered one of the main problems because of its association with a high incidence of complications. The aim of our study was to evaluate the different factors that might be associated with the occurrence of relapse in SSNS. This is a retrospective study of 80 patients with SSNS conducted at the Pediatric Nephrology Clinic in the Al-Kadhymia Teaching Hospital between January 2011 and November 2011. The study patients were divided into two groups: FR and infrequent relapses (IFR). The age of the study patients was between one and 14 years; 45 patients had FR (56.3%) and 35 patients had IFR (43.7%). Males constituted 55 patients (68.7%) and 25 patients were female (31.3%). The incidence of FR was high in all age-groups, except in the 1-5 years age-group, and was higher in children living in urban areas. There was no significant difference between the two groups in age, gender, place of residence and renal functions. However, there was a significant difference in the presence of hematuria, time taken to respond to therapy and duration of steroid therapy required; all were higher in the FR group. Our results will help clinicians in identifying possible FR such that they may be monitored closely.

How to cite this article:
Ali SH, Ali AM, Najim AH. The predictive factors for relapses in children with steroid-sensitive nephrotic syndrome. Saudi J Kidney Dis Transpl 2016;27:67-72

How to cite this URL:
Ali SH, Ali AM, Najim AH. The predictive factors for relapses in children with steroid-sensitive nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Nov 12];27:67-72. Available from: http://www.sjkdt.org/text.asp?2016/27/1/67/174075

   Introduction Top


Nephrotic syndrome (NS) is primarily a pediatric disorder and is 15-times more common in children than in adults. The reported incidence of NS is 2-3/100,000 children per year. [1] It is characterized by heavy proteinuria (>3.5 g/24-h in adult, 40 mg/m 2 /h in children), hypoalbuminemia <2.5 g/dL, edema and hyperlipidemia. [1],[2],[3] NS is classified into the following: congenital NS, idiopathic NS and secondary NS. [2],[4],[5]

The majority of affected children have steroid-sensitive minimal change disease (MCD). [2],[3] Renal biopsy is recommended for those patients who do not respond to steroids. [3],[6] The majority of children with NS relapse within the first six months of initial therapy. Approximately 30% of children experience only one attack and get cured after a single course of steroids. The peak age of onset of NS is between 18 months and six years and the male to female ratio is 2:1. [7]


   Aim of the study Top


This study was conducted to determine the fre-quency of relapses in children with steroidsensitive NS (SSNS), and included demographic factors such as age, gender and place of residence as predictive factors of occurrence of relapses in SSNS. We also aimed to study the relationship between the presence of hematuria and renal function at initial presentation with occurrence of relapses in SSNS as well as to study the relationship between the time taken to respond to steroid therapy and the duration of steroid therapy of the initial attack and occurrence of subsequent relapses in SSNS.


   Patients and Methods Top


This is a retrospective study of 80 patients with SSNS with an age-range of one to 14 years who were diagnosed, treated and followed-up for at least one year in the Pediatric Nephrology Clinic of the Al-Kadhymia Teaching Hospital. The study was conducted from January to November 2011.

Diagnosis of NS was made according to the following criteria: heavy proteinuria >40 mg/h/m 2 (for older children with collected 24h urine); or protein/creatinine ratio >0.2 g/mmol, Albustix ≥+++ (for non-toilet-trained children or difficult collection of 24-h urine), hypo-albuminemia <2.5 g/dL or edema and hyper-lipidemia with total cholesterol of 170- 200 mg/dL. [1],[2],[3]

Steroid-responsive NS was defined as patients achieving complete remission with steroid therapy for four weeks. [1],[2],[3] Steroid-resistant NS was defined as failure to achieve remission following four weeks of treatment with prednisone 60 mg/m 2 . [1],[2],[3] Hematuria was defined as the presence of at least five red blood cells per microliter of urine. [1],[2],[3]

Reference values for normal blood urea was 40 mg/dL and for serum creatinine were 0.3-0.7 mg/dL for children and 0.5-1 mg/dL for adolescents. [1],[2],[3]

Treatment at the Pediatric Nephrology Unit was according to the protocol of the International Society for Kidney Disease in Children (ISKDC). [1],[2],[3] For the initial attack, the treatment protocol consisted of prednisone 60 mg/m 2 / day in divided doses for four weeks followed by 40 mg/m 2 /day in divided doses. This was followed by alternate-day therapy for four more weeks, which was tapered thereafter.

Relapse was treated with prednisone in a dose of 60 mg/m 2 /day, which was continued for three days after the urine became proteinfree, followed by alternate-day prednisone 40 mg/m 2 for four weeks.

The following data were taken from the record files of the patients: age at presentation, gender, place of residence, hematuria at initial presentation, renal function (B. urea, S. creatinine), time needed to respond to steroid therapy, duration of steroid therapy and number of relapses.

The exclusion criteria included patients with incomplete data at initial presentation, those who were followed-up for <12 months and those who had steroid-resistant NS and those with congenital NS.

Accordingly, the study patients were divided into two groups: [1],[2],[3]

  1. Infrequent relapses (IFR): less than two relapses within six months of the initial response or less than four relapses for any year thereafter.
  2. Frequent relapses (FR): two or more relapses within six months of initial response or four or more relapses within a period of one year.


The data were analyzed by comparing patients with FR and IFR regarding age and sex, place of residence, presence of hematuria, renal function (B. urea and S. creatinine), time needed to respond to steroid therapy and duration of maintenance steroid therapy.

No Institutional Ethics Committee clearance was sought because the work performed was the usual investigations and treatment.


   Statistical analysis Top


Data collected were analyzed using available statistical software package, SPSS version 10:00. The data are presented as simple measures of number or percentage using the Chisquare test. For testing the statistical significance of difference between the different parameters, the number and percentage with use of probability value are presented. P-value <0.05 was considered significant.


   Results Top


A total of 80 children with SSNS were included in this study. Of them, 45 patients had FR (56.3%) and 35 patients had IFR (43.7%). Males constituted 55 of all patients (68.7%) and 25 patients were female (31.3%); the male to female ratio was 2.2:1.

The most common age-group at presentation was 1-5 years, comprising a total of 51 patients (63.7%).

The duration of follow-up ranged from 12 to 72 months, with a mean of 24.7 ± 13.79 months (SD).

The two groups were compared with relation to the following:

Gender

The incidence of FR was higher in females compared with males; the difference was not statistically significant (P-value = 0.104; [Table 1]).
Table 1: Correlation of relapses in children with nephrotic syndrome by gender, age and place of residence.

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Age

The incidence of FR was high in all agegroups, except in the 1-5 years age-group; there were 24 IFR (68.6%) and 27 FR (60%) in this age-group and the difference was not statistically significant (P-value = 0.708; [Table 1]).

Place of residence

FR were more common in children living in urban regions (n = 24, 53.3%) than in those living in rural regions (n = 21, 46.7%); however, there was no statistically significant difference (P-value = 0.734; [Table 1]).

Hematuria

A total of 15 patients presented with hematuria; 13 of them had FR (28.9%) while two had IFR (5.7%). The difference was statistically significant (P-value = 0.008; [Table 2]).
Table 2: Correlation of relapse in patients with nephrotic syndrome with the presence of hematuria at onset.

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Time needed to respond to steroid therapy

Majority of patients with IFR (n = 33, 94.3%) responded to steroid therapy in <2 weeks, while most patients with FR (n = 23, 51.1%) showed response to steroids within two to four weeks. A statistically significant difference was found, with a P-value of 0.001 [Table 3].
Table 3: Correlation of relapses in patients with nephrotic syndrome with time needed to respond to steroid therapy and duration of maintenance steroid therapy.

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Duration of maintenance steroid therapy

More patients with IFR (n = 15, 42.9%) were treated with a longer duration of steroid therapy for three to six months, while patients with FR (n = 12, 26.7%) required treatment for shorter periods of time [Table 3].

Renal function test

Majority of patients in both the IFR and the FR group recorded normal values of renal function parameters and there was no statistically significant difference between the two groups as shown in [Table 4].
Table 4: Correlation of relapses in patients with nephrotic syndrome with renal function: blood urea and serum creatinine.

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   Discussion Top


This study showed a predominance of male patients over females, and the result was similar to studies elsewhere. [2],[7],[8],[9],[10],[11],[12],[13] The most common age-group at presentation was 1-5 years, which was also noticed in previous studies from different regions. [10],[11],[12],[13],[14]

In our study, 56.3% of patients had FR, which is higher than the prevalence of IFR (43.7%); similar findings have been reported by Esfahani et al, [7] Anderson et al, [13] Constantinescu et al [15] and Béatrice et al. [16]

In agreement with previous studies performed by Constantinescu et al, [15] Shuichiro et al [17] and Takeda et al, [18] we did not find any correlation between age at presentation and future relapses among patients with NS. On the other hand, Anderson et al, [13] and Sarker et al [19] found a significant correlation between age at presentation <4 years and <5 years, respectively, and an increased incidence of relapses in the future.

A recent study from India found that patients with FR were younger at onset of the disease, and the frequency of relapses declined with increasing age. [20] This discrepancy may be related to the racial differences in the study population of different studies as well as the different patterns of idiopathic NS in the various ethnic groups. [13]

Several studies have reported a negative correlation between gender and FR. [15],[17],[18],[19],[20] Anderson et al [13] reported that male gender was associated with a higher risk of steroid dependency and FR despite the prolongation of the steroid course. Another study found that male gender is a predictive factor for FR. [21]

In our study, FR were more common among patients living in urban than in rural regions. This finding is in contrast to Sarker et al, who reported a significantly higher incidence of FR in rural children than in urban children (P <0.05). [19] Their explanation for this observation was the delay in the initiation of specific treatment in rural areas.

An interesting finding in this study was the relationship between the presence of hematuria at initial presentation and future relapse. This association was highlighted by several studies. [15],[19],[21] Jei-wen et al [22] reported a prevalence of hematuria at initial presentation of 28% in a group of 50 children with NS aged >8 years. A recent Indian study recorded that the presence of hematuria was independently associated with late steroid resistance. [20]

Another interesting finding in this study was a statistically significant association between early response to steroid therapy and increased incidence of IFR in patients with SSNS. Shuichiro et al reported that patients who responded within eight days of initial steroid therapy showed a favorable clinical course, while those with a delayed response (9 or more days) had a steroid-dependent course. [17]

This finding was highlighted by Yap et al, who reported that initial duration of remission of nine days or longer was significantly associated with steroid dependency in 91 Asian children with SSNS. [23] Also, Constantinescu et al recorded that there was a tendency for patients who took a longer time to respond to be FR or were steroid dependent. However, this was significant only among patients without hematuria, because those with hematuria had similar chances of being IFR or FR/steroid dependency. [15]

Two previous studies performed by Constantinescu et al [15] and Trompeter et al [24] reported less-frequent relapses among their studied patients in relation to a longer duration of steroid therapy, but these results were statistically not significant; their findings were similar to ours.

On the other hand, Anderson et al. [13] found a significant relationship between prolonged steroid therapy (>12 weeks) and reduction in relapse frequency.

In conclusion, our study suggests that FR was more frequently recorded than IFR among children with SSNS; there was a male predominance and the peak age of occurrence of NS was 1-5 years. There was a significant correlation between early response to steroid therapy and IFR, while the presence of hematuria at initial presentation correlated significantly with FR. These data will help in the early identification of children with FR and thus enable proper care.

 
   References Top

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Vogt BA, Avner ED. Condition particularly associated with proteinuria. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Text Book of Pediatrics. 19th ed., Vol. 527. Philadelphia: Saunders; 2007. p. 2190-5.  Back to cited text no. 2
    
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Niaudet P. Steroid sensitive idiopathic nephrotic syndrome & steroid resistance idiopathic nephrotic syndrome in children. In: Avner ED, Harmon WE, Niaudet P, eds. Pediatric Nephrology. 6th ed., Vol. 27, 28. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 543-67.  Back to cited text no. 3
    
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El-Najjar M. Urinary system. In: Pediatic Clinical Diagnosis. 5th ed., Vol. 9. Egypt: AlAhram Commercial Press, Kalyoub; 2005. p. 314.  Back to cited text no. 4
    
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Watson AR, Tayler CM, Graw MM. Disorders of urinary system. In: Mctntosh N, Helms PJ, Smyth RL, eds. Farfar & Arneil's Text Book of Pediatric. 16th ed., Vol. 16. Philadelphia: Churchill Livingston; 2003. p. 633-4.  Back to cited text no. 5
    
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7.
Esfahani ST, Madani A, Asgharian F, et al. Clinical course and outcome of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2011;26:1089-93.  Back to cited text no. 7
    
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Kabuki N, Okugawa T, Hayakawa H, Tomizawa S, Kasahara T, Uchiyama M. Influence of age at onset on the outcome of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 1998;12:467-70.  Back to cited text no. 8
    
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Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003;362:629-39.  Back to cited text no. 9
    
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Wong W. Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: Results of a threeyear national surveillance study. J Paediatr Child Health 2007;43:337-41.  Back to cited text no. 10
    
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Reshi AR, Bhat MA, Najar MS, et al. Etiological profile of nephrotic syndrome in Kashmir. Indian J Nephrol 2008;18:9-12.  Back to cited text no. 11
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Rüth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ. Children with steroidsensitive nephrotic syndrome come of age: Long-term outcome. J Pediatr 2005;147:202-7.  Back to cited text no. 12
    
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Andersen RF, Thrane N, Noergaard K, Rytter L, Jespersen B, Rittig S. Early age at debut is a predictor of steroid-dependent and frequent relapsing nephrotic syndrome. Pediatr Nephrol 2010;25:1299-304.  Back to cited text no. 13
    
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Anochie I, Eke F, Okpere A. Childhood nephrotic syndrome: Change in pattern and response to steroids. J Natl Med Assoc 2006;98: 1977-81.  Back to cited text no. 14
    
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Constantinescu AR, Shah HB, Foote EF, Weiss LS. Predicting first-year relapses in children with nephrotic syndrome. Pediatrics 2000;105(3 Pt 1):492-5.  Back to cited text no. 15
    
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Letavernier B, Letavernier E, Leroy S, BaudetBonneville V, Bensman A, Ulinski T. Prediction of high-degree steroid dependency in pediatric idiopathic nephrotic syndrome. Pediatr Nephrol 2008;23:2221-6.  Back to cited text no. 16
    
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Fujinaga S, Daishi H, Naoto N. Early identification of steroid dependency in Japanese children with steroid-sensitive nephrotic syndrome undergoing short-term initial steroid therapy. Pediatr Nephrol 2010;25:1299-304.  Back to cited text no. 17
    
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Takeda A, Takimoto H, Mizusawa Y, Simoda M. Prediction of subsequent relapse in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2001;16:888-93.  Back to cited text no. 18
    
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Sarker MN, Islam MM, Saad T, et al. Risk factor for relapse in childhood nephrotic syndrome - A Hospital Based Retrospective Study. Faridpur Med Coll J 2012;7:18-22.  Back to cited text no. 19
    
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Sinha A, Hari P, Sharma PK, et al. Disease course in steroid sensitive nephrotic syndrome. Indian Pediatr 2012;49:881-7.  Back to cited text no. 20
    
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Noer MS. Predictors of relapse in steroidsensitive nephrotic syndrome. Southeast Asian J Trop Med Public Health 2005;36:1313-20.  Back to cited text no. 21
    
22.
Chang JW, Tsai HL, Wang HH, Yang LY. Clinicopathological features and prognosis of Chinese children with idiopathic nephrotic syndrome between different age groups. Eur J Pediatr 2009;168:1189-94.  Back to cited text no. 22
    
23.
Yap HK, Han EJ, Heng CK, Gong WK. Risk factors for steroid dependency in children with idiopathic nephrotic syndrome. Pediatr Nephrol 2001;16:1049-52.  Back to cited text no. 23
    
24.
Abeyagunawardena AS, Hindmarsh P, Trompeter RS. Adrenocortical suppression increases the risk of relapse in nephrotic syndrome. Arch Dis Child 2007;92:585-8.  Back to cited text no. 24
    

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Correspondence Address:
Shatha Hussain Ali
Department of Pediatrics, College of Medicine, Al - Nahrain University, P. O. Box 70074, Baghdad
Iraq
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DOI: 10.4103/1319-2442.174075

PMID: 26787569

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   Patients and Methods
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