| Abstract|| |
Identification of the profile of glomerular disease in a particular geographical region is of fundamental academic, clinical and epidemiological importance. It helps in the recognition of specific risk factors and subsequent planning for adequate prevention. In the present study, 1234 consecutive renal biopsies referred to the nephropathology team of Cairo University over two years were retrospectively analyzed. The main indications for biopsy included nephrotic syndrome, persistent sub-nephrotic proteinuria, recurrent hematuria, suspected secondary hypertension, lupus nephritis and acute and chronic renal failure of undetermined etiology. Proliferative forms of glomerulonephritis [GN] (32.1%) and focal and segmental glomerulosclerosis [FSGS] were the most prevalent lesions among patients with the nephrotic syndrome (22.6%). In subjects with subnephrotic proteinuria, FSGS was the principal lesion followed by proliferative lesions. Although all forms of GN were encountered in those presenting with recurrent hematuria, mesangioproliferative GN and FSGS were significantly more frequent. IgA glomerular deposits were detected in 9.8% of all GNs and 15% of those presenting with hematuria. One half of the biopsies obtained for the assessment of suspected secondary hypertension showed only changes compatible with the effect of hypertension per se, i.e. nephroangiosclerosis. On the other hand, a parenchymal renal lesion was found in 52.9% of biopsies. The common glomerular pathologies in patients with lupus nephritis were Classes III and IV. Among patients with chronic renal failure, the predominant lesion was chronic interstitial nephritis (32.6%). An acute interstitial inflammatory element was also detected in 8.4% of cases. About one third of the biopsies obtained for acute renal failure showed acute tubular (11%) or cortical (13.2%) necrosis. Another third showed vasculitis (17.6%) or acute interstitial nephritis (14.3%), and the remaining showed chronic lesions in which the rapid deterioration was probably functional.
Keywords: Glomerulonephritis, Egypt, Nephrotic syndrome, Hematuria, Acute renal failure, Chronic renal failure.
|How to cite this article:|
Barsoum RS, Francis MR. Spectrum of Glomerulonephritis in Egypt. Saudi J Kidney Dis Transpl 2000;11:421-9
| Introduction|| |
Glomerulonephritis [GN] remains as a major cause of morbidity and mortality from renal disease in many parts of the world, particularly in the tropical and subtropical regions. According to several local registries and sporadic publications, it seems to be responsible for 23.2 to 58.4% of patients on regular dialysis in the tropics, ,, compared to contemporary figures of around 16-18% in the United States  and 9-15% in Europe.  Its prevalence among dialysis patients in Egypt has been reported as 16.6% in 1998. 
Secondary forms of GN are much more common in the tropics than in the industrialized countries.  The major primary cause is infection.  Some of the infective agents have been identified, such as Streptococcus, schistosomiasis and malaria. Others are only speculative, being suspected from the strikingly high prevalence of proliferative GN, the prototype lesion of such etiology.
Etiology is not the only difference between tropical and non-tropical GN. Racial factors seem to play an important role, not only in influencing incidence, but also in defining the pattern, severity and progression of the glomerular response.  Environmental factors may also be involved as modifiers of the glomerular pathology in different geographical regions. Of particular interest is the role of heavy metal  and hydrocarbon  pollution, the epidemiological significance of which remains to be elucidated.
For these reasons, it is of considerable interest to identify the patterns of glomerular disease in specific regions. In this paper, we review the prevalence of different forms of GN in Egypt, based on retrospective analysis of renal biopsies obtained over a 2-year period.
| Materials and Methods|| |
All percutaneous renal biopsies for medical renal disease submitted to the nephropathology unit of Cairo University from January 1998 to December 1999 are included. These had been obtained from patients presenting to the University hospitals or referred from other renal units mostly in the Greater Cairo area.
Biopsy cores had been processed according to the standard techniques; paraffin sections were produced and stained with hematoxylin and eosin, periodic acid schiff and Massontrichrome stains and examined by light micros-copy. Whenever necessary, sections had also been stained with silvermethenamine or congo-red. When requested, immunofluo-rescence studies had been made either on cryostat or paraffin sections using immuno-peroxidase. Electron microscopy had been performed only occasionally, when the data obtained by light microscopy and immuno-fluorescence were not sufficiently informative.
A total of 1234 biopsies were thus included in the study, 578 obtained during 1998 and 656 during 1999. Of these 667 had been obtained from male subjects and 567 from females. The age-range was 1 to 85 years with a mean of 30.5 + 17.4 years, without significant difference between genders. The indications for renal biopsy, as obtained from the histopathology request forms, were used for the categorization of data, which were statistically analyzed using a standard chi-square test.
| Results|| |
[Table - 1] shows the categories of biopsies included in the study based on the indication for biopsy. There were significantly more males in the nephrotic and hypertension groups and more females with lupus nephritis. Those in the hypertension and chronic renal failure groups were significantly older than the others. There were no significant differences in the mean age between males and females within any category .
The Nephrotic syndrome
The frequency of different histopathological lesions in nephrotic patients is shown in [Table - 2]. Focal and segmental glomerulosclerosis [FSGS] was the most frequent pathology encountered. Excluding minimal change disease, the next in frequency was proliferative forms of GN. Mesangial IgA deposits were detected in 8% of renal biopsies in this category.
FSGS was again the most frequently encountered lesion, followed by proliferative lesions [Table - 3]. IgA deposits were observed in 9.5% of cases in this group.
Compared to the profile observed in patients with the nephrotic syndrome [Figure - 1], there was a significantly higher prevalence of focal proliferative and diffuse mesangial proliferative glomerulonephritides and a lower frequency of minimal change disease, membranous nephropathy and amyloidosis.
The spectrum of histopathological lesions in patients with microhematuria was very wide, including most forms of GN. Proliferative lesions and FSGS were still the most common lesions [Figure - 2]. Mesangial IgA deposits, compatible with IgA nephropathy, were detected in a minority of cases, varying between 15.4% among patients with mesangioproliferative GN to 40% among those with focal proliferative GN [Figure - 2]. However, IgA deposits were detected in all cases presenting with gross hematuria.
Nephro-angiosclerosis was the most common lesion encountered in this category and occurred with the highest frequency compared to others (p < .0001). The frequency of occurrence of various forms of GN was not significantly different from the profile obtained in patients with subnephrotic proteinuria or microhematuria [Table - 4].
Evaluation of Lupus Nephritis
The policy of all referring units was to obtain a renal biopsy from all patients with SLE having evidence of renal involvement. While our policy was to categorize the histopathological lesions according to the WHO classification, overlapping patterns were often identified. Those cases were categorized under the higher class. The histological profile thus generated is shown in [Figure - 3].
Chronic renal failure
Chronic interstitial nephritis was the lesion most frequently encountered in this category. Acute interstitial nephritis was also seen superimposed on other lesions in 8.4% of cases. In 10.7% of cases, the kidney was badly damaged, hence it was impossible to distinguish a primary pattern. The frequency of different histological patterns is shown in [Table - 5].
Acute renal failure
Acute renal failure was defined as a rapid deterioration of renal function in an otherwise apparently healthy individual or a patient with chronic renal disease. Renal biopsy was obtained when circumstantial and clinical data did not reveal an acute factor, or when recovery was delayed beyond the expected duration. The frequency of different histological patterns is shown in [Table - 6].
| Discussion|| |
In order to outline the prevalence of different glomerular diseases among patients presenting to specialized Egyptian renal centers in the Greater Cairo area, a total of 1234 renal biopsies, pooled into the same laboratory and examined by the same team, were analyzed according to the reported clinical indications for biopsy. Surgical and autopsy materials were excluded.
There were seven main indications for biopsy: i) nephrotic syndrome in adults or steroid-resistant or -dependent nephrotic syndrome in children (31.9%); ii) persistent sub-nephrotic proteinuria of more than 1 gm/24 hours (22.5%); iii) recurrent hematuria after the exclusion of urological causes (3.2%); iv) suspected secondary hypertension after exclusion of renovascular disease (1.4%); v) assessment of serologically confirmed systemic lupus erythematosus with renal involvement (12%); vi) chronic renal disease of unidentified etiology, particularly when associated with preservation of renal size (21.2%) and vii) acute renal failure including rapid deterioration of function in patients with previously stable chronic renal disease (7.4%).
The pattern of glomerular disease in nephrotic subjects was strikingly different from that reported in the West,  although matching with reports from other developing countries.  The outstanding feature was the high prevalence of different forms of proliferative GN, which suggests an important pathogenetic role of infection or environmental pollution. Next in frequency was FSGS, which seems to be the preferential glomerular response in this part of the world, even to the same antigen. A notable example is schistosomal nephropathy, in which Africans often develop FSGS while Latin Americans develop a mesangioproliferative lesion.  FSGS is also known to be notoriously common among the Blacks, compared to other ethnic populations in the United States. 
The pattern in sub-nephrotic proteinuria was broadly similar, yet with significant quantitative differences. While minimal change disease, membranous nephropathy and amyloidosis were more common in nephrotics, focal and diffuse mesangial proliferative GNs were more frequent in those with sub-nephrotic proteinuria. This is not surprising in view of the nature of glomerular injury in the respective patterns. It is notable, though, that FSGS and mesangiocapillary [membranoproliferative] GN [MCGN] were found with similar frequency in both categories, confirming that functional factors, rather than histological patterns, are more important in defining the extent of proteinuria and hence the development of the nephrotic state. 
Recurrent hematuria was the indication for biopsy in a minority (3.24%) of cases, which reflects the infrequency of IgA nephropathy in Africa, accounting for 2.4% of all GNs in South Africa,  3.8% in Tunisia,  and 4.9% in previous reports from Egypt.  In the present series, IgA deposits were detected in 9.8% of all non-lupus GNs, amounting to 15% of those presenting with microhematuria. This is in sharp contrast to the high prevalence of this disease in the Asia-Pacific region where it accounts for one third to one half of all cases of primary GNs. , It is suggested that genetic factors may play an important role in generating this difference in primary IgA nephropathy.  In contrast, secondary IgA nephropathy has been reported as the hallmark of progressive renal involvement in hepatosplenic schistosomiasis in Egypt.  It is interesting that none of the biopsies included in this series showed this lesion perhaps reflecting the clinical policy of not subjecting such patients to an invasive procedure without significant reflection on diagnosis or treatment.
Renal biopsy had been obtained from only 17 patients with suspected secondary hypertension, usually because of relatively young age at onset (mean 30.0 years in males and 34.8 years in females) or the presence of significant proteinuria. This was rewarded by the detection of an intrinsic renal parenchymal disease in more than half of the cases. Indeed, very unexpected pathology was often identified, such as vasculitis or amyloidosis. In the remaining half, the diagnosis was probably essential hypertension with secondary nephro-angiosclerosis.
The renal histopathological findings in lupus nephritis were broadly similar to those reported in other series,  apart from the strikingly high frequency of class III. In contrast to all other classes, males predominated in class III for reasons that are not very clear.
The large number of biopsies obtained from patients with chronic renal failure reflects the increasing interest in identifying the nature of the underlying renal disease, even in patients needing renal replacement therapy. In addition to epidemiological reflections, this trend is useful in increasing the awareness of the risk of recurrence of certain primary diseases in transplanted kidneys. It was quite rewarding to be able to make a firm diagnosis of the primary disease in about 90% of cases. Strikingly, the most common pathology was interstitial, which conforms to previous reports.  This observation is often taken as an indication of a significant role of environmental pollution in the high prevalence of chronic renal failure in Egypt.
Of the various forms of GN, those most often associated with chronic renal failure in this series were FSGS and MCGN. Those least frequently encountered were focal proliferative GN and nodular glomerulo-sclerosis. The latter was most often encoun-tered in diabetics. Its relative infrequency in this, as well as in all other categories, reflects the clinical policy of not subjecting diabetics with renal disease to renal biopsy unless there is good reason to question the causal relationship in a particular patient.
Renal biopsy was an extremely valuable diagnostic tool in patients with acute renal failure in whom the clinical course was atypical. The relative infrequency of acute tubular necrosis is obviously due to selection bias, since most of these patients are not subjected to biopsy. The 11% prevalence in this series represents those with prolonged oliguria or, even more often, those with suspected drug-induced acute renal failure. The diagnosis of acute cortical necrosis in as many as 13.2% of biopsies on the other hand, is a positive selection of those with persistent acute renal failure following conventional insults as pregnancy complications, systemic inflammatory response syndrome, severe sepsis, etc.
Vasculitis and acute interstitial nephritis were responsible for one third of acute renal failures in this series. This reflects the general trend of increased incidence of vasculitis world-wide, Egypt not being an exception. Most of the acute interstitial nephritides eventually turned out to be drug-induced, again emphasizing the growing importance of iatrogenic renal disease.
In the remaining third of patients, the biopsy diagnosis pointed to a pre-existing chronic glomerular or tubulointerstitial disease. Acute deterioration seems to have occurred as a result of fluid or electrolyte depletion, or to the administration of a potentially nephrotoxic agent that induced functional rather than structural derangement, e.g. angiotensin-converting enzyme inhibitors, diuretics or non-steroidal anti-inflammatory agents.
| Acknowledgements|| |
The authors wish to acknowledge the following medical centers that referred their biopsy material included in this study: Ahmed Maher Teaching Hospital, Ain Shams University Hospitals, Air Forces Hospital, Al Azhar University Hospitals, Al Salam Hospital (Mohandessin), Al Ziraeyeen Hospital, Arab Contractors' Medical Center, Arab Organization For Industries Hospital, As-Salam International Hospital, Cairo Kidney Center, Dar El Fouad Hospital, Egyptair Hospital, El Marwa Hospital, El Taiseer Hospital Mansoura, Fayrouz Hospital, Giza Renal Center, Ibn Sina Hospital, Italian Hospital, International Hospital for Urology & Nephrology, Islamic Charitable Organization Hospital, (Agouza), Magdi Soliman Hospital, Mahmoud Mosque Hospital, Military Hospital (El Gallaa), Military Hospital (Kobry El Koba), Military Hospital (Meadi), Misr Elgadeda Nephrology Center, Misr Kidney Center, Misr International Hospital, Nasser Institute, Nasr City Hospital, National Institute for Nephrology & Urology, Nile Badrawy Hospital, Nile International Kidney Center, Nozha International Hospital, Petrol Workers Medical Center, Police Hospital, Theodor Bilharz Institute, Zagazig University Hospitals as well as individual physicians from Alexandria, Cairo, Ismailia, Mansoura, Shebeen El Kom, Tanta and Suez.
They also thank Dr. Wessam Ismaiil from the Kasr-Aini Nephrology and Dialysis Center for helping in collecting and tabulating the data.
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Rashad S Barsoum
The Cairo Kidney Center, P.O. Box 91, Bab-El-Louk, Cairo 11513
[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6]