| Abstract|| |
A total of 376 renal biopsies performed in several hospitals in Riyadh, on children with glomerulonephritis were reviewed. Focal segmental glomerulosclerosis (FSGS) was the most common glomerulopathy found and accounted for 120 cases (31.9%), followed by mesangial proliferative glomerulonephritis in 99 (26.3%). Minimal change nephrotic syndrome was seen in 55 (14.6%), membranoproliferative glomerulonephritis in 30 (8.0%), membranous glomerulonephritis in 18 (4.8%), IgA nephropathy in 15 (4.0%), post-infectious glomerulonephritis in 15 (4.0%), Alport syndrome in 14 (3.7%) and rapidly progressive glomerulonephritis in 10 (2.7%). Our findings show a high prevalence of FSGS in comparison with most international renal pathological studies published in children. At the same time, there is a relatively low prevalence of IgA nephropathy as compared to some other Asian countries. Additional, more comprehensive, clinical and pathological studies on Saudi children with glomerular diseases are needed to confirm or negate these findings. Environmental and genetic factors have to be explored and studied for their role related to these differences. Also, there is an urgent need to establish a glomerulonephritis registry for children in Saudi Arabia.
Keywords: Children, Glomerulonephritis, Riyadh, Saudi Arabia.
|How to cite this article:|
Al-Sabban E. Spectrum of Glomerular Disease Among Children in Saudi Arabia. Saudi J Kidney Dis Transpl 1997;8:285-8
| Introduction|| |
Children below 14 years of age represent about 51% of the total population of Saudi Arabia and the spectrum of glomerular disease in these children is not yet well determined. Glomerular disease remains a major cause of chronic morbidity in children. Attempts to explore this entity in Saudi Arabia have been made in the past and a few retrospective clinicopathological studies were published , . In the absence of a renal disease registry for Saudi children, a review of published and local experience of renal pathological studies was carried out and the data are presented in this paper.
| Material and Methods|| |
Three hundred and seventy six renal biopsy results were studied. Of them, 246 biopsies were performed at the King Faisal Specialist Hospital and Research Center or other hospitals in Riyadh excluding the University Hospital over a 10-year period (1981-1991). One hundred and thirty patients were biopsied at the King Khalid University Hospital. Riyadh over a 13-year period (April 1982 - September 1994)  . Patient age ranged between six months and 16 years. Male to female ratio was 3:2. Patients with congenital nephrosis and systemic disease-associated nephrosis were excluded. Indications for renal biopsy were similar in both groups of patients and included steroid resistant, steroid dependent, or frequently relapsing nephrotic syndrome, low complement associated nephrosis or if the patient presented for the first time with nephrotic syndrome beyond his 10th birthday. All biopsy samples were processed for light microscopy and immunofluorescent studies and in some cases, electron microscopy was carried out.
| Results|| |
Idiopatliic nephrotic syndrome of childhood was the major pathological entity found in 322 patients (85.6%). The biopsy findings of the 376 patients studied were as follows: 120 biopsy samples (31.9%) showed focal and segment al glomerulosclerosis, 99 (26.3%) showed diffuse mesangial proliferative glomerulonephritis (DMP) and 55 (14.6%) showed minimal change nephrotic syndrome (MCNS). Membranoproliferative glomerulinephritis (MPGN) was seen in 30 (8.0%); one showed MPGN type III, while 29 showed MPGN type I. Membranous nephropathy was diagnosed in 18 (4.8%), IgA nephropathy and post-infectious glomerulonephritis (PIGN) in 15 (4.0%) each, Alport syndrome in 14 (3.7%) and rapidly progressive glomerulonephritis (RPGN) in 10 patients (2.7%) [Table - 1].
| Discussion|| |
Glomerulonephritis is an uncommon renal disorder in childhood. Estimates of the annual incidence of nephrotic syndrome range from 2-7 new cases in children below 16 years of age per 100,000 total population , . The peak incidence is in the agegroup of 2 to 6 years  . Minimal change nephrotic syndrome (MCNS) is the most common cause of glomerular disease in childhood  . The most accurate non- invasive diagnostic tool of glomerular disease causing the nephrotic syndrome is the child's initial response to intensive treatment with prednisone  . About 93% of biopsy proven MCNS have been recorded to have responded to an initial eight-week treatment with prednisone with complete disappearance of proteinuria  . Accordingly, indications for renal biopsy in children have been revised world-wide in the last 15 years. Patients with steroid dependent or steroid resistant NS, or children presenting during their first year of life or beyond their tenth birthday, will be candidates for renal biopsy. Thus, it would be logical to expect that for any recent renal pathological review, MCNS would represent a small percentage of the total renal biopsies in children. Our review has shown that focal and segmental glomerulosclerosis is the most prevalent pathological lesion in the steroid dependent or steroid resistant nephrotic Saudi children. Similar findings have been reported by Mattoo, et al from the Maternity and Children's Hospital, Riyadh  . In contrast, FSGS is the third leading cause of glomerular disease in most internationally published pathological reviews of glomerular disease in children  . Although our criteria for renal biopsy were different from previously published studies, such a high prevalence of FSGS, may reflect genetic or environmental differences from the other parts of the world. On the other hand, this high prevalence of FSGS in Saudi children is a major concern since approximately 33.0% of the patients with nephrotic syndrome and FSGS progress to end-stage renal disease within five years of diagnosis, while another 33.0% remain with persistent heavy proteinuria  . Furthermore the risk of recurrence of FSGS in successfully matched renal grafts is about 25.0%, about half of whom loose their grafts at a later stage  .
The second most common diagnosis in our series was diffuse mesangial proliferative glomerulonephritis (DMP). Clinically, children with DMP are indistinguishable from those with minimal change nephrotic syndrome (MCNS) and their prognosis seems to be similar  .
Membranoproliferative glomerulonephritis was seen in 8% of our cases; MPGN Type I disease was diagnosed in 29 specimens. MPGN Type I is characterized by mesangial interposition and the presence of large subendothelial deposits in the lamina rara interna of the glomerular basement membrane. Most patients with MPGN have progressive renal injury leading to chronic renal failure. However, spontaneous sustained remission of disease has been reported in rare instances  .
Membranous nephropathy was diagnosed in 18 patients (4.8%); 17 patients presented with nephrotic syndrome, five of whom were positive for hepatitis B surface antigen among whom immunofluorescent staining for hepatitis surface antigen on renal biopsy was positive in three patients. In general, prevalence of membranous nephropathy in our series is consistent with international published figures ,, . The finding of membranous nephropathy secondary to hepatitis B infection in a relatively large number of patients can be explained by a high prevalence of hepatitis B surface anti-genemia (8.3%) that existed in the Saudi population  , prior to the launching of a nation-wide hepatitis B virus vaccination program in the Kingdom of Saudi Arabia in 1989.
Patients with IgA nephropathy usually present with recurrent microscopic or macroscopic hematuria; diagnosis can only be confirmed by renal biopsy. We found a prevalence of 4.0% in our pediatric population. The prevalence of IgA nephropathy in North America is between 210% , while it constitutes between 18 to 40% of all primary glomerular diseases in Japan  , Italy  and Australia  . Again, this may reflect environmental influence or different habitual or genetic factors. It is worthwhile mentioning that urine analysis screening program of school children in Japan most likely contributed to early detection and confirmation of IgA nephropathy by renal biopsy in this patient group. IgA nephropathy usually has a benign course in most children. However, rapidly progressive glomerulonephritis has been reported in children with IgA nephropathy leading to end-stage renal disease  .
Post-infectious glomerulonephritis (PIGN) was diagnosed in 15 children (4.0%), in most of whom, it was secondary to streptococcal infection. This does not reflect the true incidence of this entity in our pediatric population, since the acute clinical episode of glomerulonephritis is usually self limiting. Renal biopsy is rarely indicated in children with PIGN but should be considered only in cases with atypical presentation, such as nephrotic syndrome, anuria, significant azotemia, absence of serological evidence of preceding streptococcal infection or the persistence of low complement C3 levels for more than six weeks.
Electron microscopy showed changes consistent with Alport syndrome in 14 specimens (3.7%). Again, this figure may not reflect the true incidence of Alport syndrome in the Saudi population, since many patients with Alport syndrome develop insidious progressive renal insufficiency over many years, eventually presenting in their late teens with end-stage renal disease.
In conclusion, focal segmental glomerulosclerosis is the most common glomerular disease in Saudi children. Further comprehensive nationwide studies of glomerular disease is needed. The impact of the diagnosis of FSGS on the incidence of end-stage renal disease in Saudi children has to be evaluated. A renal disease registry for Saudi children needs to be established as soon as possible.
| References|| |
|1.||Akhtar M, Qunibi W, Taher S, et al. Spectrum of renal disease in Saudi Arabia. Ann Saudi Mcd 1990;lO(l):37-44. |
|2.||Abdurrahman AB, El-Idrissy ATH, Shipkey FH, Al-Rasheed S, AlMugeiren M. Clinicopathological features of childhood nephrotic syndrome in Saudi Arabia. Ann Trop Pediatr 1990;10:125-32. |
|3.||Al-Rasheed SA, Al-Mugeiren MM, AlSalloum AA, Al-Sohaibani MO. Childhood renal diseases in Saudi Arabia. A clinicopathological study of 167 cases. Int Urol Nephrol 1996;28(5):607-13. |
|4.||Schlesinger ER, Sultz HA, Mosher WE, Feldman JC. The nephrotic syndrome: its incidence and implications for the community. Am J Dis Child 1968;116:623-32. |
|5.||Rothenberg MB, Heymann W. The incidence of the nephrotic syndrome in children. Pediatr 1957;19:446-52. |
|6.||Lewis MA, Baildom EM, Davis N, Houston IB, Pestlethwaite RJ. Nephrotic syndrome: from toddlers to twenties. Lancet 1989;l:255-59. |
|7.||A Report of the InternationalStudy of Kidney Disease in Children. Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int 1978; 13:159-65. |
|8.||International Study of Kidney Disease in Children: The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 1981;98:561-64. |
|9.||Mattoo TK, Mahmood MA, Al-Harbi MS. Nephrotic syndrome in Saudi children clinicopathological study of 150 cases. Pediatr Nephrol 1990;4:517-19. [PUBMED] |
|10.||Broyer M, Meyrier A, Niaudet P, Habib R. Minimal changes and focal segmental glomerulosclerosis. In: Cameron S, Davison AM, Grunfeld JP, Kerr D, Ritz E, eds. Oxford textbook of clinical nephrology. Oxford; Blackwell 1992;298- 339. |
|11.||Cameron JS. Recurrent primary disease and de novo nephritis following renal transplantation. Pediatr Nephrol 1991;5:412-21. [PUBMED] |
|12.||Habib R, Girardin E, Gagnadoux MF, Hinglais N, Levy M, Broyer M. Immuno-pathological findings in idiopathic nephrosis: clinical significance of glomerular Immune deposits. Pediatr Nephrol 1988;2:402-8. [PUBMED] |
|13.||Habib R, Kleinknecht C, Gubler MC, Levy M. Idiopathic membrano proliferative glomerulonephritis in children. Report of 105 cases. Clin Nephrol 1973;1:194-214. |
|14.||Ramirez F, Brouhard BH, Travis LB, et al. Idiopathic membranous nephropathy in children. J Pediatr 1982;101:677-81. [PUBMED] |
|15.||Locard-Bisot S, Cochat P, Gilly J", et al. Membranous glomerulonephritis in children: 20 cases. Pediatrics 1990;45:527-32. |
|16.||Trainin EB, BoichisH, Spitzer A, Greifer I. Idiopathic membranous nephropathy. Clinical course in children. NY State J Med 1976;76:357- 60. |
|17.||AI-Faleh FZ. Clinical review: hepatitis B infectionin Saudi Arabia. Ann Saudi Med 1988;8(6):474-80. |
|18.||Hood SA, Veiosa JA, Holley KE, Donadio JR Jr. IgA-IgG nephropathy: predictive indices of progressive disease. Clin Nephrol 1981;16:55-62. |
|19.||Katz A, Walker JK, Landy PJ. IgA nephritis with nephrotic range proteinuria. Clin Nephrol 1983;20:67-71. |
|20.||Kitajima T, Murakami M, Sakai O. Clinicopathological features in Japanese patients with IgA nephropathy. Jpn J Med 1983,-22:219-22. [PUBMED] [FULLTEXT]|
|21.||Berger J, Yavena H, Crosnier J. La glomerulonephrite a depots mesangiaux d' IgA: une cause frequente d' insuffisance renale terminale. Nouv Press Med 1980;9:219-21. |
|22.||Clarkson AR, Seymour AE, Thompson AJ, Haynes WDG, Chan YL, Jackson B. IgA nephropathy: a syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 1977;8:459-71. |
|23.||Welch TR, McAdams AJ, Berry A. Rapidly progressive IgA nephropathy. Am J Dis Child 1988;142:789. [PUBMED] |
Head, Division & Pediatric Nephrologist, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211
[Table - 1]