Spectrum of Renal Disease in Saudi Arabia

Transcription

1 Mohammed Akhtar, MD; Wajeh Qunibi, MD; Saadi Taher, FRCP; Earl Ginn, MD; Osman Furayh, MD; Sami Sanjad, MD; Essam Al-Sabban, MD From the Departments of Pathology and Laboratory Medicine (Dr. Akhtar), Medicine (Drs. Qunibi, Taher, Ginn, and Furayh), and Pediatrics (Dr. Al- Sabban and Dr. Sanjad), King Faisal Specialist Hospital and Research Centre, Riyadh. Address reprint requests and correspondence to Dr. Akhtar: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Accepted for publication 2 July A series of 380 kidney biopsies performed at several institutions in Saudi Arabia was reviewed and categorized as follows: primary glomerular disease, 275; renal involvement in systemic disease, 77; and miscellaneous, 28. The 275 biopsy specimens from patients with primary glomerular disease were further classified and revealed minimalchange disease in 16 (5.8%), mesangial proliferative glomerulonephritis in 80 (29.09%), focal segmental glomerulosclerosis in 96 (34.9%), mesangiocapillary glomerulonephritis in 29 (10.5%), membranous glomerulonephritis in 18 (6.5%), IgA nephropathy in 16 (5.8%), rapidly progressive glomerulonephritis in 12 (4.4%), and postinfectious glomerulonephritis in 8 (2.9%). Comparison of our findings with those from previously published studies indicated that the frequency of focal segmental glomerulosclerosis in our series is higher than that for most series reported for other countries, while the incidence of IgA nephropathy is relatively low. Another significant difference was a complete absence of mesangiocapillary glomerulonephritis type II (dense-deposit disease). Additional studies are needed to further confirm these findings and identify the factors responsible for the differences. M Akhtar, W Qunibi, S Taher, E Ginn, O Furayh, S Sanjad, E Al-Sabban, Spectrum of Renal Disease in Saudi Arabia. 1990; 10(1): Renal disease is an important cause of morbidity and mortality in the Saudi population. However, there have been only a few studies dealing with the prevalence of various types of renal diseases in the country. 1-4 In a study based on 147 renal biopsies and published from our institution, a relatively high proportion of focal segmental glomerulosclerosis (FSGS) and a low frequency of membranous glomerulonephritis (MGN) and amyloidosis were noted. 3 A subsequent study from another hospital in Riyadh revealed a relatively high frequency of mesangial proliferative glomerulonephritis (MPGN). 4 At King Faisal Specialist Hospital and Research Centre, we have had the opportunity to study large numbers of kidney biopsy specimens obtained at our hospital and several other institutions from within the Kingdom. These specimens were reviewed in order to establish the spectrum of renal disease in Saudi Arabia. It is hoped that, since the specimens in our series come from several institutions, our findings will reflect more accurately the relative proportion of various renal diseases in the country.

2 Material and Methods A total of 544 renal biopsy specimens examined in our laboratories between July 1983 and August 1988 were reviewed. Of them, 57 were excluded because of insufficient amount of tissue (27), end-stage renal diseases (14), nonspecific changes (11), or no significant abnormalities (5). Another 107 biopsies obtained from transplanted kidneys were also excluded. The remaining 380 biopsies form the subject of this report. Two hundred fourteen biopsies were done at King Faisal Specialist Hospital and the remaining 166 biopsy specimens were obtained from several hospitals throughout Riyadh and other parts of the Kingdom. More than one specimen from the same patient was counted as one. Attempt was made to study all tissue by light microscopy as well as immunofluorescent and electron microscopy, but in some cases either immunofluorescent or electron microscopy could not be performed because of insufficient tissue. Specimens received from institutions outside Riyadh were studied only by light and electron microscopy. Thus, 310 biopsies were examined by electron microscopy and 356 by immunofluorescent microscopy. Patient age varied from 3 months to 76 years; 156 patients were 16 years or younger, and 224 were older than 16. There were 203 males and 177 females. The ethnic mix was as follows: 304 patients (80%) were Saudi, 65 (17%) were expatriates, and 11 (3%) patients were of unknown nationality. Results The 380 biopsies were classified into three groups: primary glomerular disease, 275 (72.4%); renal involvement in systemic diseases, 77 (20.2%); and miscellaneous, 28 (7.4%). The 275 biopsies showing primary glomerular disease were further divided into several groups, according to diagnosis, and these were additionally divided into adult and pediatric patient groups (Table 1). Minimal-Change Disease, Mesangial Proliferative Glomerulonephritis, and Focal Segmental Glomerulosclerosis Of the 275 biopsies with primary glomerular disease, 96 (34.9%) showed FSGS, 80 (29.1%) showed MPGN, and 16 (5.8%) showed minimal-change disease (MCD). Patients in the pediatric age group showed the following proportions: FSGS (40.1%), MPGN (29.9%), and MCD (11%). Figures 1 to 3 show typical microscopic findings for these three diseases. Mesangiocapillary (Membranoproliferative) Glomerulonephritis Twenty-nine biopsies revealed mesangiocapillary glomerulonephritis (MCGN), representing 10.5% of the cases of primary glomerular disease. Patient age in this group ranged from 7 to 54 years and there were 17 males and 12 females (male to female ratio, 1.5:1). Twenty-seven (93%) of the patients had type I MCGN, and two (7%) had type III. None of the biopsies revealed type II MCGN (dense-deposit disease). Table 1. Relative incidence of various lesions in patients with primary glomerular disease. Type of All patients Adults Children lesion no. (%) no. (%) no. (%) MCD 16( 5.8) 2( 1.3) 14(11.0) MPGN 80(29.1) 42(28.3) 38(29.9) FSGS 96(34.9) 45(30.4) 51(40.1) MCGN 29(10.5) 22(14.8) 7( 5.5) MGN 18( 6.5) 16(10.8) 2( 1.5) IgAN 16( 5.8) 9( 6.0) 7( 5.5) RPGN 12( 4.4) 9( 6.0) 3( 2.3) PIGN 8( 2.9) 3( 2.0) 5( 3.9) Total MCD = minimal-change disease; MPGN = mesangial proliferative glomerulonephritis; FSGS = focal segmental glomerulosclerosis; MCGN = mesangiocapillary (membranoproliferative) glomerulonephritis; MGN = membranous glomerulonephritis; IgAN = IgA nephropathy; RPGN = rapidly progressive (crescentic) glomerulonephritis; PIGN = postinfectious glomerulonephritis.

3 Figure 1. (Left) A glomerulus showing features of minimal-change disease. The capillaries and mesangium are within normal limits. (Hematoxylin-eosin; original magnification, 250.) (Right) A glomerulus from minimal-change disease featuring essentially normal mesangial areas and capillary basement membranes. (Jones Stain; original magnification, 250.) Figure 2. (Left) A representative glomerulus from mesangial proliferative glomerulonephritis. There is mild diffuse mesangial prominence. (Hematoxylin-eosin; original magnification, 250.) (Right) Diffuse mesangial prominence in mesangial proliferative glomerulonephritis. (Jones stain; original magnification, 250.) Figure 3. (Left) Glomerulus with a typical area of segmental sclerosis in a renal biopsy with focal and segmental glomerulosclerosis. (Hematoxylin-eosin; original magnification, 250.) (Right) Glomerulus with focal and segmental glomerulosclerosis, but only part of the glomerulus is involved by sclerosis. (Jones stain; original magnification, 250.)

4 Rapidly Progressive (Crescentic) Glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) was seen in 12 of the biopsies, constituting 4.4% of the cases of primary glomerular disease. Patient age ranged from 8 to 50 years and there were seven male and five female patients. An underlying pathogenic mechanism was immune complex disease in nine and anti-glomerular basement membrane (GBM) disease in one. No underlying immunological process could be found in the remaining three patients. Membranous Glomerulonephritis MGN was seen in 18 (6.5%) of the biopsies from patients with primary glomerular disease. Patient age ranged from 7 to 54 years and there were seven male and 11 female patients (male to female ratio, 1:1.5). IgA Nephropathy IgA nephropathy. (IgAN) was diagnosed in 16 specimens, representing 5.8% of the cases of primary glomerular disease. The age range in this group of patients was 3 to 48 years. There were 11 male and five female patients (male to female ratio, 2:1). Two of the patients belonged to a single family, suggesting the possibility of familial IgAN. Postinfectious Glomerulonephritis A diagnosis of postinfectious glomerulonephritis (PIGN) was rendered in eight (2.9%) of the specimens from patients with primary glomerular disease. The age of these patients ranged from 6 to 29 years;six were male and two were female (male to female ratio, 3:1). Renal Involvement in Systemic Disease Lupus nephritis was diagnosed in 36 of the biopsies. The age range for this group of patients was 12 to 53 years and seven were male and 29 were female (male to female ratio, 1:4). Using WHO classification, the glomerular lesions were classified as follows: Class I (1), Class II (3), Class III (5), Class IV (16), Class V (6), Class III and V (4), and Class IV and V (1). Renal involvement in association with several other systemic diseases was noted in an additional 41 biopsies. Details of these cases are given in Table 2. Miscellaneous Group There were 28 biopsies in this group. The various diagnoses in these biopsies are given in Table 3. Comparison with Biopsy Series from Other Countries The results from our study were compared with those from a number of studies published from different parts of the world. Valid comparison, however, was not always possible because the study designs varied concerning both the criteria for patient selection as well as the extent of the pathological investigations. This could affect the pathological characterization. Other problems encountered include: some studies excluded adults and others children; some studies only included patients with nephrotic syndrome whereas others included all patients with glomerular disease. In some series, all patients with nephrotic syndrome underwent biopsy, while in others only patients with steroid-resistant or frequently relapsing nephrotic syndrome had biopsy specimens taken. Electron microscopy and immunofluorescent studies were also not consistently done in all studies.

5 Disease Table 2. Renal involvement in systemic disease. Lupus nephritis 36 No. Hemolytic uremic syndrome 8 Henoch-Schonlein purpura 7 Severe hypertension 7 Amyloidosis 4 Diabetes 4 Vasculitis 3 Sjogren's disease 1 Behcet's disease 1 Sarcoidosis 1 Subacute bacterial endocarditis 1 Scleroderma 1 Sickle cell disease 1 Glycogen storage disease 1 Total 77 Diagnosis Table 3. Details of miscellaneous diagnosis in 28 biopsies. Unexplained immune complex glomerulonephritis 4 Benign familial hematuria 5 Acute tubular necrosis 5 Interstitial nephritis 4 Pre-eclampsia 2 Post-partum renal failure 3 Oxalosis 1 Infantile polycystic disease 1 Fanconi's syndrome 1 Alport's syndrome 2 Total 28 No. Tables 4 and 5 show data from these studies that have been recalculated to indicate the relative frequencies of the various lesions in a comparable manner. The category of primary glomerular nephritis is heterogeneous and includes IgAN and mesangial proliferative, diffuse endocapillary, focal proliferative, and crescentic glomerulonephritis. It would be more appropriate to subdivide this category but the information from the other published studies is not adequate enough to allow this. Discussion The most frequently diagnosed lesion in patients with primary glomerular disease was FSGS and this represented 34.9% of the cases. Among the adult and pediatric patients, it constituted 30.4% and 40.1% of the cases, respectively. In most countries the frequency of FSGS is less than 15% (Tables 4, 5). However, a higher incidence of FSGS has been reported from Hong Kong 5 (23.6% adults), Iran 6 (31.6% pediatric), and Ghana 7 (36% adult). Thus it appears that the frequency of FSGS in Saudi Arabia is higher than that elsewhere in the world. The reasons for this, however, are not understood. Since King Faisal Specialist Hospital and Research Centre, where most of the biopsy specimens originated, is a tertiary care hospital, it tends to receive more patients with steroid-resistant nephrotic syndrome and this could account for the high frequency of FSGS. However, since the relative proportion of other causes of steroid-resistant nephrotic syndrome such as MGN and MCGN is not increased in our series, we believe that the patient selection inherent in the pattern of referral is probably not a significant factor. Furthermore,

6 since many of the published series also originated from tertiary care institutions, patient selection may not alone account for the high frequency of FSGS in our patients. Additional epidemiological studies are needed to understand the various factors responsible for the high frequency of FSGS in Saudi Arabia. Table 4. Relative frequency of various types of glomerular lesions among adults in different countries. No. of Country patients MCD FSGS PGN* MCGN MGN South Africa (black) (10.7%) 9( 3.5%) 72(28.5%) 90(35.7%) 54(21.4%) South Africa (Indian) (21.3%) 3( 4.0%) 30(40.0%) 10(13.3%) 16(21.3%) Tunisia (16%) 49(16%) 91(30%) 51(16.9%) 64(21%) Sudan (17%) 5(12%) 15(38%) 13(33%) Singapore (31.3%) 66(10.9%) 316(52%) 14( 2.3%) 21( 3.5%) Hong Kong (27.7%) 64(23.6%) 59(21.8%) 29(10.7%) 44(16.2%) Malaysia (49.3%) 54( 6.2%) 306(35.3%) 24(2.71%) 55( 6.3%) United Kingdom (30.5%) 30(11.0%) 43(15.8%) 47(17.2%) 69(25.3%) India (29%) - 38(39%) 16(16%) 16(16%) Ghana (10%) 11(36%) 8(25%) 4(13%) 5(16%) Saudi Arabia (present study) 148 2( 1.3%) 45(30.4%) 63(42.5%) 22(14.8%) 16(10.8%) *PGN includes IgA nephropathy, diffuse endocapillary proliferative glomerulonephritis, focal proliferative glomerulonephritis, crescentic glomerulonephritis, and mesangial proliferative glomerulonephritis. PGN = primary glomerulonephritis; MCD = minimal-change disease; FSGS = focal segmental glomerulosclerosis; MCGN = mesangiocapillary (membranoproliferative) glomerulonephritis; MGN = membranous glomerulonephritis. Table 5. Relative frequency of various types of glomerular lesions among pediatric patients in different countries. Country No. of patients MCD FSGS PGN* MCGN MGN South Africa (black) (14.9%) 4( 5.9%) 20(29.8%) 6( 8.9%) 27(40.2%) South Africa (Indian) (79.2%) 2( 3.7%) 5( 9.4%) 2( 3.7%) 2( 3.7%) Kenya (20.8%) 5(10.4%) 23(48%) 5(10.4%) 5(10.4%) India (80%) 11( 5.8%) 19(10.1%) 4( 2.1%) 3( 1.6%) Iran (22.9%) 98(31.6%) 78(25.1%) 47(15.2%) 16( 5.2%) International study (76.4%) 45( 8.6%) 31( 6.0%) 39( 7.5%) 8( 1.5%) Hong Kong (45.6%) 10( 8.7%) 30(26.3%) 2( 1.7%) 20(17.7%) France (54.0%) 47(12.1%) 41(10.5%) 53(13.6%) 37( 9.5%) Saudi Arabia (present study) (11.0%) 51(40.1%) 53(41.7%) 7( 5.5%) 2( 1.5%) *PGN includes IgA nephropathy, diffuse endocapillary proliferative glomerulonephritis, focal proliferative glomerulonephritis, crescentic glomerulonephritis, and mesangial proliferative glomerulonephritis. MCD = minimal-change disease; FSGS = focal segmental glomerulosclerosis; PGN = primary glomerulonephritis; MCGN = mesangiocapillary (membranoproliferative) glomerulonephritis; MGN = membranous glomerulonephritis. The second most common diagnosis in our series was MPGN. This lesion is characterized histologically by the presence of mild to moderate mesangial hypercellularity with varying degrees of expansion of the mesangial matrix Immuno-fluorescent microscopy usually will reveal mesangial IgM deposition. Clinically this disease is closely related to other causes of idiopathic nephrotic syndrome, such as MCD and FSGS. There is considerable controversy in the literature regarding the significance of mesangial proliferation and/or mesangial IgM deposition. Some believe that these features have no prognostic significance and regard them as part of the spectrum of MCD; others argue that the changes indicate a poorer prognosis and should therefore be distinguished from MCD In some series, mesangial prominence and IgM deposition have been categorized separately as diffuse mesangial proliferation and IgM nephropathy. 8,9 In view of this lack of uniformity regarding the reporting of MPGN, a meaningful comparison of its relative frequency with that from other series is not possible. The diagnosis of IgAN was made in 16 (5.8%) of the cases of primary glomerular disease. This figure varies considerably from one country to another. These countries can be categorized into three groups according to the relative incidence of IgAN: Group 1 (less than 15%): U.S.A., Canada, U.K., Mexico, Chile, Brazil, Tunisia, Thailand, Switzerland, Portugal, India, New Zealand, Hungary; Group 2 (15-30%): France, Scandinavia, West

7 Germany, Bulgaria, Italy, Spain, Malaysia, Australia, Israel, Netherlands; Group 3 (more than 30%): Japan, China, Taiwan, Hong Kong, Singapore, Korea. 13 From our data, it appears that Saudi Arabia belongs to the first group with a relatively low incidence of IgAN, but the frequency may also vary considerably among the various population groups within the same country. For example, the incidence of IgAN among American blacks is significantly lower than that found in American whites. 14 In New Mexico (U.S.A.), the American Indian population seems to have a higher incidence of IgAN compared to Anglo and Hispanic populations. 15 In South Africa, IgAN among blacks is considerably less frequent than in the Indian population. 16 To the best of our knowledge, no specific region or ethnic group with a relatively high incidence of IgAN has been identified in Saudi Arabia. RPGN was diagnosed in 12 (4.4%) of the cases of primary glomerular disease. This is well within the 3 to 7% incidence cited in several published reports. 17 Three groups of patients with RPGN are currently recognized: approximately 20% have anti-gbm nephritis, 40% have an immune complex-mediated glomerulonephritis, and 40% have RPGN without immune deposits. 17 In our study, 9 out of 812 (75%) of the biopsy specimens revealed immune complex-mediated disease, one (8%) showed anti-gbm disease, and two (17%) had no immune deposits. Thus, there appears to be a preponderance of immune complex-induced RPGN in our series; however, since the number of cases is relatively small, no firm conclusions can be drawn. MCGN was diagnosed in 19 (10.5%) of the cases of primary glomerular disease. This is similar to the percentages reported from several other studies. Of these, 27 (93%) were classified as type I (with subendothelial deposits) while the remaining two (7%) showed features of type III MCGN (with intramembranous and subepithelial deposits). None of the specimens showed type II MCGN (dense-deposit disease). The reported frequency of type II MCGN varies from 15 to 48%. 18 Series originating from Western countries cited 450 cases of MCGN, of which 342 (76%) were type I or type III and 108 (24%) were type II In light of this, the absence of type II MCGN in our series seems very relevant. In our series, 36 specimens were from patients with systemic lupus erythematosus. The renal lesions were categorized according to WHO classification. 23 The relative frequencies of the different histological classes were similar to those reported in previously published studies. Diffuse proliferative lesions (Class IV) were the most frequent and accounted for approximately half of all cases. 24,25 Membranous nephropathy (Class V) was noted in six (16%) of the biopsies. In addition, five biopsy specimens (13.8%) revealed mixed membranous and proliferative lesions. Thus, membranous changes were present in 11 (30%) of the 36 biopsies, and this is somewhat higher than the 6 to 24% reported elsewhere for membranous nephropathy in lupus nephritis. Within the group of systemic diseases (other than lupus) involving the kidney, hemolytic uremic syndrome, Henoch-Schonlein purpura, and malignant hypertension were the most common (Table 3). Amyloidosis was noted in four cases, which represents 1.1% of all the native kidney biopsy specimens. A similarly low incidence of amyloidosis was reported in a review of renal biopsies from our institution. 3 The incidence of amyloidosis in biopsy series varies considerably among various countries in the Middle East and other regions of the world. In Jordan, Lebanon, Israel, Turkey, Tunisia, and Abu Dhabi, there is a relatively high frequency of amyloidosis, varying from 11.1 to 32.4% of all the renal biopsies. 3 This is most probably related to the prevalence of familial Mediterranean fever in these countries. 26 In other countries such as India, Germany, Sweden, and U.S.A., the incidence is much lower, varying from 1.25 to 3.3% of the biopsies. 3 Acknowledgment We would like to thank the pathologists and nephrologists in the following institutions for sending the renal biopsies to our laboratory: Riyadh Central Hospital, Riyadh Maternity and Children's Hospital, King Fahad National Guard Hospital, Riyadh, Security Forces Hospital, Riyadh, King Fahad Hospital, Al-Baha, and Al-Hada Armed Forces Hospital, Taif. References 1. Jorgensen HE, Malik GH, Paul TT, Whorra PC. Renal disease in Saudi Arabia. Ann Saudi Med 1985;5: Nielson GN, Nielson B. On the prevalence of kidney diseases in Southern Arabia. Kidney Int 1984;26: Gunibi WY, Al-Sibai B, Taher S, Akhtar M. Renal disease in Saudi Arabia: a study of 147 renal biopsies. King Faisal Specialist Hosp J 1984;4: Abdulrahman MB, Elidrissy ATH. Childhood disorders in Saudi Arabia. Pediatr Nephrol 1988;2: Lai M, Lai KN, Chan KW, et al. Pattern of glomerulonephritis in Hong Kong. Pathology 1987;19: Bodaghi E, Vazirian SB, Madani A, et al. Primary nephrotic syndrome in Iran: clinicopathologic study of 310 cases. Int J

8 Pediatr Nephrol 1986; Adu D, Amin-Addo V, Foli AK. The nephrotic syndrome in Ghana: clinical and pathological aspects. Q J Med 1981;50: Tejani A. Relapsing nephrotic syndrome. Nephron 1987;45: Tejani A. Mesangial IgM nephropathy. Nephron 1983;35: Kopolovic J, Sbvil Y, Pomeranz A, et al. IgM nephropathy: morphological study related to clinical findings. Am J Nephrol 1988;7: Gonzalo AM, Mampaso F, Gallego N, et al. Clinical significance of IgM mesangial deposits in the nephrotic syndrome. Nephron 1985;41: Vilches AR, Turner DR, Cameron JS, et al. Significance of IgM deposition in minimal change nephrotic syndrome. Lab Invest 1982;46: Micheline L, Berger J. Worldwide perspective of IgA nephropathy. Am J Kidney Dis 1988;12: Jennette JC, Wall SD, Wilkman AS. Low incidence of IgA nephropathy in blacks. Kidney Int 1985;28: Smith SM, Tung KS. Incidence of IgA-related neph-ritides in American Indians in New Mexico. Hum Pathol 1989;16: Seedat YK, Nathoo BC, Parag KB, et al. IgA nephropathy in blacks and Indians of Natal. Nephron 1988;50: Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenic mechanisms and therapy. Am J Kidney Dis 1988;11: Vargas A, Thomson KJ, Wilson D, et al. Mesangiocapillary glomerulonephritis with dense "deposits" in the basement membranes of the kidney. Clin Nephrol 1976;5: Davis AE, Schneeberger EE, Grupe WE, et al. Mem-branoproliferative glomerulonephritis (MPGN Type I) and dense deposit disease (DDD) in children. Clin Nephrol 1978;9: Habib R, Gubler M-C, Loirat C, et al. Dense deposit disease: a variant of membranoproliferative glomerulonephritis. Kidney Int 1975;7: Bohle A, Gartner HV, Fischback HM, et al. The morphological and clinical features of membranoproliferative glomerulonephritis in adults. Virchows Arch [A] 1974;363: Donadio JV Jr, Slack TK, Holley KE, et al. Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis: a clinicopathologic study. Mayo Clin Proc 1979;54: Churg J, Solein LM. Lupus nephritis. In: Chung J, Solein LM, eds. Renal disease: classification and atlas of glomerular disease. Tokyo, New York: Igaku-Shoin 1982; Cameron JS, Turner DR, Ogg CS, et al. Systemic lupus with nephritis: a long term study. Q J Med 1979;48: Lee HS, Spargo B. A renal biopsy study of lupus nephropathy in United States and Korea. Am J Kidney Dis 1985;5: Sohar E, Gafni J, Pral M, et al. Familial Mediterranean fever: a survey of 470 cases and review of the literature. Am J Med 1967;43: Verroust P, Ben-Maiz H, Morel-Maroger RL, et al. A clinical and immunopathological study of 304 cases of glomerulonephritis in Tunisia. Eur J Clin Invest 1979;9: Rahman A, Musa M, Veress B, et al. Pattern of nephrotic syndrome in Sudan. Am Trop Med Parasitol 1980;74: Sinniah R. Renal disease in Singapore with particular reference to glomerulonephritis in adults. Singapore Med J 1980;21: Prathap K, Looi LM. Morphological patterns of glomerular disease in renal biopsies from 1000 Malaysian patients. Ann Acad Med Singapore 1982;11: Cameron JS. The natural history of glomerulonephritis. In: Kincaid-Smith P, d'apices AJF, Atkins RC, eds. Progress in glomerulonephritis. New York: Wiley 1978; Sud A, Bhuyan UN, Tandon HD. Spectrum of morphological lesions in renal biopsies associated with primary nephrotic syndrome. Ind J Med Res 1978;68: Coovadia HM, Adhikari M, Morel-Maroger L. Clinico-pathological features of nephrotic syndrome in South African children. O J Med 1979;48:77-91.

9 34. Kung UA, Sitati SM. Glomerulonephropathies in Kenya: a histopathological study. East Afr Med J 1980;57: Sirivastava G, Mayekar G, Anand R, et al. Nephrotic syndrome in Indian children. Arch Dis Childhood 1975;50: International Study on Kidney Disease. Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int 1978;13: Habib R, Kleinknecht C. Primary nephrotic syndrome of childhood: classification and clinicopathologic study of 406 cases. Pathol Annual 1971;6: