| Abstract|| |
To study the clinical indications and histopathological pattern of renal biopsies and renal resection specimens in the pediatric age group (birth to 17 years) in a large academic center in western Saudi Arabia. A retrospective review of the computerized database of the Pathology Department at King Abdul Aziz University Hospital (KAUH) was carried out on the final pathology reports of all children of the age of 17 years and below who either had ultrasound-guided renal biopsies or partial or total renal resections during the period between January 1995 and December 2008. All the specimens were reported by our pathology department. The most common clinical indication in the study group (242) is nephrotic syndrome (117, 48.3%), followed by systemic lupus erythromatosis for staging (30, 12.4%), nephritic syndrome (27, 11.1%) and renal mass for histological diagnosis (17, 7.0%). The most frequently reported pathological diagnosis was renal glomerulopathies, constituting 183 cases (n = 183, 75.6%) of the total number of pathology reports reviewed. Primary glomerulopathies were more common (n = 155, 88.4%) than the secondary ones (n = 28, 11.6%). The second most common pediatric renal pathology in this study was renal neoplasms (14, 5.7%). Vascular renal diseases and renal glomerulosclerosis ranked as the third pathological diagnosis in order of frequency in this study, with ten cases (10, 4.1%). The most common clinical indication for renal tissue sampling in this study is nephrotic syndrome and the most frequently detected pathology is glomerulonephritis. Larger multicentre studies are needed to further study pediatric nephropathies.
|How to cite this article:|
Abdullah LS. Histopathological pattern of pediatric renal diseases: A study from a university hospital in western Saudi Arabia. Saudi J Kidney Dis Transpl 2012;23:377-84
|How to cite this URL:|
Abdullah LS. Histopathological pattern of pediatric renal diseases: A study from a university hospital in western Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2014 Jul 29];23:377-84. Available from: http://www.sjkdt.org/text.asp?2012/23/2/377/93187
| Introduction|| |
Children in this country and worldwide are susceptible to a heterogeneous group of renal diseases. , There is, however, a paucity of recent large studies outlining the histopatho-logical spectrum of such diseases in developing countries. In Saudi Arabia, several small studies from different regions of the country have been published outlining the pattern of renal diseases in this age group. , The majority of these studies focused on the pattern of renal glomerulopathies, with particular attention to the primary ones, but the exact distribution of various types of kidney diseases including hereditary, vascular, infectious and neoplastic ones has not been well described in this age group. The present study outlines the distribution and frequency of all histopathological categories of renal diseases in the pediatric age group (from birth to 17 years of age) in a large academic center in the western region of Saudi Arabia.
| Materials and Methods|| |
A retrospective review of the computerized database of the Pathology Department at King Abdul Aziz University Hospital (KAUH) is carried out on the final pathology reports of all children of the age of 17 years and below who either had ultrasound-guided renal biopsies or partial or total renal resections in the period between January 1995 and December 2008. All the specimens were reported by our Pathology department. All renal resection specimens were routinely processed, stained and evaluated using the standard histological and, if required, histo-chemical and immunohistochemical techniques and all ultrasound-guided renal biopsies were examined using standard light microscopy, immunofluorescence study and electron microscopy. The medical record of these patients was reviewed and the demographic data such as age, sex, type of specimen (renal biopsy versus nephrectomy) and the clinical indication for the procedure were identified. The clinical indications were divided into 13 groups as follows: nephrotic syndrome, systemic lupus erythromatosis for staging, nephritic syndrome, abdominal mass, hematuria, end stage renal disease, proteinuria of the non-nephrotic type, obstructive uretro-pelvic junction/congenital kidney disease, hydronephrosis, transplant kidney disease, acute renal failure, congenital nephritic syndrome and kidney in-jury due to road traffic accident (RTA). The pathological diagnoses were categorized into hereditary renal diseases, congenital, obstructive uropathy, glo-merulonephritis (GN), kidney transplant reject-tion, tubulointerstitial nephritis, vascular renal diseases and glomerulosclerosis, renal neoplasms, normal, insufficient and others. For descriptive purposes and identification of age-specific clinical and pathological diagnoses, the cases were further subdivided according to patient's age into three subgroups as follows: age group A (birth to 5 years), group B (6-10 years) and group C (11-17 years).
The numbers and percentages of all cases related to each clinical indication and renal pathology in the study groups were identified and analyzed. The age-specific clinical and pathological diagnoses were also estimated according to age subgroup category (A, B, C).
The data were analyzed and tabulated in Excel sheets and the statistical analysis performed.
| Results|| |
The Department of Pathology at King Abdul Aziz University Hospital (KAUH) received, during the period between January 1995 and December 2008, 242 renal specimens (including renal biopsies and kidney resections) from children aged 17 and under, who underwent procedures for various clinical indications.
The age ranged from a newborn of two days old to one who was 17 years old. The majority of the cases (99 cases, 41%) were above the age of ten years; 85 cases (35%) were below the age of five years and 58 cases (24%) were between the ages of five and ten years. The sex distribution in the reported cases showed a similar pattern in both males (122 cases) and females (120 cases), with a male to female ratio of 1:1.
The number and percentages of various clinical indications for renal biopsy/resection are presented in [Table 1]. The most common clinical indication in the study group (242) was nephrotic syndrome (117, 48.3%), followed by systemic lupus erythematosus for staging (30, 12.4%), nephritic syndrome (27, 11.1%) and renal mass for histological diagnosis (17, 7.0%). Others included hematuria (13, 5.4%), end stage renal disease (13, 5.4%), obstructive uretro-pelvic junction diseases and other congenital kidney diseases (6, 2.5%), proteinuria of the non-nephrotic range (6, 2.5%), hydro-nephrosis (4, 1.6%), transplant kidney diseases (4, 1.6%), acute renal failure (2, 0.8%) and congenital nephritic syndrome (2, 0.8%). One renal specimen (1, 0.4%) was received with the clinical diagnosis of RTA. When the clinical indications are examined according to age subgroups [Table 2], nephrotic syndrome still represented the most common clinical diagnosis in the three age subgroups (A, B and C). The second most common clinical indication was abdominal mass in group A (age group less than five years), nephritic syndrome in group B (age group from six to ten years) and staging of lupus erythromatosis in group C (age group from 11 to 17 years). The third clinical indication in order of frequency was obstructive uretro-pelvic junction/congenital kidney diseases in the age group A, hematuria in the age group B and nephritic syndrome in age group C. The overall frequencies and percentages of renal pathologies in the study group (242) and according to specific pediatric age group are shown in [Table 3] and [Table 4]. The most frequently reported pathological diagnosis was renal glo-merulopathies constituting 183 (75.6%) of the total number of pathology reports reviewed. Primary glomerulopathies were more common (n = 155, 88.4%) than the secondary ones (n = 28, 11.6%). Among all cases of glomerulo-pathies, mesangioprolifrative glomerulonephritis was the most common diagnosis, with 48 cases (19.8%) with almost equal distribution in all age subgroups. This is followed by focal seg-mental glomerulonephritis as the second most common glomerulopathy (32, 13.2%), seen most commonly in the pediatric age group from birth to five years old and systemic lupus ery-thromatosis for staging as the third most common glomerulopathy (28, 11.6%), seen most commonly in the pediatric age group of 11-17 years. The remaining cases of primary glome-rulopathies included the following: IgM glo-merulonephritis (22, 9.1%), minimal change GN (18, 7.4%), membranous GM (12, 5.0%), acute post-infectious GM (8, 3.3%), IgA GN (8, 3.3%) and membranoproliferative GN (7, 2.9%). All cases of secondary GN in this study were found to be secondary to systemic lupus erythromatosis (28, 11.6%). The pattern of primary and secondary glomerulopathies is presented in [Table 5]. The second most common pediatric renal pathology in this study was renal neoplasms (14, 5.7%). In this pathological category, Wilm's tumor was the predominant one, constituting 11 of all 14 cases (4.5%) of renal neoplasms diagnosed. This was followed by clear cell sarcoma (2, 0.8%). A single case (0.4%) of lymphoma was identified while other categories of renal neoplasms, including renal cell carcinoma, rhabdoid tumors, mesoblastic neph-roma and angiomyolipoma, were not reported in our study. Renal neoplasms of all three types were most common in age group A.
|Table 1: The most common clinical indications for renal biopsy/resection in the study group (n = 242).|
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|Table 3: Histopathological pattern of renal diseases in pediatric age group (birth to 17 years).|
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|Table 4: Distribution of the most common renal pathologies according to specific pediatric age subgroups.|
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|Table 5: Frequency and percentage of glomerulonephritis in the pediatric study group.|
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Vascular renal diseases and renal glomerulo-sclerosis ranked as the third pathological diagnosis in order of frequency in this study, with ten cases (4.1%). Vascular renal diseases and renal glomerulosclerosis were most common in age group C. The remaining pathological diagnoses were as follows: Tubulointerstitial nephritis (9, 3.7%), hereditary renal diseases including Alport's syndrome and autosomal-recessive polycystic kidney disease (9, 3.7%) and congenital obstructive uropathy (vesicouretic reflux, duplex system) (8, 3.3%) of the total number of pathology reports reviewed.
Two cases (0.8%) were reported as of kidney transplant rejection and one (0.4%) as kidney laceration following RTA. The remaining two cases with the clinical indication of transplanted kidney disease showed tubulointers-titial nephritis. A single case (1, 0.4) case of renal biopsy was reported as normal and five (5, 2.1%) renal biopsies were reported as insufficient for diagnosis.
Majority of insufficient cases (four of five, 80%) were in the age group of 11-17 years. When the cases are analyzed according to age groups [Table 4], mesangioproliferative glo-merulonephritis remained the most common nephropathy in age groups A and B, while lupus erythromatosis for staging formed the most common nephropathy in the age group C.
Epidemiologic data available from countries around the world , show that children under the age of 17 years of age worldwide are susceptible to a wide spectrum of renal diseases including glomerulopathies, tubulinterstitial, vascular, congenital and neoplastic lesions. The prevalence of pediatric renal diseases varies in different countries due to differences in socio-economic, geographic and genetic factors, which play a role in developing and determining the pattern of such diseases in different parts of the world.  In the present study, the clinical and pathological pattern of pediatric renal diseases, in the western region of Saudi Arabia, is reported and compared with other national and international studies. The present study shows that the most common clinical indication for renal biopsy in the pediatric age group is nephrotic syndrome, followed by systemic lupus erythematosus for diagnosis and staging. This finding concurs with the previously published data both locally and internationally. ,,,,
When the histopathological pattern of the pediatric renal diseases in this study is compared with the available published data, both from Saudi Arabia and from other countries, ,, several similarities and differences are identified. In the current study, we observed that glomerulopathies, especially the primary ones, are the most common pediatric renal disease, comprising 75.6% of the total number of renal diseases reported. This is followed by renal neoplasms (5.8%) and vascular renal diseases/ glomerulosclerosis (4.1%). This finding concurs with the previously published data by Deshpande et al  from India, who observed that primary glomerular disease was the most common entity and comprised 61.5% of all the nephropathies. On the other hand, reports from other countries such as Tunisia and Iran , show some differences, identifying other entities such as hereditary nephropathies  and congenital urologic malformations,  including reflux nephropathies, obstructive uropathy and dysplastic kidneys as the most common ones. In a study from Tunisia,  the author studied the pathological findings only for cases with the diagnosis of chronic renal failure, which may explain the difference between that study and the present one.
Because glomerulopathies constituted the majo-rity of cases in this study, these cases were further analyzed and studied. On analysis of glomerulopathies, the present study show that mesangioproliferative GN is the most common glomerulopathy (48, 19.8%) as well as the most common renal nephropathy in the pediatric age group from birth to 17 years. This is followed by focal segmental glome-rulosclerosis (32, 13.2%), seen most commonly in the age subgroup A from birth to five years old. The present study also showed that systemic lupus erythematosus is the third most common glomerulopathy (28, 11.2%), seen most commonly in the age subgroup C (age 11-17 years).
When the incidence of pediatric primary and secondary glomeruopathy in this study is compared with previous studies from the same country, variable results were obtained. In two studies from the city of Riyadh by Alrasheed et al  and Murtala et al  , mesangioprolife-rative GN and focal segmental glomerulo-sclerosis (FSGS) were the two most common glomerulonephropatheis, while in two other studies from the same place, , other glome-rulopathies such as minimal change GN and FSGS were found to be the most common ones. Alrasheed et al  in his study of 167 renal biopsies from a university hospital in Riyadh concluded that nephrotic syndrome was the most common clinical indication for renal biopsy, accounting for 77% of all cases, and that mesangioproliferative GN (24%) and FSGS (24%) were the two most common primary GN. On the other hand, in the study by Jalah and Jamal  from the western region of Saudi Arabia, the authors reviewed a total of 169 cases of primary glomerular diseases and it was concluded that minimal change disease and FSGS were the most commonly encountered primary glomerulopathies (20.1% and 19.5%, respectively). Other glomerulo-pathies in that study were as follows: me-sangioproliferative IgM nephropathy (14.8%), IgA nephropathy (10.7%), post-infectious glo-merulonephritis (9.5%), mesangioproliferative glomerulonephritis with negative immunoflo-resence (5.9%). The difference between the above-mentioned study and the present one may be explained by the different range of pediatric age (1-18 years) covered in the mentioned study and the variability of diagnostic criteria used in categorizing primary glome-rular diseases between pathologists in different centers. Other reasons for discrepancy between the two studies include, the inclusion of more recent cases and the referral bias, as our center is a tertiary referral center commonly managing referred patients with already resistant nephrotic syndrome. The results of the present study showed considerable variability when compared with several international studies. ,,,,, A report from southern Croatia  showed similar distribution of glomerulopathies to the present study, with mesangiocapillay glomerulopathy as the most common one. Other studies show different results. In Turkey, Ozkaya et al  studied 392 Turkish children, 232 males and 160 females, diagnosed with nephrotic syndrome during the last ten years and were followed-up for at least two years. Two hundred and eighty patients in that study were diagnosed as minimal change GN based on initial presentation, laboratory features and clinical course. Kidney biopsy was performed on the remaining 112 children, and the results showed that membranoproliferative glomerulopathy was the most common histopatho-logical diagnosis, with 38 of 112 (34%) being that type of primary glomerulopathy. In another study by Kumar et al,  290 Indian children with the clinical diagnosis of nephrotic syndrome were reviewed histopathologically and focal segmental glomerulosclerosis was the most common histopathological subtype occurring in 112 of 290 children (38%). Other types of glomerulopathies in that study included minimal change GN (32%) and mem-branoproloiferative GN (15%). Mesangioproli-ferative GN on the other hand constituted only 11% of the total number of cases in that study.
Possible reasons for these differences in the histopathological pattern of pediatric nephro-pathies between different studies both within the same country and in different countries, in addition to the accepted geographic, racial and ethical differences, include the small number of patients in different studies, different clinical indications for histopathological examination, for example steroid-resistant versus non-steroid-resistant nephrotic syndromes, referral bias and, finally, the difference in availability of necessary diagnostic tools such as immunoflorescence and electron microscopy studies. The difference in the pattern of primary pediatric GN in different studies over several years may also be explained by the changing trends in the histopathology of idiopathic nephrotic syndrome in children noticed by many recent studies both from within this country as well as from western countries. , The studies prove a shift toward non-minimal change nephrotic syndrome in recent years, with increasing prevalence of primary glomerulopathies such as FSGN and membranoproliferative glomerulonephritis. Further larger studies are needed to confirm these findings taking into consideration the great impact it has on the management of children with nephrotic syndrome.
In the present study, the second most common nephropathy following glomerulopathies was renal neoplasms, constituting 5.8% of the total number of cases studied, and the most common pediatric renal neoplasm was Wilm's tumor, constituting (11.45%) of all nephropathies in this study.
As far as other nephropathies are concerned, no further analysis was carried out as the number of such nephropathies was very small for any meaningful and objective study.
Thus, it is apparent from this study that the incidence of various nephropathies, especially the glomerulopathies in the pediatric age group, varies within our country as well as from one country to another due to the previously mentioned reasons. The most common clinical indication for renal tissue sampling in this study is nephrotic syndrome and the most frequently detected pathology is glomerulo-nephritis. In order to overcome the difference in the incidence of such diseases and to have a better understanding of the natural history of pediatric nephropathies, more larger multi-centric studies, both national and international, are required to further study pediatric nephro-pathies. In this country, more centers across Saudi Arabia should join efforts to form a well-organized national renal registry.
| References|| |
|1.||Coppo R, Gianoglio B, Porcellini M, Maringhini S. Frequency of renal diseases and clinical indication for renal biopsy in children (Report of the Italian National Registry of Renal Biopsies in Children). Nephrol Dial Transplant 1998;13(2):291-5. |
|2.||Chadhaa V, Warady BA. Epidemiology of pe-diatric chronic kidney disease. Adv Chronic Kidney Dis 2005;12(4):343-52. |
|3.||Al-rasheed SA, Al-mugeiren MM, Al-Salloum AA, al-Sohaibani MO. Childhood renal diseases in Saudi Arabia. A clinicopathological study of 167 cases. Int Urol Nephrol 1996;2 8(5):607-13. |
|4.||Murtala AB, Elidrissy AW. Childhood renal disorders in Saudi Arabia. Peaditr Nephrol 1998;2:368-72. |
|5.||Saca E, Hazza I, ElImam O, Kawar M. Spectrum of biopsy proven renal disease in the pediatric age group at King Hussein Medical Centre. Jordanian Royal Med Serv 2007;14(1): 34-7. |
|6.||Bazina M, Glavina-Durdov M, Scukanec-Spoljar M, Bazina A. Epidemiology of renal disease in children in the region of southern croatia: A 10- year reveiew of regional renal biopsy databases. Med Sci Monit 2007;13(4): CR172-6. |
|7.||Deshpande G, Munjal R. Spectrum of nephro-pathies with special reference to primary glo-merulopathies. Med J Armed Force Inst 2000;56:125-9. |
|8.||Kamoun A. spectrum of pediatric diseases in Tunisia. Saudi J Kidney Dis Transpl 1997;8 (3):317-9. |
|9.||Ahmadzadeh A, Valavi E, Zangeneh-Kamali M, Ahmadzadah A. Chronic kidney disease in southern Iranian children. Iran J Pediatr 2009; 19(2):147-53. |
|10.||Mitwalli AH. Glomerulonephritis in Saudi Arabia: a review. Saudi J Kidney Dis Transpl 2000;11(4):567-76. |
|11.||Jalah S, Jamal A. Childhood primary glomerular diseases in the western region of Saudi Arabia. Saudi J Kidney Transpl 2009;20(4): 608-12. |
|12.||Ozkaya N, Cakar N, Ekim M, Kara N. Primary nephrotic syndrome during childhood in Turkey. Pediatr Int 2004;46(4):436-8 . |
|13.||Kumar J, Gulati S, Sharma AP, Sharma RK, Gupta RK. Histopathological spectrum of childhood nephrotic syndrome in Indian children. Pediatr Nephrol 2003;18(7):657-60. |
|14.||Kari JA. Changing trends of histopathology in childhood nephrotic syndrome in western Saudi Arabia. Saudi Med J 2002;23(3):317-21. |
|15.||Bonilla-Felix M, Parra C, Dajani T, et al. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int 1999;55(5):1885-90. |
Layla Saleh Abdullah
Pathology Department, College of Medicine, King Abdul Aziz University, P.O. Box 80215, Jeddah 21589
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]