| Abstract|| |
The objective of this study was to classify renal biopsies of all female patients diagnosed to have systemic lupus erythematosus at the College of Medicine, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia over a period of four years between 19th January 2002 and 30th April 2006. Lupus nephritis was classified according to the modified WHO classification. The immunofluorescence pattern was also studied. All the study patients were examined, investigated, treated and followed-up in our center. We observed that class IV lupus nephritis was the most commonly seen lesion and IgG showed strong positivity in most of the cases. We believe that a more elaborate study is needed to explain the relatively high female to male ratio noticed in our study.
Keywords: Systemic lupus erythematosus, Lupus nephritis, Renal biopsy
|How to cite this article:|
Qayyum A, Nagy AA. Immuno-histological Changes in Lupus Nephritis in Female Patients: A Four-Year Study. Saudi J Kidney Dis Transpl 2008;19:658-63
|How to cite this URL:|
Qayyum A, Nagy AA. Immuno-histological Changes in Lupus Nephritis in Female Patients: A Four-Year Study. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2023 Feb 9];19:658-63. Available from: https://www.sjkdt.org/text.asp?2008/19/4/658/41335
| Introduction|| |
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease of unknown cause showing a wide range of clinical manifestations. , Overt renal disease occurs in at least one third of SLE patients and is one of the most common severe manifestations. ,, It is one of the eleven diagnostic criteria proposed by the American College of Rheumatology, four of which are required to support a diagnosis of SLE. ,,, The patients have urinary or renal function abnormalities early in the course of the disease. In 90% of these patients, renal disease occurs within two to five years from disease onset.  Clinical renal involvement ranges from asymptomatic urinary findings to the nephrotic syndrome and renal failure. ,,,, Development of nephritis in SLE patients is closely linked to survival and morbidity. A good number of patients reach end-stage renal failure within 10 years.  However, with the use of corticosteroids, immunosuppressive and alkylating agents, the prognosis of these patients has significantly improved over the years.  Despite this, considerable variation remains depending on many factors including response to corticosteroids and immunosuppressive therapy because their toxicity also contributes in morbidity and mortality. 
Like many other autoimmune disorders, evidence suggests that genetic predisposition and environmental factors play an important role in disease expression. , Autoimmunity has a major part to play in the pathogenesis of lupus nephritis (LN). The immunological mechanisms include presentation of antibodies directed against nuclear elements. These antibodies form pathogenic immune complexes. In the kidneys, deposition of the immune deposits initiates an inflammatory response by activating the complement cascade and recruiting inflammatory cells that can subsequently be observed on biopsy specimens.  Immune deposits stain positive for IgG, IgM, IgA and the complement components C3, C4 and C1q on immunofluorescence.  Inflammatory reaction develops with mesangial cell proliferation, expansion of mesangial matrix and infiltration by inflammatory leukocytes. , Extra-glomerular features include tubulo-interstitial nephritis.  Because of the varied presentation, renal biopsy evaluation may be used to confirm the diagnosis, to evaluate disease activity, to determine prognosis and to determine appropriate therapy. ,, Transformation to a more severe or less severe histologic class is well documented and may result from treatment or be a part of the natural history of the disease.  The biopsies provide clinico-pathological correlation and prognostic information. ,, More recently, the usefulness of renal morphology, particularly in terms of activity and chronicity of the lesions on light microscopy has been noted.  Moreover, additional value of immunofluorescence and electron microscopy has also been appreciated. Various morphological pictures may contribute to more appropriate choices of therapy. 
Occasionally, patients with LN are asymptomatic.  The general clinical complaints include fatigue, fever or rash. Symptoms related to active nephritis may include peripheral edema, secondary to hypertension or hypoalbuminemia.  Poor prognostic indicators include delay in treatment, young age at onset of nephritis, male sex, hypertension, nephritic syndrome and renal biopsy finding of diffuse prolifrative glomerulonephritis or high chronicity index.  Mesangial lupus nephritis (WHO Class II) has an excellent prognosis while focal proliferative lupus nephritis (WHO Class III) has a good prognosis. 
The objective of this study was to classify renal biopsies of all female patients with LN who were seen in the College of Medicine, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia over a period of four years between 19th January 2002 and 30th April 2006. Classification of LN was according to the modified WHO classification, using facilities of light, fluourescent and electron microscopy. The other objective was to observe the immunological pattern. We hope that this study will not only show a pattern of this disease in our area but will also be a source of comparison for other researchers.
| Materials and Methods|| |
Renal biopsies taken from our female patients during the period from 19th January 2002 to 30th April 2006 were reviewed. All the study patients were investigated, treated and followed-up at the King Abdul Aziz University Hospital in Jeddah. Patients with renal complaints, either at the time of diagnosis at initial presentation or during follow-up, underwent renal biopsy. Percutaneous renal biopsies were performed under ultrasound guidance by nephrologists. The biopsy material was fixed in 10% formalin, later dehydrated in ascending grades of series of ethanol, cleared in xylene and embedded in paraffin. Sections of 5 um were obtained with a standard microtome and mounted on glass slides. All biopsy slides were stained with hematoxylin-eosin, PAS, trichrome, GMS and Congo red stains for light microscopy. Fresh renal tissues received were submitted for immunofluorescence studies. Only biopsies containing five or more glomeruli were considered adequate for classification.
A total of 38 renal biopsies were found to be appropriate for the study. Of these, 34 biopsies were from females with SLE while the other four were from males. Only female cases were studied. Reports of immunofluorescence for IgG, IgM, IgA, C3, C4, C1q and fibrinogen were considered along with electron microscopy reports. All biopsies were classified according to the modified WHO classification into six classes, i.e. normal, mesangial, focal segmental, diffuse proliferative, membranous and advanced sclerosis. Within each class the sub-groups were also noted. The classification was done on the basis of the most prominent lesion. A lesion was considered active if there were cellular infiltrates, karyorrhexis, cellular crescents, fibrinoid necrosis, vasculitis and interstitial inflammatory infiltrate. Chronicity was judged by glomerular sclerosis and interstitial fibrosis.
| Results|| |
Four biopsies demonstrated pure mesangial changes (Class II). In three of them, there was mesangial widening (Class IIA) while in one, moderate hypercellularity was noted (IIB). Focal lesions (Class III) were seen in three patients. These were not further subclassified. Nineteen patients had diffuse proliferative glomerulonephritis (Class IV). Of them, 16 had necrotizing lesions (Class IVB) while three had glomerular sclerosis in addition to active lesions (Class IVC). Membranous lesions were seen in eight patients. Pure membranous lesions (Class VA) were not seen. All membranous lesions were seen in association with other glomerular lesions (Class VB). None of the study patients had advanced glomerular sclerosis (Class VI) or modified WHO class I lesion. Active lesions occurred primarily among patients with class IV disease. In addition to the active necrotizing lesions, these patients had cellular crescents, karyorrhexis and interstitial inflammation [Table 1].
Immunofluorescence could not be performed in three cases. Out of the remaining 34 cases, results of 31 biopsies have been depicted in [Table 2]. IgG showed strong positivity in most of the cases (22) and it was negative in only one case. On the other hand, fibrinogen was mostly negative (28), was moderately positive in two cases and weakly positive in one. IgA was weakly positive in 13 cases. IgM was moderately positive in 17 cases. C3 was strongly positive in 15 cases while C4 showed mostly weak positivity in 14 cases while C1q was negative in most of the cases (17cases) [Table 2].
| Discussion|| |
In our study, the youngest age at presentation was six years. One female patient developed the disease at nine years of age. Most of the other cases presented in the age range of 17 to 28 years. Only one female presented at 61 years of age, which is an exception. Lupus nephritis usually presents after the age of 10 years and rarely before five years. ,,, In a recent study carried out by JJ Khoo,  85.2% children presented with LN after the age of ten years. Thus, the age range of our cases is more or less in accordance with other recent studies.
Lupus nephritis is more common in females as compared to males. ,,, In our study, the female to male ratio was 9.5:1, which is higher than most other series. ,, The reason behind this unusually high ratio is unclear. Same observation has been reported in a study carried out in Thailand in which the ratio was 19:1.  A previous report from Thailand, showed a ratio close to that reported in the United States and the United Kingdom of 10:1 but the combined figures show a ratio of 14:1.  One possible explanation for the high ratio in our series is that there are large number of consanguinous marriages in Saudi society. This can also be due to a relatively smaller number of cases in our study or may be reflecting a pattern of renal disease in this area.
We observed that class IV LN was the most common class with 19 of 34 female cases showing this lesion. This finding has also been previously reported in many other series. ,,,,,
Majority of our patients with mesangial lesions had some clinical evidence of renal disease, including elevated serum creatinine levels. One patient with class III lesion had no clinical evidence of renal disease but had significant findings on biopsy. Although it was an exception, we believe that biopsy certainly helps to identify patients at risk of developing progressive renal disease. ,, We conclude that although our study was quite limited, it generally showed the same histological and immunological pattern as observed by other authors. However, we feel that a more elaborate study is needed to explain some variations seen in our study.
| References|| |
|1.||Cotran RS, Kumar V, Collins T. Pathologic basis of disease: 7th ed, W.B. Saunders Company. 2005:227-35. |
|2.||Isenberg D, Lesavre P. Lupus nephritis: assessing the evidence, considering the future. Lupus 2007;16(3):210-1. |
|3.||Charles J, Olson J, Schwartz Msilva F. Heptinstalls pathology of the kidney. Lippincott: 5th ed, 1998:541-81. |
|4.||Schwartz MM. The pathology of lupus nephritis. Semin Nephrol 2007;27(1):22-34. |
|5.||Makino H, Sugiyama H, Yamasaki Y, et al. Glomerular cell apoptosis in human nephritis. Virchows Arch 2003;443(1):67-77. |
|6.||D`Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet 2007; 369(9561):587-96. |
|7.||Mak A, Mok CC, Chu WP, To CH, Wong SN, Au TC. Renal damage in systemic lupus erythematosus: a comparative analysis of different age groups. Lupus 2007;16(1):28-34. |
|8.||Korbet SM, Schwartz MM, Evans J, Lewis EJ, Collaborative Study Group. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol 2007;18(1):244-54. |
|9.||Hurtado A, Asato C, Escudero E, et al. Clinicopathological correlations in Lupus nephritis in Lima, Peru. Nephron 1999;83 (4):323-30 |
|10.||Grande JP, Balow JE. Renal biopsy in lupus nephritis. Lupus 1998;7(9):611-7. |
|11.||Shin JH, Pyo HJ, Kwon YJ, et al. Renal biopsy in elderly patients: clinicopathological correlation in 117 Korean patients. Clin Nephrol 2001;56(1):19-26. |
|12.||Zappitelli M, Duffy C, Bernard C, et al. Clinicopathological study of the WHO classification in child-hood lupus nephritis. Pediatr Naphrol 2004;19(5):503-10. |
|13.||Fries JF, Porta J, Liang MH. Marginal benefit of renal biopsy in systemic lupus erythematosus. Arch Intern Med 1978;138 (9):1385-89. |
|14.||Emre S, Bilge I, Sirin A, et al. Lupus nephritis in children: prognostic significance of clinico-pathological findings. Nephron 2001;87(2):118-26. |
|15.||Brugos B, Kiss E, Szodoray P, Szegedi G, Zeher M. Retrospective analysis of patients with lupus nephritis: Data from a large clinical immunological center in Hungary. Scand J Immunol 2006;64(4):433-7. |
|16.||Patel M, Clarke AM, Bruce IN, Symmons DP. The prevalence and incidence of biopsyproven lupus nephritis in the UK: evidence of an ethnic gradient. Arthritis Rheum 2006;54(9):2963-9. |
|17.||Marks SD, Sebire NJ, Pilkington C, Tullus K. Clinicopathological correlations of paediatric lupus nephritis. Pediatr Nephrol 2007;22 (1):77-83 |
|18.||Dooley MA, Falk RJ. Human clinical trials in lupus nephritis. Semin Nephrol 2007;27 (1):115-27. |
|19.||Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK. Lupus nephritis in children in Malaysia. J Pediatr Child Health 2005;41 (1-2):31. |
|20.||Supavekin S, Chatchomchuan W, Pattaragarn A, Suntornpoch V, Sumboonnanonda A. Pediatric systemic erythematosus in Sirraj Hospital. J Med Assoc Thai 2005;88 (Suppl8):S115-23. |
|21.||Bogdanovic R, Nikolic V, Pasic S, et al. Lupus nephritis in childhood: a review of 53 patients followed at a single center. Pediatr Nephrol 2004;19(1):36-44. |
|22.||Wong SN, Tse KC, Lee TL, Lee KW, et al. Lupus nephritis in Chinese children: a territory-wide cohort study in Hong Kong. Pediatr Nephrol 2006;21(8):1104-12. |
|23.||Flower C, Hennis A, Hambleton IR, Nicholson G. Lupus nephritis in an AfroCaribbean population: renal indices and clinical outcomes. Lupus 2006;15(10):689-94. |
|24.||Singh S, Devidayal, Minz R, Nada R, Joshi K. Childhood lupus nephritis: 12 years experience from North India. Rheumatol Int 2006;26(7):604-7. |
Department of Pathology, College of Medicine, King Abdul Aziz University Hospital, P.O. Box 80205, Jeddah 21589
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]