Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric nephrology practice. There is currently little information in the literature on the spectrum of histopathologic lesions in children presenting with SRNS in Pakistan. This study was designed to determine the histopathologic lesions in children presenting with SRNS at our center. The study was conducted at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from January 2009 to August 2011. All children (≤16 years) presenting with SRNS, in whom renal biopsies were performed, were included. Their demographic, clinical, laboratory, and histopathological data were retrieved from files and original renal biopsy forms. The results were analyzed by SPSS version 10.0. A total of 147 children were included. Of these, 91 (61.9%) were males and 56 (38.1%) females, with male-to-female ratio of 1.6 : 1. The mean age was 7.03 ± 4.0 years (range: 6 months–16 years). The histopathological lesions seen on renal biopsies comprised of focal segmental glomerulosclerosis (FSGS) (38.5%), followed by minimal change disease (MCD) (23.2%), IgM nephropathy (IgMN) (13.6%), idiopathic mesangial proliferative GN (10.2%), membranous GN (8.2%), and mesangiocapillary GN (4.8%). Our results indicate that FSGS is the predominant lesion in children with SRNS, followed by MCD and IgMN.
Steroid-resistant nephrotic syndrome (SRNS) is a common problem in pediatric nephrology practice and one that poses significant therapeutic challenge for pediatric nephrologists [
This study was thus designed to determine the spectrum of histopathological lesions in children presenting with SRNS at our center.
This descriptive, observational study was conducted from January 2009 till August 2011 at the Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT). All children presenting with SRNS at the Pediatric Nephrology Outpatient Department of SIUT and in whom renal biopsies were performed during the above-mentioned period were included. Their demographic, clinical, and laboratory data at the time of presentation and on last followup were retrieved from case files. The histopathological findings including light microscopy (LM) and immunoflourescence (IF) findings were recorded from original renal biopsy forms. Standard definitions of the disease and treatment responses were used as in our previous study [
At our center, two cores of native renal biopsy are routinely obtained for full pathologic evaluation as described in detail in our previous paper [
For LM, routinely 10 serial sections are cut and stained by hematoxylin and eosin (H and E), Masson’s trichrome, periodic acid-Schiff (PAS), and silver stains (Gomori’s methenamine silver, GMS). In our laboratory, renal tissue sections are cut at a thickness of 2 um for optimal evaluation of the morphologic details as reported previously [
Tissue specimens for IF are snap-frozen in liquid nitrogen and cut on cryotome. The tissue is stained by the direct method using fluorescein isothiocyanate- (FITC-) conjugated antisera monospecific for IgG, IgA, IgM, C3, and C1q (Dako, Glostrup, Denmark). The slides are visualized under the epifluorescense microscope and graded semiquantitatively as 0 to 3+ (on a scale of 0 to 3+, where 0 = absent and 3+ = brightest) and distribution described as membranous or mesangial in a granular or liner pattern as described previously [
Tissue samples for EM were processed as described in our previous report [
This was made by correlating the entire clinical, laboratory, and the pathological findings. The final diagnosis was retrieved from the original renal biopsy reports. Standard definitions of the diseases were utilized for the pathological categorization of the glomerular lesions as in our previous study, and shown in Figures
Medium-power view showing a glomerulus with segmental scarring associated with intracapillary foam cells and adhesion formation with Bowman’s capsule, in a case of classic focal segmental glomerulosclerosis. (Silver stain, ×200).
Low-power view of a representative section of a renal biopsy showing five glomeruli with minor changes. There is no segmental scarring or significant mesangial proliferation. One small artery included as well as the surrounding tubulointerstitial compartment show no significant pathology. This case was diagnosed as minimal change disease after IF study showed negative results and EM showed diffuse effacement of foot processes. (Silver stain, ×100).
Medium-power view showing a glomerulus with mild mesangial prominence, but no significant increase in mesangial hypercellularity. This case latter turned out to be IgM nephropathy after IF showed diffuse granular mesangial positivity of IgM, as shown in Figure
Medium-power view showing a glomerulus with diffuse granular mesangial positivity of IgM on IF study. (IgM, ×200).
Statistical analysis was carried out using IBM compatible SPSS for windows version 10.0 (SPSS, Chicago, IL, USA). Simple descriptive statistics such as
A total of 147 pediatric patients with SRNS and in whom percutaneous renal biopsies were performed were included. Of these, 91 (61.9%) were males and 56 (38.1%) females with the male-to-female ratio of 1.6 : 1. The mean age at presentation was
Patient characteristics.
Total number of patients | 147 |
---|---|
Males | 91 (61.9%) |
Females | 56 (38.1%) |
Male-to-female ratio | 1.6 : 1 |
Mean age (in years) | |
Age range | (6 months–16 years) |
The spectrum of histopathological lesions seen on renal biopsies was wide and comprised of focal segmental glomerulosclerosis (FSGS) (38.7%), followed by minimal change disease (MCD) (23.1%), IgM nephropathy (13.6%), idiopathic mesangial proliferative GN (MesPGN) (10.2%), membranous GN (MN) (8.2%), mesangiocapillary or membranoproliferative GN (MPGN) (4.8%), and a number of rare lesions (Table
The frequency distribution of different histopathological lesions in 147 pediatric patients with steroid-resistant nephrotic syndrome.
Pathological lesions | Frequency | Percentage |
Focal segmental glomerulosclerosis | 57 | 38.7 |
Minimal change disease | 34 | 23.1 |
IgM nephropathy | 20 | 13.6 |
Mesangioproliferative GN | 15 | 10.2 |
Membranous GN | 12 | 8.2 |
Mesangiocapillary GN | 7 | 4.8 |
IgA nephropathy | 1 | 0.6 |
Chronic sclerosing GN | 1 | 0.6 |
Total | 147 | 100 |
Comparison of histopathological lesions of our study with local and international studies (all figures are in percentages).
Histopathological lesions | Our study | Olowu et al. [ | Kari et al. [ | Gulati et al. [ | Azhar et al. [ |
---|---|---|---|---|---|
FSGS | 38.7 | 39.1% | 39 | 58.8 | 28.8 |
MCD | 23.1 | 4.3 | 8 | 17.6 | 13.3 |
IgMN | 13.6 | — | 28 | — | 17.6 |
MesPGN | 10.2 | 8.7 | 17 | 17.6 | 8.8 |
MN | 8.2 | 4.3 | — | 1.4 | 13.3 |
MPGN | 4.8 | 43.5 | — | 1.6 | 11.5 |
IgAN | 0.6 | — | 3 | — | 6.6 |
FSGS: focal segmental glomerulosclerosis; IgANL: IgA nephropathy; IgMN: IgM nephropathy; MCD: minimal change disease; MesPGN: mesangioproliferative GN; MN: membranous GN; MPGN: mesangiocapillary or membranoproliferative GN.
This is one of the largest studies on the spectrum of histopathological lesions underlying SRNS in children and adolescents from a single center located in the southern metropolitan city of Karachi in Pakistan. We believe that the results of this study represent the true pattern of glomerulopathies in children presenting with SRNS from this part of the world. This is because our renal pathology laboratory is the only laboratory in the country that is equipped with all the necessary modalities including IF and EM that are required for the complete evaluation of renal biopsies. This may seem a routine matter in most of the laboratories in the developed world, but the situation in developing countries is just the opposite. Moreover, although our center is located in the southern part of the country and our catchment area mostly comprises of southern provinces of Sindh and Balochistan, but we receive patients from all over the country. This is because SIUT offers free consultation and treatment to all patients with kidney diseases [
There is still controversy over the role of renal biopsy in the management of SRNS children [
The results of our study are generally similar to those previously reported in the literature. All the previously reported studies have observed a higher prevalence of FSGS in this form of INS [
Overall, MCD is the most common cause of INS in children, especially under six years of age. However, its incidence in SRNS is lower than that of FSGS in most of the reported studies [
IgMN is a relatively new entrant to the list of glomerulopathies underlying INS both in children and adults. However, its status as a distinct entity or even its existence is under debate till date. The disease was first described in 1978 by two independent groups of investigators [
MN was less common in our children with SRNS as in almost all previously published series on this subject [
In conclusion, our results indicate that FSGS is the predominant lesion in children with SRNS, followed by MCD and IgMN. The study defines the true spectrum of histopathological lesions underlying SRNS in children in Pakistan.
The authors declare that they have no conflict of interests.
The authors declare that the research protocol has been approved by ethical review committee of SIUT and it conforms to the provisions of the Declaration of Helsinki. They also declare that the results presented in this paper have not been published previously in whole or part, except in abstract form.
The authors also declare that they all have contributed significantly to the study and that they all are in agreement with the contents of the paper.