usually the course of ns in children is chronic with periods of recurrence and if untreated , it will lead to end - stage renal disease ( esrd ) and death .
now oral corticosteroids are the first line treatment of ns and the majority of these children respond to steroids .
about 12 - 22% of the children with ns are steroid resistant and 70% will experience an episode of relapse .
long - term corticosteroid therapy has several known adverse effects like obesity , diabetes mellitus , poor growth , adrenal suppression , and hypertension . despite the fact that both ns and its therapeutic protocols ( steroids , and steroid sparing agents ) can affect growth , clinical studies have shown conflicting results[35 ] .
this study intends to assess the effect of corticosteroid on linear body growth of children .
the study was conducted in children 's medical center , the largest university affiliated pediatric hospital in tehran . in a hospital - based retrospective approach
the effect of steroid therapy on linear growth of nephrotic children in a 5-year follow up was evaluated .
hospital records of 147 patients with diagnosis of ns within 1988 - 2008 who met the following criteria were reviewed and data extracted ; age within 1 to 15 years , admission to the center on the first episode of ns , steroid therapy for at least four months , minimum follow - up of five years , accurate and careful data registry of height measurements and treatment modalities .
all patients had normal renal function with serum creatinine level of < 0.8 mg / dl and creatinine clearance of 100 ml / min per 1.73 m at the last visit .
nephrotic syndrome was considered in patients who had proteinuria ( > 40 mg / m / h ) , and hypoalbuminemia ( serum albumin < 2.5 g / dl ) according to the criteria of international study of kidney disease in children ( iskdc)[6 , 7 ] .
the  remission of the disease was characterized by disappearance of albuminuria ( dipstick testing 0 to trace ) , whereas  relapse was defined as reappearance of proteinuria ( dipstick testing 2 + for at least 3 consecutive days ) .
kidney biopsy had been done in children with early ( < 1 year old ) or late ( > 10 years ) disease onset , presence of gross hematuria , persistent hypertension with or without microscopic hematuria , low gfr unresponsive to correction of intravascular volume depletion , steroid resistance or dependence , frequent relapses , family history of glomerulopathies , and low c3 level .
patients were initially treated with 60 mg / m / d ( 2 mg / kg / d ) of oral steroids [ prednisolone ( psl ) ] for at least 4 weeks . the therapy was followed by another 4 weeks with 40 mg / m / d ( 1.5 mg / kg / d ) on alternate days and then it was tapered and stopped over the next 8 - 12 weeks .
the above therapeutic protocol had been prescribed for the first episode of the disease , while an individualized treatment had been considered for the next episodes .
steroid - sparing agents ( including levamisole , cyclophosphamide , cyclosporine a , and azathioprine ) had been given if indicated .
the period of psl administration , total dosage of psl in terms of milligram per kilogram , and prescription of steroid - sparing agent treatments were recorded for each patient .
data on subjects height at admission and in the last follow - up visit were gathered . in order to compare their linear growth with normal population and adjustment of age and sex , standard deviation score ( sds ) of the height was calculated by plotting figures on centers for disease control of usa ( cdc ) growth chart for the respective age and sex .
the height sds ( ht 
 sds ) was then calculated for each subject according to the following equation : height sds(htsds)=(patient s height - height at50thpercentile)/(height at50thpercentile - height at5thpercentile ) 
  changes in ht 
 sds ( ht 
 sds ) throughout follow - up visits were also calculated . in order to evaluate the effect of pre - pubertal steroid therapy of ns on patients linear growth , age of 10 years for female and 12 years for male patients
was considered as the age of puberty . analysis used spss version 15 ( spss , inc , chicago , il , usa ) .
chi - square test and student 's t - test were used to compare losses and gains in percentiles with nominal variables such as histological type of ns , sex , and steroid - sparing medications .
the pearson 's correlation was used to compare gains and losses in percentiles ( ht 
 sds ) in the patient population as a whole and in selected subgroups , considering continuous variables including onset age , age at last follow up , duration of psl medication , and cumulative received psl .
the study was conducted in children 's medical center , the largest university affiliated pediatric hospital in tehran . in a hospital - based retrospective approach
the effect of steroid therapy on linear growth of nephrotic children in a 5-year follow up was evaluated .
hospital records of 147 patients with diagnosis of ns within 1988 - 2008 who met the following criteria were reviewed and data extracted ; age within 1 to 15 years , admission to the center on the first episode of ns , steroid therapy for at least four months , minimum follow - up of five years , accurate and careful data registry of height measurements and treatment modalities .
all patients had normal renal function with serum creatinine level of < 0.8 mg / dl and creatinine clearance of 100 ml / min per 1.73 m at the last visit .
nephrotic syndrome was considered in patients who had proteinuria ( > 40 mg / m / h ) , and hypoalbuminemia ( serum albumin < 2.5 g / dl ) according to the criteria of international study of kidney disease in children ( iskdc)[6 , 7 ] .
the  remission of the disease was characterized by disappearance of albuminuria ( dipstick testing 0 to trace ) , whereas  relapse was defined as reappearance of proteinuria ( dipstick testing 2 + for at least 3 consecutive days ) .
kidney biopsy had been done in children with early ( < 1 year old ) or late ( > 10 years ) disease onset , presence of gross hematuria , persistent hypertension with or without microscopic hematuria , low gfr unresponsive to correction of intravascular volume depletion , steroid resistance or dependence , frequent relapses , family history of glomerulopathies , and low c3 level .
patients were initially treated with 60 mg / m / d ( 2 mg / kg / d ) of oral steroids [ prednisolone ( psl ) ] for at least 4 weeks .
the therapy was followed by another 4 weeks with 40 mg / m / d ( 1.5 mg / kg / d ) on alternate days and then it was tapered and stopped over the next 8 - 12 weeks .
the above therapeutic protocol had been prescribed for the first episode of the disease , while an individualized treatment had been considered for the next episodes .
steroid - sparing agents ( including levamisole , cyclophosphamide , cyclosporine a , and azathioprine ) had been given if indicated .
the period of psl administration , total dosage of psl in terms of milligram per kilogram , and prescription of steroid - sparing agent treatments were recorded for each patient .
data on subjects height at admission and in the last follow - up visit were gathered . in order to compare their linear growth with normal population and adjustment of age and sex , standard deviation score ( sds ) of the height was calculated by plotting figures on centers for disease control of usa ( cdc ) growth chart for the respective age and sex . the height sds ( ht 
 sds )
was then calculated for each subject according to the following equation : height sds(htsds)=(patient s height - height at50thpercentile)/(height at50thpercentile - height at5thpercentile ) 
  changes in ht 
 sds ( ht 
 sds ) throughout follow - up visits were also calculated .
in order to evaluate the effect of pre - pubertal steroid therapy of ns on patients linear growth , age of 10 years for female and 12 years for male patients was considered as the age of puberty .
analysis used spss version 15 ( spss , inc , chicago , il , usa ) .
chi - square test and student 's t - test were used to compare losses and gains in percentiles with nominal variables such as histological type of ns , sex , and steroid - sparing medications .
the pearson 's correlation was used to compare gains and losses in percentiles ( ht 
 sds ) in the patient population as a whole and in selected subgroups , considering continuous variables including onset age , age at last follow up , duration of psl medication , and cumulative received psl .
hospital records of 147 patients consisting of 99 ( 67.3% ) males and 48 ( 32.7% ) females were reviewed .
mean age of the subjects at first visit was 5.14 ( range 1 to 15 years ) and the mean follow - up time was 9.3 years ( range 4 to 20 years ) .
ns had a significantly earlier onset in the male patients compared to the female group ( p=0.024 ) . by the last follow - up visit , 6 ( 12.5% ) female patients were 10 years and 42 ( 87.5% ) > 10 years old , while 34 ( 34.35% ) male patients were 12 years and 65(65.7% ) > 12 years old .
percutaneous renal biopsy was performed in 34.7% of the subjects , in 26 of whom histo - pathological findings were compatible with minimal change ns .
mean total dose of prednisolone was 2205.90 mg / kg ( 1265.40 ) with a mean duration of 7.05 years steroid therapy .
steroids were given to 69 subjects before puberty ( 54 males and 15 females ) , while 78 patients ( 45 males and 33 females ) received psl before and after puberty .
one , two , or three ssa were given in conjunction with prednisolone in 88 ( 59.9% ) children ( 53 , 21 , or 14 patients respectively ) .
the mean ht 
 sds of the 147 patients initial height was -0.761.96 , and the final ht 
 sds -0.89 2.05(p=0.49 ) .
the height of 39 ( 21.1% ) patients measured < 5% cdc ( less than 2 sd of normal population ) at the first visit .
however , 13 of these patients had reached the 5 percentile for height or higher ( table 1 ) . 
 
cross - tabulation between htsds of the first and last follow - up visit sds : standard deviation score/ht : gains and losses in percentiles of height ( growth change ) sixty - two children ( group a ) had linear growth improvement during the follow - up time , whereas 85 ( group b ) were found to have growth retardation . those who had improved linear growth included 40 males and 22 females with the mean initial and final ht 
 sds of -1.631.87 and -0.082.13 respectively ( p<0.001 ) .
first height of 22 ( 15.0% ) of these children was below the 5 percentile .
however , by the last follow - up visit , 13 of them had heights above 5 percentile . on the contrary ,
group b comprised 85 ( 59 male and 26 female ) patients , whose average ht 
 sds for initial and final height records were 0.131.78 and 1.591.68 respectively ( table 2 ) . from the first till the last
follow up visit , 22 patients suffered negative growth below the 5 percentile while the rest , though showing negative growth , remained above the 5 percentile . as it is shown in table 3 ,
patients that had received ssa were younger and had received significantly higher doses of psl . 
 
comparison of growth determinants between children according to their growth status , improvement ( group a ) or retardation ( group b ) sds : standard deviation score comparison of growth indicators between patients who used prednisolone alone and those who used additional steroid - sparin ssa : steroid sparing agent/ht : gains and losses in percentiles of height ( growth change ) linear growth was not related to age at onset , age at final follow - up , duration of the disease , or cumulative dosage of psl ( table 4 ) . 
  pearson correlation coefficients and significance ( p. values ) between growth change ( htsds ) and growth determinants we also compared the various histological types of ns for differences in the growth indicators .
significant differences were noticed in the age at onset ( p=0.008 ) , duration ( p=0.006 ) and dose ( p=0.006 ) of steroid therapy , but not the age at the last follow - up visit .
in the past when steroids were not prescribed for ns , a major cause of growth retardation was protein calorie malnutrition secondary to poor appetite , malabsorption due to gi tract edema , and proteinuria .
today , corticosteroids are believed to be the major cause , though emotional deprivation and chronic anxiety may also play a role . in ns ,
the dosage and duration of steroid therapy and renal function are principal factors associated with patients linear growth .
prolonged high - dose corticosteroid administration suppresses growth . however , previous studies on ns raised controversies , whereas some reported loss of growth velocity in long - term steroid therapy[812 ] , others failed to show significant growth impairment[2 , 1317 ] . in the current study , we found no difference between subjects first and final height .
this favorable outcome might be due to long - term maintenance steroid therapy administered on alternate days .
however , inclusion of children with a benign course of ns might also underestimate the side effects of prolonged steroid treatment .
linear growth was not related to gender , age at onset , age at final follow - up , duration of the disease , cumulative dosage of psl , and ns histology .
there was no difference in mean ht 
 sds change between patients treated with and without steroid - sparing agents ( -0.142.30 vs. -0.11 2.13 ; p=0.93 ) , which is in accordance with the findings of the study by matsukura et al , in which they found no association between height sds change and ssa use in ns patients . as previously reported in a study by padilla et al , these agents are beneficial for linear growth through steroid sparing effect . total psl dose and duration of steroid therapy
this is in agreement with an earlier study by kitamura , which showed no significant reduction in the dose or duration of prednisolone treatment by concomitant ssa administration as it is more probable that these patients were steroid resistant .
we also compared various histological types of ns for differences in the potential growth determinants .
age at onset of the disease , as well as duration and dose of steroid therapy were significantly different .
though a larger population of renal biopsy is required to better elucidate these differences , our data is in agreement with those of the iskdc which shows that mcns is more frequent in younger ages[6 , 7 ] .
mcns could , due to its higher relapse rate , more likely cause longer duration and higher cumulative dose of steroid medication .
it is hard to explain the difference between the two groups ( group a and b ) as they were both comparable for potential determinants of ht 
 sds .
even the patients clinical history did not reveal any data suggestive of chronic disease before onset of the ns .
< -2 ( below the 5 percentile ) at first visit , achieved a ht 
 sds of 5 percentile for height by the end of follow up time .
loke et al suggest that catch - up growth compensates for pubertal growth retardation . in subgroup
a , the gain of growth percentiles could possibly be attributed to several factors that acted in isolation or in concert : catch - up growth could have affected 34 of 99 male and 6 of 48 female children who received steroids intermittently and have gained growth percentiles before adolescence in accordance with a study by loke et al . a pubertal growth spurt might have occurred in 45 male and 33 female patients during the follow - up period . both effects ( pubertal growth spurt and catch - up growth ) might have been operating in 20 male and 9 female patients who were able to discontinue steroids before puberty and afterwards , still off steroids , entered puberty during the study period . considering the similarities of group b patients with those of group a , the cause of loss of growth percentiles in group b could be attributed to more sensitivity to side effects of psl or a more severe disease .
corticosteroids are believed to be associated with elevation of serum igf-1 levels that can result in igf resistance and growth retardation . however , this finding is in agreement with several other studies[2225 ] .
this could be due to differences in pharmacokinetics , steroid sensitivity , and severity of the underlying disease .
identifying these factors will be of great value in clinical practice , but until then , steroids side effects have to be monitored individually .
though height sds was not significantly decreased in the studied subjects following prednisolone therapy according to the guidelines of iskdc , mild retardation was observed in a group of children . in order to further elucidate this issue ,
additional research is required with regard to the period of active proteinuria , other causes of growth retardation such as hypothyroidism and vitamin d deficiency as well as accurate consideration of number of relapses .
 objectivesteroids are still the mainstay of management of nephrotic syndrome ( ns ) . 
 it was shown that steroids could impair growth and development of children . however , other clinical studies have shown conflicting results.methodshospital records of 147 children with diagnosis of ns who were followed during 1988 - 2008 are reviewed relating to height measurements . 
 all patients were treated with prednisolone and had been followed for at least five years . 
 height measures were transformed into standard deviation score ( sds ) . 
 information on dose and duration of prednisolone therapy , histological findings of biopsy as well as concomitant use of steroid - sparing agents ( ssa ) were also analyzed.findingsmean age at onset of ns was 5.94 years and at last follow - up visit 15.08 years . 
 all patients had normal renal function during entire duration of the study . 
 analysis of the whole population did not show any significant alterations in the height sds ( htsds ) between the first and the last follow - up visit ( p=0.5 ; 0.762.0 vs. 0.892.05 respectively ) . 
 the patients were divided into two subgroups . subgroup a , which achieved growth improvement , 
 was composed of 62 children ( initial htsds -1.63 ; final htsds -0.08 ; p<0.001 ) and subgroup b , that showed growth retardation , included 85 children ( initial htsds -0.13 ; final htsds -1.59 ; p<0.001).conclusionno statistically significant retardation of linear growth was observed in the study population as a group following treatment with prednisolone according to the guidelines of iskdc . although about 62 subjects had growth retardation , children treated with prednisolone were not different from those who had increased growth . 