childhood nephrotic syndrome ( ns ) is the commonest glomerular lesion encountered in childhood [ 1 , 2 ] . although various histological features have been described , the most important determinant of outcome of this condition is steroid responsiveness which is , however , not uniformly distributed globally
. high steroid responsiveness has traditionally been demonstrated in temperate regions of the world and , conversely , high steroid resistance in tropical regions of the world like nigeria [ 310 ] .
consequently , the black race is often considered an indication for kidney biopsy in children with ns .
recent reports however suggest changes in steroid responsiveness of nephrotic syndrome , with steroid resistance being increasingly reported in non - blacks while some regions have experienced increasing steroid sensitivity [ 1115 ] .
previous reports from nigeria demonstrated high steroid resistance ranging between 35% and 92% [ 69 , 1518 ] .
cursory observations of the cohort of children receiving care in our centre suggested high steroid sensitivity , hence the need for this report .
this study therefore evaluates the pattern of steroid sensitivity among a cohort of black children with childhood nephrotic syndrome .
the study was conducted at the paediatric nephrology unit of the lagos university teaching hospital , a 760-bed tertiary hospital in southwest nigeria .
the hospital is one of the two referral centres in the state providing renal care to children in lagos state and its environs .
the records of all children managed for nephrotic syndrome between january 2008 and april 2013 were reviewed .
nephrotic syndrome was diagnosed based on the following : 24-hour urine protein > 40  mg / m / hr or spot urine protein : creatinine ratio > 200  mg / mmol , hypoalbuminemia ( serum albumin < 25 
g / l ) , generalized oedema , and hypercholesterolemia ( serum cholesterol > 5.2 
the following results were retrieved : blood pressure , urine microscopy and culture , serum electrolytes , calcium , phosphate , urea and creatinine , blood film for malaria parasite , haemoglobin genotype , renal ultrasound scan and screening for hepatitis b , hepatitis c , and human immunodeficiency virus , antinuclear antibodies , anca , and complement levels .
microscopic haematuria was defined as > 5 red blood cells ( rbcs ) per high field of a centrifuged urine specimen and glomerular filtration rate ( egfr ) was estimated using the modified schwartz formula .
chronic disease was defined according to the kidney disease outcomes qualitative initiative ( kdoqi ) guidelines .
hypertension was defined as blood pressure > 95th centile for age , gender , and height on three consecutive occasions .
urinary tract infection was diagnosed in the presence of supportive urinalysis findings and significant growth of uropathogenic organism in an appropriately collected urine specimen .
systemic lupus erythematosus ( sle ) was diagnosed using the revised american college of rheumatology criteria .
socioeconomic classification was done using the classification by oyedeji   which employs the educational status and occupation of parents .
at first presentation , patients receive oral prednisolone at 60  mg / m daily for 46 weeks .
since 2012 , following kdigo ( kidney disease improving global outcomes ) recommendations , we have extended treatment to 8 weeks to define steroid resistance .
following remission , the dose is reduced to 40  mg / m on alternate days for 4 weeks and gradually tapered over 35 months . steroid dependence ( sd )
was treated with the addition of levamisole ( 2.5  mg / kg / day ) on alternate days or cyclophosphamide ( oral or intravenous ) .
steroid resistance was treated with oral ( 2  mg / kg / day for 8weeks ) or intravenous ( 500  mg / m / month for 6 months ) cyclophosphamide , angiotensin converting enzyme ( ace ) inhibitors , or cyclosporine . since 2012 ,
cyclosporine rather than cyclophosphamide has become the preferred drug for the management of steroid resistance .
renal biopsies were performed by the paediatric nephrologists for steroid resistant or secondary cases of ns .
terms are defined as follows : remission : nil or trace proteinuria < 30  mg / dl for 3 consecutive days after commencing treatment ; steroid resistant nephrotic syndrome ( srns ) : failure to achieve remission after 68 weeks of daily prednisolone ; relapse : recurrence of 100  mg / dl ( 2 + ) proteinuria for 3 consecutive days after having been in remission ; steroid dependent nephrotic syndrome ( sdns ) : two consecutive relapses during alternate day steroid therapy or within 14 days after cessation of steroids ; frequently relapsing nephrotic syndrome ( frns ) : two or more relapses within 6 months of initial response or 4 relapses in any 12-month period .
continuous data were represented as mean or median while categorical data were presented as percentages .
significance between steroid sensitivity and some variables was determined using chi - square test while comparison of means was done with student 's t - test
we managed 108 children , 68 males and 40 females ( m  :  f = 1.7  :  1 ) . age range was 8 months to 15.4 years ( median 5.9 years ) .
their age distribution is shown in figure 1 , reflecting a bimodal distribution with a peak at 1 to 2 years and a slightly lesser one at about 9 - 10 years .
of 88 children with complete data on socioeconomic status , majority , 38 ( 45.2% ) , were from the lower socioeconomic class while 31 ( 36.9% ) and 15 ( 17.9% ) were from the middle and upper socioeconomic classes , respectively .
g / l  0.82 with mean serum cholesterol of 10.4  4.4  mmol / l .
most of the children , 94 ( 87% ) , had normal creatinine levels at presentation .
haematuria was present in ( 48 ) 44% , hypertension in ( 46 ) 43% , while ( 27 ) 25% had urinary tract infection .
a secondary cause was found in 10 children as follows : systemic lupus erythematosus ( 3 ) , sickle cell disease ( 3 ) , chronic glomerulonephritis ( 2 ) , infantile ns ( 1 ) and down 's syndrome with cyanotic glomerulopathy ( 1 ) .
five died before steroid sensitivity could be determined while others were unavailable due to loss to follow - up .
steroid sensitivity among children with ins was 82.8% ( 72/87 ) but 75.9% ( 72/95 ) overall .
twelve ( 16.7% ) of those with ssns were either steroid dependent or frequently relapsing , and 23 children ( 24.2% ) were steroid resistant .
time to remission in steroid sensitive patients ranged from 3 to 38 days ( median 7 days ) .
fifteen children were biopsied : 14 with srns of whom 8 had idiopathic srns and an 11-year - old male at presentation on account of age , macroscopic haematuria , and hypertension .
biopsy was not done in the others due to refusal to consent , transfer to another facility , or death .
histological findings were as follows : focal segmental glomerulosclerosis ( fsgs ) in 8 ( 53.3% ) , minimal change disease ( mcns ) in 3 ( 20% ) and 1 ( 6.7% ) each of membranous nephropathy , membranoproliferative glomerulonephritis ( mpgn ) , diffuse proliferative glomerulonephritis , and class 3 lupus nephritis .
histologic patterns among the 8 with idiopathic srns were fsgs in 5 ( 62.5% ) , mcns in 2 ( 25% ) , and mpgn in 1 ( 12.5% ) . 

lower serum albumin , higher serum cholesterol , older age , haematuria , and raised serum creatinine were all associated with steroid resistance .
seven children ( 6.5% ) , all with srns , developed chronic kidney disease ( ckd ) of whom 5 progressed to end - stage kidney disease ( eskd ) during the review period .
one was with haemoglobin ss disease ( hbss ) presented in ckd while the others ( sle : 2 ; fsgs : 2 ; idiopathic : 2 ) developed ckd within 2 years of diagnosis . there were 7 deaths as follows : complications of eskd in 3 ( lupus nephritis : 1 , fsgs :  1 , and ins :  1 ) ; aki in 2 patients , one of whom had lupus nephritis , and 2 newly diagnosed patients with undetermined steroid sensitivity one of whom died from a cerebrovascular accident .
our study revealed high prevalence of steroid sensitivity among a cohort of black children with ns . in summary
about 76% of the whole cohort and approximately 83% of the cohort with idiopathic childhood nephrotic syndrome achieved remission following treatment with steroids .
the high proportion of steroid sensitivity in this study is remarkable because such high sensitivity has rarely been described in a large sample of black children and ranks similar to that described among children of other races [ 24 ] .
various studies describe ns in children of african descent as being predominantly steroid resistant and nonminimal change on histology . in nigeria ,
steroid resistance ranges between 35% and 92% among different geographical locations [ 69 , 1517 ] table 2 , higher than the 23% in the current study .
doe et al . in ghana   reported steroid resistance of 50% amongst their cohort while bhimma 's group in south africa   reported about 86% steroid resistance among black children . in the latter study ,
steroid sensitivity among indian children in the same cohort was over 65% again highlighting racial differences in steroid sensitivity .
this has led to the recommendation of a kidney biopsy as part of the initial evaluation of black children with ns .
the reasons for this striking observation of high steroid sensitivity likely include the younger age structure of our cohort .
the statistically significant lower median age of the steroid sensitive compared with steroid resistant patients supports this .
a small study from southern nigeria   that reported 80% steroid sensitivity had a young population with a mean age of 5.8 years .
asinobi 's group   also from nigeria reported higher steroid sensitivity but their cohort comprised only children aged  5 years .
this age pattern is similar to that reported among caucasians and asian children where high steroid sensitivity has been reported [ 14 ] .
for instance , in a report from the united kingdom , median age of children with ssns was 4.5 years compared with 6 years in those with srns .
we therefore argue that age and race should be considered together as strong predictors of response to steroid rather than the sole reliance on race .
another plausible explanation for the increased sensitivity observed in our cohort is the absence of certain previously prominent secondary aetiologies of ns in our environment resulting in a relatively higher idiopathic pool , the majority of whom were steroid sensitive .
this is a likely consequence of intensified efforts by the government to reduce the burden of some childhood conditions in the region .
for instance , we did not diagnose any case of quartan malaria nephropathy ( qmn ) , which was previously reported to be a leading cause of steroid resistant nephrotic syndrome in our environment .
previous nigerian authors [ 8 , 27 ] have similarly alluded to the reduced incidence of qmn in the region .
malaria control programs have resulted in improved access to antimalarial drugs over the last two decades and this is likely to have contributed to the decline in associated nephropathy .
doe 's group in ghana   also found no evidence of a tropical form of nephrotic syndrome in their patients . in the same vein , in contrast with reports from south africa   and ghana
, we did not diagnose infections such as hepatitis and schistosomiasis , which we attribute to improved vaccination rates and access to portable water , respectively .
these diseases have seemingly been replaced by others like sle and sickle cell anaemia , as also observed by olowu et al . .
recent availability of diagnostic facilities for the former and improved survival beyond early childhood for the latter could account for this observation .
contrariwise , on the global scene , the incidence of steroid resistant ns in various parts of the world such as the usa [ 11 , 28 ] , poland , india , and canada   is reportedly on increase which has been linked to increasing fsgs among these populations .
although kim 's group   and bonilla - felix et al .   attributed their findings to the large proportion of the african - africans in their cohort , similar observations in homogenous or near homogenous caucasian populations [ 12 , 28 ] suggest the role of other factors .
socioeconomic class is thought to play a role in ns although the exact associations are not very clear .
the majority of our patients were from the lower socioeconomic class similar to a report from india   where 84% of study participants were from the lower socioeconomic class .
while this may suggest a role for infections which are more prevalent in this socioeconomic class of children , we did not find a high prevalence of infection associated ns in this study .
we however also reported a significant proportion of children from the middle socioeconomic class suggesting the role of other factors which are not apparent from this study .
the aetiology of ins remains of continued research interest globally with extensive research into genetic mechanisms howbeit largely in the developed world .
fsgs was also our predominant histologic finding , a finding consistent with other african studies [ 16 , 24 , 25 ] , especially since the era when kidney biopsy was reserved commonly for those with clinical and treatment features not in keeping with minimal change disease .
since minimal change ns is predominantly steroid sensitive , it is safe to assume that if all the children in the present study were to undergo kidney biopsies , it would have been the most predominant histological pattern .
higher cholesterol levels , hypertension , and haematuria were associated with increased steroid resistance , consistent with published data .
our findings also support the reportedly high frequency of uti in ns , particularly srns , and emphasize the need for screening for this infection in affected children .
as expected , progression to ckd and mortality were predominantly a function of with steroid resistance [ 1 , 4 , 7 ] ; hence , our lower overall mortality of 6.5% , compared with 6.614.3% in other african reports [ 7 , 16 , 24 ] , is not surprising .
mortality was particularly high among those with steroid resistant nephrotic syndrome who progressed to eskd .
this is largely a consequence of a combination of factors which include high cost of care , inadequate facilities for long - term dialysis , and lack of transplant facilities .
late presentation , hence advanced disease in two patients one of whom presented with a cerebrovascular accident , also contributed to the high mortality reported . in conclusion ,
although its retrospective nature resulted in incomplete data in some cases , this was compensated for by its large sample size .
this study and few others in the region [ 14 , 15 ] suggest a changing pattern of steroid sensitivity of childhood ns which may reflect an adaptation to the changing epidemiology of some childhood diseases as alluded to by previous authors .
surveillance of the epidemiology of childhood ns and corresponding modifications in practice guidelines over time are therefore recommended .
 recent reports from both caucasian and black populations suggest changes in steroid responsiveness of childhood nephrotic syndrome . 
 this study was therefore undertaken to determine the features and steroid sensitivity pattern of a cohort of black children with nephrotic syndrome . 
 records of children managed for nephrotic syndrome from january 2008 to april 2013 were reviewed . 
 details including age , response to treatment , and renal histology were analysed . 
 there were 108 children ( median age : 5.9 years , peak : 1 - 2 years ) , 90.2% of whom had idiopathic nephrotic syndrome . 
 steroid sensitivity was 82.8% among children with idiopathic nephrotic syndrome but 75.9% overall . 
 median time to remission was 7 days . 
 median age was significantly lower in steroid sensitive compared with resistant patients . 
 the predominant histologic finding in resistant cases was focal segmental glomerulosclerosis ( 53.3% ) . 
 no cases of quartan malaria nephropathy or hepatitis b virus nephropathy were diagnosed . 
 overall mortality was 6.5% . in conclusion , 
 unusually high steroid sensitivity is reported among a cohort of black children . 
 this is likely attributable to the lower age structure of our cohort as well as possible changing epidemiology of some other childhood diseases . 
 surveillance of the epidemiology of childhood nephrotic syndrome and corresponding modifications in practice are therefore recommended . 