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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2008  |  Volume : 19  |  Issue : 4  |  Page : 658-663
Immuno-histological Changes in Lupus Nephritis in Female Patients: A Four-Year Study


Department of Pathology, College of Medicine, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia

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   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 2019 Nov 22];19:658-63. Available from: http://www.sjkdt.org/text.asp?2008/19/4/658/41335

   Introduction Top


Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease of unknown cause showing a wide range of clinical ma­nifestations. [1],[2] Overt renal disease occurs in at least one third of SLE patients and is one of the most common severe manifestations. [2],[3],[4] 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. [5],[6],[7],[8] 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. [9] Clini­cal renal involvement ranges from asympto­matic urinary findings to the nephrotic syndrome and renal failure. [4],[6],[10],[11],[12] 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. [7] However, with the use of corticosteroids, immunosuppressive and al­kylating agents, the prognosis of these pa­tients has significantly improved over the years. [14] 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. [14]

Like many other autoimmune disorders, evidence suggests that genetic predispo­sition and environmental factors play an important role in disease expression. [4],[15] 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. [15] Immune deposits stain positive for IgG, IgM, IgA and the complement components C3, C4 and C1q on immunofluorescence. [15] Inflammatory reaction develops with me­sangial cell proliferation, expansion of me­sangial matrix and infiltration by inflamma­tory leukocytes. [10],[11] Extra-glomerular features include tubulo-interstitial nephritis. [3] 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. [10],[11],[13] 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. [16] The biopsies provide clinico-pathological correlation and prognostic information. [9],[12],[17] More recently, the usefulness of renal mor­phology, particularly in terms of activity and chronicity of the lesions on light microscopy has been noted. [13] Moreover, additional value of immunofluorescence and electron micros­copy has also been appreciated. Various morphological pictures may contribute to more appropriate choices of therapy. [18]

Occasionally, patients with LN are asymp­tomatic. [7] The general clinical complaints in­clude fatigue, fever or rash. Symptoms related to active nephritis may include peripheral edema, secondary to hypertension or hypo­albuminemia. [17] 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. [14] Mesangial lupus nephritis (WHO Class II) has an excellent prognosis while focal proliferative lupus nephritis (WHO Class III) has a good prognosis. [13]

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 Top


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 Top


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 Top


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. [14],[19],[20],[21] In a recent study carried out by JJ Khoo, [19] 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. [21],[22],[23],[24] In our study, the female to male ratio was 9.5:1, which is higher than most other series. [7],[14],[22] 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. [20] 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. [22] 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. [10],[11],[13],[17],[20],[23]

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. [22],[23],[24] 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 Top

1.Cotran RS, Kumar V, Collins T. Pathologic basis of disease: 7th ed, W.B. Saunders Company. 2005:227-35.  Back to cited text no. 1    
2.Isenberg D, Lesavre P. Lupus nephritis: assessing the evidence, considering the future. Lupus 2007;16(3):210-1.  Back to cited text no. 2    
3.Charles J, Olson J, Schwartz Msilva F. Heptinstalls pathology of the kidney. Lippincott: 5th ed, 1998:541-81.  Back to cited text no. 3    
4.Schwartz MM. The pathology of lupus nephritis. Semin Nephrol 2007;27(1):22-34.  Back to cited text no. 4    
5.Makino H, Sugiyama H, Yamasaki Y, et al. Glomerular cell apoptosis in human nephritis. Virchows Arch 2003;443(1):67-77.  Back to cited text no. 5    
6.D`Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet 2007; 369(9561):587-96.  Back to cited text no. 6    
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.  Back to cited text no. 7    
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.  Back to cited text no. 8    
9.Hurtado A, Asato C, Escudero E, et al. Clinicopathological correlations in Lupus nephritis in Lima, Peru. Nephron 1999;83 (4):323-30  Back to cited text no. 9    
10.Grande JP, Balow JE. Renal biopsy in lupus nephritis. Lupus 1998;7(9):611-7.  Back to cited text no. 10    
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.  Back to cited text no. 11    
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.  Back to cited text no. 12    
13.Fries JF, Porta J, Liang MH. Marginal benefit of renal biopsy in systemic lupus erythematosus. Arch Intern Med 1978;138 (9):1385-89.  Back to cited text no. 13    
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.  Back to cited text no. 14    
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.  Back to cited text no. 15    
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.  Back to cited text no. 16    
17.Marks SD, Sebire NJ, Pilkington C, Tullus K. Clinicopathological correlations of paediatric lupus nephritis. Pediatr Nephrol 2007;22 (1):77-83  Back to cited text no. 17    
18.Dooley MA, Falk RJ. Human clinical trials in lupus nephritis. Semin Nephrol 2007;27 (1):115-27.  Back to cited text no. 18    
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.  Back to cited text no. 19    
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.  Back to cited text no. 20    
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.  Back to cited text no. 21    
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.  Back to cited text no. 22    
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.  Back to cited text no. 23    
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.  Back to cited text no. 24    

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Correspondence Address:
Azhar Qayyum
Department of Pathology, College of Medicine, King Abdul Aziz University Hospital, P.O. Box 80205, Jeddah 21589
Saudi Arabia
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