journal nepfrotic sindrome

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Research ArticleHigh Steroid Sensitivity among Children with NephroticSyndrome in Southwestern Nigeria

Taiwo Augustina Ladapo,1,2 Christopher Imokhuede Esezobor,1,2 and Foluso Ebun Lesi1,2

Department of Paediatrics, College of Medicine, University of Lagos, PMB , Lagos, Nigeria Department of Paediatrics, Lagos University eaching Hospital, Idi-Araba, PMB , Lagos, Nigeria

Correspondence should be addressed to aiwo Augustina Ladapo; [email protected]

Received February ; Accepted June ; Published July

Academic Editor: ibor Nadasdy

Copyright aiwo Augustina Ladapo et al. Tis is an openaccessarticle distributed underthe CreativeCommons AttributionLicense, whichpermits unrestricted use, distribution, andreproduction in anymedium, providedthe original workis properlycited.

Recent reports rom both Caucasian and black populations suggest changes in steroid responsiveness o childhood nephroticsyndrome. Tis study was thereore undertakento determine the eaturesand steroid sensitivity pattern o a cohort o black childrenwith nephrotic syndrome. Records o children managed or nephrotic syndrome rom January to April were reviewed.Details including age, response to treatment, and renal histology were analysed. Tere were children (median age: . years,peak: - years), .% o whom had idiopathic nephrotic syndrome. Steroid sensitivity was .% among children with idiopathicnephrotic syndrome but.% overall. Median time to remissionwas days. Median age was signicantly lower in steroid sensitivecompared with resistant patients. Te predominant histologic nding in resistant cases was ocal segmental glomerulosclerosis(.%). No cases o quartan malaria nephropathy or hepatitis B virus nephropathy were diagnosed. Overall mortality was .%.In conclusion, unusually high steroid sensitivity is reported among a cohort o black children. Tis is likely attributable to thelower age structure o our cohort as well as possible changing epidemiology o some other childhood diseases. Surveillance o theepidemiology o childhood nephrotic syndrome and corresponding modications in practice are thereore recommended.

1. Introduction

Childhood nephrotic syndrome (NS) is the commonestglomerular lesion encountered in childhood [,]. Although

various histological eatures have been described, the mostimportant determinant o outcome o this condition is steroidresponsiveness which is, however, not uniormly distributed

globally. High steroid responsiveness has traditionally beendemonstrated in temperate regions o the world and, con-

versely, high steroid resistance in tropical regions o the worldlike Nigeria []. Consequently, the black race is ofenconsidered an indication or kidney biopsy in children withNS.

Recent reports however suggest changes in steroidresponsiveness o nephrotic syndrome, with steroid resis-tance being increasingly reported in non-blacks while someregions have experienced increasing steroid sensitivity []. Previous reports rom Nigeria demonstrated high steroidresistance ranging between % and % [,]. Cur-sory observations o the cohort o children receiving care

in our centre suggested high steroid sensitivity, hence theneed or this report. Tis study thereore evaluates the patterno steroid sensitivity among a cohort o black children withchildhood nephrotic syndrome.

2. Materials and Methods

Te study was conducted at the Paediatric Nephrology Unito the Lagos University eaching Hospital, a -bed tertiaryhospital in Southwest Nigeria. Te hospital is one o thetwo reerral centres in the state providing renal care tochildren in Lagos State and its environs. It thereore catersor children across all socioeconomic strata. Te recordso all children managed or nephrotic syndrome betweenJanuary and April were reviewed. Nephroticsyndrome was diagnosed based on the ollowing: -hour

urine protein > mg/m2/hr or spot urine protein: creatinineratio > mg/mmol, hypoalbuminemia (serum albumin< g/L), generalized oedema, and hypercholesterolemia(serum cholesterol>. mmol/L) [,].

Hindawi Publishing CorporationInternational Journal of NephrologyVolume 2014, Article ID 350640, 6 pageshttp://dx.doi.org/10.1155/2014/350640
http://dx.doi.org/10.1155/2014/350640http://dx.doi.org/10.1155/2014/350640


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International Journal o Nephrology

Te ollowing results were retrieved: blood pressure,urine microscopy and culture, serum electrolytes, calcium,phosphate, urea and creatinine, blood lm or malariaparasite, haemoglobin genotype, renal ultrasound scan andscreening or hepatitis B, hepatitis C, and human immun-odeciency virus, antinuclear antibodies, ANCA, and Com-

plement levels. Microscopic haematuria was dened as >red blood cells (RBCs) per high eld o a centriuged urinespecimen and glomerular ltration rate (eGFR) was esti-mated using the modied Schwartz ormula. Chronic diseasewas dened according to the Kidney Disease OutcomesQualitative Initiative (KDOQI) guidelines []. Hypertensionwas dened as blood pressure > th centile or age, gender,and height on three consecutive occasions []. Urinarytract inection was diagnosed in the presence o supportiveurinalysis ndings and signicant growth o uropathogenicorganism in an appropriately collected urine specimen [].Systemic lupus erythematosus (SLE) was diagnosed usingthe revised American College o Rheumatology criteria [].Socioeconomic classication was done using the classica-tion by Oyedeji [] which employs the educational statusand occupation o parents.

3. Treatment Regimen

At rst presentation, patients receive oral prednisolone at mg/m2 daily or weeks. Since , ollowing KDIGO(Kidney Disease Improving GlobalOutcomes) recommenda-tions, we have extended treatmentto weeks to dene steroidresistance []. Following remission, the dose is reduced

to mg/m2 on alternate days or weeks and graduallytapered over months. Steroid dependence (SD) was

treated with the addition o levamisole (. mg/kg/day) onalternate days or cyclophosphamide (oral or intravenous).Steroid resistance was treated with oral ( mg/kg/day or

weeks) or intravenous ( mg/m2/month or months)cyclophosphamide, angiotensin converting enzyme (ACE)inhibitors, or cyclosporine. Since , cyclosporine ratherthan cyclophosphamide has become the preerred drug orthe management o steroid resistance []. Renal biopsieswere perormed by the paediatric nephrologists or steroidresistant or secondary cases o NS. issue was consideredadequate or reporting i at least glomeruli were present.

4. Definition of Terms [1,2]

erms are dened as ollows: remission: nil or trace protein-uria < mg/dL or consecutive days afer commencingtreatment; steroid resistant nephrotic syndrome (SRNS):ailure to achieve remission afer weeks o daily pred-nisolone; relapse: recurrence o mg/dL (+) proteinuriaor consecutive days afer having been in remission;steroid dependent nephrotic syndrome (SDNS): two con-secutive relapses during alternate day steroid therapy orwithin days afer cessation o steroids; requently relapsingnephrotic syndrome (FRNS): two or more relapses within months o initial response or relapses in any -monthperiod.

0

2

4

6

8

10

12

14

16

18

20

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Freq

uency

Age (years)

F : Age distribution o patients with nephrotic syndrome.

5. Statistical Analysis

Data was analysed using the Statistical Package or Social Sci-ences sofware version . Continuous data were representedas mean or median while categorical data were presentedas percentages. Signicance between steroid sensitivity andsome variables was determined using chi-square test whilecomparison o means was done with Students -test. A

value o


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108 patients

95 recordsSteroid sensitive NS, 72 (75.9%)Steroid resistant NS, 23 (24.2%)

Idiopathic NS, 87 (91.6%)Steroid sensitive, 72 (82.8%)Steroid resistant, 15 (17.2%)

Secondary NS, 8 (8.4%)All steroid resistant

5 deaths8 losses to follow-up

F : Flow chart o steroid sensitivity o patients with nephroticsyndrome.

relapsing, and children (.%) were steroid resistant.ime to remission in steroid sensitive patients ranged rom to days (median days).

Fifeen children were biopsied: with SRNS o whom had idiopathic SRNS and an -year-old male at presentation

on account o age, macroscopic haematuria, and hyperten-sion. Biopsy was not done in the others due to reusal toconsent, transer to another acility, or death. Histologicalndings were as ollows: ocal segmental glomerulosclerosis(FSGS) in (.%), minimal change disease (MCNS) in (%) and (.%) each o membranous nephropathy,membranoprolierative glomerulonephritis (MPGN), diffuseprolierative glomerulonephritis, and class lupus nephritis.Histologic patterns among the with idiopathic SRNS wereFSGSin (.%), MCNSin (%), and MPGN in (.%).

able shows a comparison o variables between thesteroid resistant and responsive groups. Lower serum albu-min, higher serum cholesterol, older age, haematuria, and

raised serum creatinine were all associated with steroidresistance. Only association with albumin and UI did notreach statistical signicance.

.. Outcome. Seven children (.%), all with SRNS, devel-oped chronic kidney disease (CKD) o whom progressed toend-stage kidney disease (ESKD) during the review period.One was with haemoglobin SS disease (HBSS) presentedin CKD while the others (SLE: ; FSGS: ; idiopathic: )developed CKD within years o diagnosis. Tere were deaths as ollows: complications o ESKD in (lupusnephritis: , FSGS:, and INS: ); AKI in patients, one owhom had lupus nephritis, and newly diagnosed patients

with undetermined steroid sensitivity oneo whom died roma cerebrovascular accident. Overall mortality was thereore.% but .% in those with SRNS.

7. Discussion

Our study revealed high prevalence o steroid sensitivityamong a cohort o black children with NS. In summaryabout % o the whole cohort and approximately % othe cohort with idiopathic childhood nephrotic syndromeachieved remission ollowing treatment with steroids. Tehigh proportion o steroid sensitivity in this study is remark-able because such high sensitivity has rarely been described

in a large sample o black children and ranks similar tothat described among children o other races []. Variousstudies describe NS in children o Arican descent as beingpredominantly steroid resistant and nonminimal change onhistology. In Nigeria, steroid resistance ranges between %and % among different geographical locations [,

]able , higher than the % in the current study. Doeet al. in Ghana [] reported steroid resistance o %amongst their cohort while Bhimmas group in South Arica[] reported about % steroid resistance among blackchildren. In the latter study, steroid sensitivity among Indianchildren in the same cohort was over % again highlightingracial differences in steroid sensitivity. Tis has led to therecommendation o a kidney biopsy as part o the initialevaluation o black children with NS.

Te reasons or this striking observation o high steroidsensitivity likely include the younger age structure o ourcohort. Te statistically signicant lower median age o thesteroid sensitive compared with steroid resistant patientssupports this. A small study rom southern Nigeria [] thatreported % steroid sensitivity had a young population witha mean age o . years. Asinobis group [] also rom Nigeriareported higher steroid sensitivity but their cohort comprisedonly children aged years. Tis age pattern is similar tothat reported among Caucasians and Asian children wherehigh steroid sensitivity has been reported []. For instance,in a report rom the United Kingdom [], median age ochildren with SSNS was . years compared with years inthose with SRNS. We thereore argue that age and race shouldbe considered together as strong predictors o response tosteroid rather than the sole reliance on race.

Another plausible explanation or the increased sen-sitivity observed in our cohort is the absence o certainpreviously prominent secondary aetiologies o NS in ourenvironment resulting in a relatively higher idiopathic pool,the majority o whom were steroid sensitive. Tis is a likelyconsequence o intensied efforts by the Government toreduce the burden o some childhood conditions in theregion. For instance, we did not diagnose any case o quartanmalaria nephropathy (QMN), which was previously reportedto be a leading cause o steroid resistant nephrotic syndromein our environment []. Previous Nigerian authors [,]have similarly alluded to the reduced incidence o QMNin the region. Malaria control programs have resulted inimproved access to antimalarial drugs over the last twodecades and this is likely to have contributed to the decline in

associated nephropathy. Does group in Ghana [] also oundno evidence o a tropical orm o nephrotic syndrome in theirpatients.In the same vein, in contrast with reports rom SouthArica [] and Ghana [], we did not diagnose inectionssuch as hepatitis and schistosomiasis, which we attributeto improved vaccination rates and access to portable water,respectively. Tese diseases have seemingly been replaced byothers like SLE and sickle cell anaemia, as also observed byOlowuetal.[]. Recent availability o diagnostic acilities orthe ormer andimproved survival beyond early childhood orthe latter could account or this observation.

Contrariwise, on the global scene, the incidenceo steroidresistant NS in various parts o the world such as the


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: Comparison o variables between steroid responsive and nonresponsive groups.

SSNS SRNS

Mean age (years) 5.8 3.9(median ) 8.8 4.8(median .) .

Age group (years/number) .

() (.%) (.%)

() (.%) (.%)> () (%) (%)

Serum albumin 2.1 0.8 1.9 0.8 .

Serum cholesterol 9.8 4.0 12.6 5.0 .

Hypertension () / (.%) / (.%) .

Haematuria () / (.%) / (%)


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presentation, hence advanced disease in two patients oneo whom presented with a cerebrovascular accident, alsocontributed to the high mortality reported.

In conclusion, our study reports high steroid sensitivityin a large group o black children. Although its retrospectivenature resulted in incomplete data in some cases, this was

compensated or by its large sample size. Tis study andew others in the region [,] suggest a changing patterno steroid sensitivity o childhood NS which may reect anadaptation to the changing epidemiology o some childhooddiseases as alluded to by previous authors. Surveillanceo the epidemiology o childhood NS and correspondingmodications in practice guidelines over time are thereorerecommended.

Conflict of Interests

Te authors declare that there is no conict o interestsregarding the publication o this paper.

Acknowledgment

Te authors thank the International Paediatric Nephrol-ogy Association or sponsorship o Fellowship raining inPaediatric Nephrology or aiwo Augustina Ladapo andChristopher Imokhuede Esezobor.

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