Spectrum of Biopsy Proven Glomerular Disease in Children at Kanti Children ’ s Hospital

Introduction: Glomerular disease is one of the most common forms of renal disease and can have many different clinical presentations. However there is variation in the prevalence in the type of glomerular disease according to geographical location and race of population. The aim of the study was to find the overall distribution pattern of glomerular disease based on renal biopsies. Material and Methods: The medical records of all children who underwent kidney biopsy (n=29) between January 2012-june 2014 were analyzed. In this retrospective study we review children from Kanti Children’s Hospital, Nephrology Department. Demographic data including age, sex and indication of kidney biopsy as well as complication of the procedures were recorded. Result: A total number of thirty one biopsies were done. Two children were excluded from the study due to inadequate tissue and artifacts defects in preservative. The remaining twenty nine biopsies were included in the study and analyzed. Renal disease was found nearly equal in both male and female (51.72% vs. 48.27%).Mean age was 10.95±3.30 years. Maximum number of biopsies (75.86%) was performed between 1015 years. The most common indication of the kidney biopsy was nephrotic syndrome (steroid resistant nephrotic syndrome and steroid dependent nephrotic syndrome, 31.02% followed by lupus nephritis 27.58%.The most common glomerular disease were focal segmental glomerulosclerosis and lupus nephritis both contribute 27.58%. Among lupus nephritis class III was found more common (44.44%) in children. IgA nephropathy was also contribute (17.24%) in all glomerular disease. Regarding the kidney biopsy complication gross hematuria was observed in 6.89% of children which was self-limited. Conclusion: FSGS and lupus nephritis is becoming the most common glomerular disease in children attending the Kanti Children Hospital.IgA nephropathy was also contribute the glomerular disease in the children.


Introduction
K idney biopsy in the pediatric age group as in the adult popula on is one of the most important inves ga on in renal medicine.
In children the rate of undergoing kidney biopsy is not more than 10% as compared to adult 1 .Since the introduc on of percutaneous renal biopsy (PRB) in 1950's, technical advances in imaging and biopsy needle have simplifi ed and improve the success of the procedures.Though PRB is generally considered a safe but it is more diffi cult in children than adults due to size varia on and diff erent level of coopera on 2,3,4 .It can provide diagnos c precision, especially in glomerular disease, and also provides important informa on of prognos c value and about treatment op on 5 .However, there is a varia on in the prevalence of the types of glomerular disease according to geographical loca on and race of the popula on 6 .Glomerular disease is one of the most common forms of renal disease and can have many diff erent clinical presenta on.Glomerular diseases con nue to be the leading causes of end stage renal disease globally 6,7 .There is only few published data regarding the frequency of diff erent glomerulonephri s in Nepalese children in renal biopsies.Therefore, this was conducted to observe the spectrum of glomerular disease in children a ending the Kan Children's Hospitals.

Materials and Methods
All the kidney biopsies that were performed in Kan Children's Hospital, Nephrology Department over a period of two and half year from January 2012 to June 2014 were retrospec vely analyzed.A total thirty one biopsies were done.Two cases of renal biopsies were excluded from the analysis due to inadequate ssue and ar facts defect in preserva ve.Finally twenty nine biopsies were analyzed.Demographic data including age, sex, as well as indica on of kidney biopsy, the histopathological diagnosis and complica ons of the procedure were recorded.
Biopsies were done under midazolam premedica on, using Bard Disposable Core biopsy 18 G.Smaller children less than fi ve years, biopsies were done under ultrasound guidance and children more than fi ve years biopsies were done a er ultrasound guidance surface marking.Two specimens were taken for light microscope and for immunohistochemistry.All our biopsies were done as an inpa ent procedure and pa ents were observed for twenty four hours a er the procedure.
Nephro c syndrome was defi ned as clinical triad of heavy proteinuria (24 hours urine protein 40 mg/m 2 / hour or 2mg/mg), hypoalbuminemia and generalized edema.Steroid resistant nephro c syndrome was defi ned as persistent proteinuria of more than 40 mg/ m2/hour a er 8 weeks of daily dose of prednisolone therapy.Steroid dependent nephro c syndrome is defi ned as relapse while on alternate day steroid therapy or within 21 days of comple ng a successful course of prednisolone therapy.

Results
Over two and half year period, thirty one biopsies were performed, and two cases were excluded.Finally twenty nine biopsies were analyzed.Where male (n=14) and female (n=15) were nearly equal.Mean age was 10.95(±3.30)years, ranging from 22 months to 14 years.Among these 6.89% were aged under 5 years, 17.24% were 6-10 years and 75.86% were 11-14 years (Figure 1).FSGS, IgA nephropathy, lupus nephri s were more common between 10-14 years (Table 2).
The most common indica on for renal biopsy was nephro c syndrome 31.02%,among SRNS and SDNS was 24.13% and 6.89% respec vely.Suspected lupus nephri s was second most common indica on for biopsy (Table 1).
The most common glomerular disease was focal segmental glomerulosclerosis (FSGS) and lupus nephri s (27.58%).Among the lupus nephri s class III was the most common glomerular disease in children followed by class IV.IgA nephropathy was found 17.24% (Table 3).None of the biopsies shows minimal changes nephro c syndrome.Following the procedures 6.89% pa ents developed gross hematuria which was selflimited (Table 4).

Discussion
The study provides the spectrum of glomerular disease in children a ending the Nephrology Department at Kan Children's Hospital.In the present study, biopsy was done nearly equal in male and female.Study from Jordan shows requirement of biopsy was more common in male but female were more in Australia 1,6 .
The maximum numbers (75.86%) of biopsies are performed at 10-14 years of age.Printza et al. also men oned maximum numbers of biopsies were performed at 11-14 years (48%) 2 .This is because clinically up to age 10 years we treated as minimal change nephro c syndrome and biopsy was not regularly performed.The most common indica on for biopsy at our center was nephro c syndrome (SRNS and SDNS) followed by suspected lupus nephri s.Nephro c syndrome was the most frequent indica on for renal biopsy in United Kingdom (22.4%),Serbia as well as in India 4,6,9 .In our country nephro c syndrome was also common indica on for renal biopsy (81.6%) in adult 12 .Similar study done by Edward et al. shows nephro c syndrome (SRNS and SDNS) was common indica on for children and adult.However, SRNS and minimal changes nephro c syndrome was common indica on of biopsy shown by Pralad and Viswanath 1,12,13 .
In our study FSGS (27.58%) and lupus nephri s (27.58%) were the most common glomerular disease in children.The change in the spectrum of the glomerular diseases in the last few decades has been demonstrated in many studied worldwide with most showing a trend towards increase in FSGS cases 8 .Also in adult popula on FSGS is more common in India (80%), Nepal (81.6%),Bangladesh (20.41%) 6,10,11 .Various study shown that minimal changes disease (MCD) are the most common form of nephro c syndrome in children 12 .However this could be explained by the fact that those children with clinical and laboratory evidences of MCD were not subjected to kidney biopsy.Also in our study none of the children with MCD were included for renal biopsy.Golay et al. men oned lupus nephri s was most common secondary glomerulonephri s (73.38%) and uniformly the commonest causes of of secondary glomerulonephri s worldwide 7 .
In our study among 27.58% of lupus nephri s, class III corresponds to 44.44% followed by class IV but it was more common in eastern Nepal 13 .This varia on is due to diff erent geographical region and race of the popula on.In the present study, IgA nephropathy was found 17.24% in studied children but this is not consistent with the study done at Dharan, where IgA nephropathy was not reported.Golay et al. also men oned prevalence of IgA nephropathy is much lower in Nepal 7,11 .This discrepancy may be due to fact that Kan Children's Hospital is only pediatrics ter ary referral hospital and lack of published data in Nepal.Report from the Italian na onal registry of renal biopsies in children idiopathic IgA nephropathy was found most common (18.8%) 9 .Among the adult popula on IgA nephropathy was found 2.9% in Nepal 11 .
Following the procedure 6.89% children has developed gross hematuria.Our study is not consistent with the study done at Jordan (13.8%) and India (16.8%), which was nearly two mes higher than our study 1,14 .This diff erence is may be due to simplifi ed biopsy needle and ultra sound guidance biopsy in younger children.William et al. men oned gross hematuria occurs in 3.1% in adult 3 .

Conclusion
The most common indica on for the renal biopsy is nephro c syndrome and suspected lupus nephri s.FSGS and lupus nephri s is becoming the most common glomerular disease in children a ending the Kan Children's Hospital.IgA nephropathy is also contribu ng the glomerular disease in children.The procedure is proved to be safe.

Recommendation
Na onal registries for paediatric kidney biopsy should be established from hospitals of diff erent region of Nepal.

Table 1 :
Indica on for kidney biopsy:

Table 2 :
Histopathological diagnosis of children according to age category:

Table 3 :
Distribu on of Glomerular Diseases

Table 4 :
Procedure Complica on