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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 727-732
Poor prognostic factors of lupus nephritis


1 Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
2 Department of Immunology, Hedi Chaker Hospital, Sfax, Tunisia
3 Anatomopathology Department, Habib Bourguiba Hospital, Sfax, Tunisia
4 Department of Internal Medicine, Hedi Chaker Hospital, Sfax, Tunisia

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Date of Web Publication9-Jul-2011
 

   Abstract 

The occurrence of renal involvement during the clinical course of systemic lupus erythematous (SLE) is generally considered to be the most important factor influencing the prognosis in terms of morbidity and mortality. The factors influencing prognosis in lupus nephritis (LN) are variable in literature. Our aim was to determine predictive factors of poor prognosis in LN among our population. In this retrospective study, 82 cases of LN observed over 18 years were studied. There were 12 males and 70 females with a mean age of 26.9 ± 11 years. At presentation, the mean proteinuria was 3.9 ± 4 g/day; the nephrotic syndrome, hematuria, leukocyturia and renal failure were observed in 67.1%, 63.4%, 56.1% and 37.8% of cases, respectively. LN was of class I, II, III, IV and V in 4.9%, 13.4%, 23.2%, 50% and 8.5% of the cases, respectively. Fifteen patients developed end-stage renal failure and/or died. The presence of hypertension, renal failure, massive proteinuria and high activity index score of LN was associated with poor renal prognosis.

How to cite this article:
Kammoun K, Jarraya F, Bouhamed L, Kharrat M, Makni S, Hmida MB, Makni H, Kaddour N, Boudawara T, Bahloul Z, Hachicha J. Poor prognostic factors of lupus nephritis. Saudi J Kidney Dis Transpl 2011;22:727-32

How to cite this URL:
Kammoun K, Jarraya F, Bouhamed L, Kharrat M, Makni S, Hmida MB, Makni H, Kaddour N, Boudawara T, Bahloul Z, Hachicha J. Poor prognostic factors of lupus nephritis. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Jul 19];22:727-32. Available from: http://www.sjkdt.org/text.asp?2011/22/4/727/82660

   Introduction Top


Lupus nephritis (LN) is generally considered as the major cause of morbidity and mortality in the course of systemic lupus erythematous (SLE). [1],[2] Renal involvement in lupus is frequent in Tunisia. Houman et al reported that LN occurs in 43% of patients with SLE. This frequency is higher than that observed in Europe, but is comparable to the frequency in Africans and African Americans. [1],[2],[3] Although the prognosis of LN has improved in the past few decades in industrialized countries, [4] the outlook in developing countries is less optimistic. [1],[2] This may be attributed to social, environmental and genetic factors. [5]

Many studies have been conducted to identify the predictors of poor prognosis in patients with LN, but results are different and sometimes conflicting. Little is known about the outcome and prognosis factors of LN in Tunisia.

The aim of the present retrospective study was to identify the clinical, biological and histological factors determined at the time of renal biopsy, which could represent prognostic factors for LN in the south of Tunisia.


   Subjects and Methods Top


We retrospectively studied all patients with LN confirmed by kidney biopsy performed in the Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia. All patients fulfilled four or more criteria for the diagnosis of LN as defined by the American College of Rheumatology. [6] The evidence of LN included abnormal urinalysis and/or elevated serum creatinine level. Abnormal urinalysis was considered when the 24-hour protein excretion was equal to or greater than 0.5 g/24 hours and/or there were 10,000 red cells or white cells/mL on Addis's count. Percutaneous renal biopsy was performed in all patients. The specimens were processed for light microscopy and immuno-fluorescence.

An adequate biopsy specimen contained at least five glomeruli. Renal lesions were classified according to the ISN classification. [7] Screening for activity index (AI) and chronicity index (CI) was done using the parameters according to the National Institute of Help Group Report. [8]

Definitions

Complete remission was defined as 24-hour proteinuria <1 g/24 hours with absence of hematuria, and serum creatinine concentration of <120 μmol/L. Partial remission was defined as 24-hour proteinuria between 1 g and 2 g/24 hours and serum creatinine of <120 μmol/L. Lack of remission was considered when proteinuria was >2 g/24 hours and/or the serum creatinine concentration was >120 μmol/L. Relapse was defined as reappearance of proteinuria >1 g/24 hours or increase in proteinuria by >50% and/or occurrence of acute renal failure. Poor out-come was defined as death or occurrence of end-stage renal failure (ESRF).


   Statistical Analysis Top


Data analyses were performed using SPSS 11.0. Results were given as mean ± SD. Student's t-test and Chi square were used to calculate P value. P values less than 0.05 were considered statistically significant.


   Results Top


Eighty-two patients with LN (12 males and 70 females) were included in this study. The most common extra-renal manifestations seen in our patients were anemia, articular and mucocutaneous manifestations [Table 1]. The baseline proteinuria was 3.9 ± 4 g/24 hours (0-26 g/24 hours). The nephrotic syndrome was present in 55 cases at presentation, and hematuria and leukocyturia were observed in 52 cases (63.4%) and 46 cases (56.1%), respectively. The mean serum creatinine concentration was 153 ± 146 μmol/L. Thirty-one cases (37.8%) had impaired renal function. Eleven patients had serum creatinine levels above 200 μmol/L.
Table 1: Frequency of occurrence of extra-renal manifestations in the study patients.

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Antinuclear antibodies were positive in 80 cases. Anti-DNA antibodies were positive in 50 cases. The relative frequency for each class of LN was as follows: Class I: four cases (4.9%); Class II: 11 cases (13.4%); Class III: 19 cases (23.2%); Class IV: 41 cases (50%); and Class V: seven cases (8.5%).

Fifty-three patients (64.6%) were treated with corticosteroids, and 29 patients (35.4%) received corticosteroids and cyclophosphamide. Patients who received corticosteroids alone included four with Class I LN, 11 with Class II, 17 with Class III and 14 patients with class IV LN. Patients who received cyclophosphamide in addition, included two with Class III LN and 27 with Class IV LN.

The mean duration of follow-up was 83 ± 58 months. The renal survival rates at one year, five years and 10 years were 92.7%; 84.1%; and 76.8%, respectively.

Twelve patients died and 15 patients developed ESRF. For comparison, the study patients were divided into two groups. Group I (G-I) represented patients who died and/or developed ESRF (n = 15 patients), while group II (G-II) represented patients who survived and had not developed ESRF at last follow-up.

Comparison between the two groups did not reveal any difference in age, gender, or duration of lupus before the occurrence of renal manifestations.

Among the clinical characteristics at presentation, presence of hypertension and especially high systolic pressure predicted poor prognosis. Similarly, proteinuria above 3 g/24 hours, impaired renal function at presentation and presence of hematuria and leukocyturia indicated poor prognosis.

Hypo-complementemia was observed more frequently in G-I patients, although this difference was not statistically significant [Table 2]. Patients with Class III or IV LN at initial biopsy were associated with a more aggressive course. Crescentic proliferation affecting more than 30% of the glomeruli and/or the presence of severe or moderate interstitial infiltration were poor prognostic factors.
Table 2: The principal epidemiological, clinical and histological factors in the two groups of patients with systemic lupus nephritis (n = 82).

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There was no difference in the prevalence of other active glomerular lesions (endocapillary proliferation, karyorrhexis, fibrinoid necrosis, wire loop) between the two groups. Interstitial fibrosis was more frequent in the group with poor renal outcome. The mean AI was 6.3 ± 3.4. It was significantly higher in G-I. The mean CI was 0.9 ± 1, which was higher in the poor prognosis group, although the difference was not significant. Similarly, a sclerosis index was ≥3 and was more frequently seen in G-I, although the difference was not significant [Table 3].
Table 3: Principal histological features of the study patients.

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Remission was achieved more frequently in patients in G-I. The number of flares was also significantly higher in the group with ESRF [Table 2].


   Discussion Top


In this study, we analyzed the baseline predictive factors of evolution to ESRF in patients with LN. The factors studied included impaired renal functions, massive proteinuria, hypertension, high AI and interstitial fibrosis. Failure to obtain remission and occurrence of frequent relapses were predictive of poor prognosis.

Demographic factors such as age and sex have emerged as important prognostic indicators in some, but not all previous studies. Young age at onset of nephritis has been described as a poor prognosis factor. [9] Also, male gender has been considered by some authors as a risk factor for poor renal survival. [9] Moroni et al have shown that male sex is predictive of therapeutic resistance and reduction of renal survival. [10] Our results show that survival was unaffected by age and sex.

Clinical and biological predictors of poor renal outcome in LN have been well described in previous studies. Presence of massive proteinuria, the nephrotic syndrome, impaired renal function, hypertension and hypo-complementemia have been associated with poor prognosis. [8],[11],[12],[13],[14],[15],[16],[17] Our results corroborate these findings.

Faurshow et al have reported that serum creatinine above 140 μmol/L increased the risk for ESRF by 3.5. [18] Martins et al have shown that hypertension is a risk factor for chronic renal failure and that initial acute renal failure is associated with greater risk for death or ESRF. [19]

The present study confirms the prognostic importance of renal histological evaluation in patients with LN. However, our results are in only partial agreement with previous studies. Class III and IV LN are associated with a more aggressive course, with faster deterioration in renal function than the other classes. [2],[3],[12],[14],[16],[18],[20] The histological activity and chronicity indices provide semi-quantitative information regarding the severity of acute and chronic injury to different components of kidney in LN (glomerular, tubular, and vascular injury). A high AI has been shown to predict poor renal and patient prognosis in most studies. [17],[21] However, other studies failed to demonstrate a relationship between AI and the course of LN. [19] Other studies have shown that a combined activity and chronicity indices has a strong predictive value in the course of LN. [22] In our study, the AI was higher in patients who developed ESRF or died. However, the CI was not predictive of ESRF. This lack of correlation could be attributed to the relatively low CI in most patients in our study.

Nossent observed that a CI greater than three was predictive of poor renal and patient out-come. [20] Similar conclusion was drawn by other studies. [15] The CI as well as all of its components may reflect late diagnosis or previous silent LN. Nossent has noted that a high CI was associated with poor renal and patient survival, but they found no correlation between the duration from the onset of clinical LN and severity of chronic lesions seen on biopsy. However, they found high chronicity score in patients who had a biopsy performed early after the occurrence of clinical renal involvement. This would suggest the presence of preexisting clinical silent renal disease. [20] Among the different chronic lesions, interstitial fibrosis and tubular atrophy have been the strongest predictive factors of renal function outcome. [15],[22] In our study, interstitial fibrosis was more frequent in the group with poor outcome.

Occurrence of remission is a good prognostic factor of renal and patient survival in LN. [9],[23] The occurrence of renal flares has been associated with deterioration of renal function. [10],[24],[25] Our results confirm these suggestions. The mean number of flares was greater in the poor prognosis group. None of the patients in the poor prognosis group had developed complete or partial remission.

In conclusion, our study confirms that among different histological factors, active lesions appear to be correlated with the clinical evolution of renal involvement. We believe that renal biopsy can provide significant prognostic information regarding the outcome in LN. However, considering the time-dependent factors such as renal flares, predicting the prognosis of LN may not always be easy at baseline biopsy.

 
   References Top

1.Houman MH, Smiti-Khanfir M, Ben Ghorbell I, Miled M. Systemic lupus erythematosus in Tunisia: Demographic and clinical analysis of 100 patients. Lupus 2004;13(3):204-11.  Back to cited text no. 1
    
2.Wadee S, Tikly M, Hopley M. Causes and predictors of death in South Africans with systemic lupus erythematosus, Rheumatology 2007;46(9):1487-91.  Back to cited text no. 2
    
3.Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003;82(5):299-308.  Back to cited text no. 3
    
4.Abu-Shakra M, Gladman DD, Urowitz MB. Mortality studies in SLE: how far can we improve survival of patients with SLE, Autoimmun Rev 2004;3(6):418-20.  Back to cited text no. 4
    
5.Lea JP. Lupus nephritis in African Americans. Am J Med Sci 2002;323(2):85-9.  Back to cited text no. 5
    
6.Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum 1982;25(11):1271-7.  Back to cited text no. 6
    
7.Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004;65(2):521-30.  Back to cited text no. 7
    
8.Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH. Prognostic factors in lupus nephritis. Contribution of renal histologic data, Am J Med 1983;75 (3):382-91.  Back to cited text no. 8
    
9.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. 9
    
10.Moroni G, Quaglini S, Maccario M, Banfi G, Ponticelli C. "Nephritic flares" are predictors of bad long-term renal outcome in lupus nephritis, Kidney Int 1996;50(6):2047-53.  Back to cited text no. 10
    
11.Donadio JV Jr, Hart GM, Bergstralh EJ, Holley KE. Prognostic determinants in lupus nephritis: A long-term clinicopathologic study, Lupus 1995;4(2):109-15.  Back to cited text no. 11
    
12.Mok CC, Wong RW, Lau CS. Lupus nephritis in Southern Chinese patients: Clinicopathologic findings and long-term outcome. Am J Kidney Dis 1999;34(2):315-23.  Back to cited text no. 12
    
13.Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD. Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 2000;35(5):904-14.  Back to cited text no. 13
    
14.Contreras G, Pardo V, Cely C, Borja E, Hurtado A De La Cuesta C. Factors associated with poor outcomes in patients with lupus nephritis, Lupus 2005;14(11):890-5.  Back to cited text no. 14
    
15.Austin HA 3rd, Boumpas DT, Vaughan EM, Balow JE. High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients. Nephrol Dial Transplant 1995;10(9):1620-8.  Back to cited text no. 15
    
16.Howie AJ, Turhan N, Adu D. Powerful morphometric indicator of prognosis in lupus nephritis. QJM 2003;96(6):411-20.  Back to cited text no. 16
    
17.Lim CS, Chin HJ, Jung YC, et al. Prognostic factors of diffuse proliferative lupus nephritis, Clin Nephrol 1999;52(3):139-47.  Back to cited text no. 17
    
18.Faurschou M, Starklint H, Halberg P, Jacobsen S. Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure. J Rheumatol 2006;33(8):1563-9.  Back to cited text no. 18
    
19.Martins L, Rocha G, Rodrigues A, Santos J, Vasconcelos C, Correia J. Lupus nephritis: a retrospective review of 78 cases from a single center, Clin Nephrol 2002;57(2):114-9.  Back to cited text no. 19
    
20.Nossent HC, Henzen-Logmans SC, Vroom TM, Berden JH, Swaak TJ. Contribution of renal biopsy data in predicting outcome in lupus nephritis. Analysis of 116 patients. Arthritis Rheum 1990;33(7):970-7.  Back to cited text no. 20
    
21.Berden JH. Lupus nephritis. Kidney Int 1997; 52(2):538-58.  Back to cited text no. 21
    
22.Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TT, Balow JE. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome, Kidney Int 1984;25(4):689-95.  Back to cited text no. 22
    
23.Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ; Collaborative Study Group. Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 2008;3(1):46-53.  Back to cited text no. 23
    
24.Mok CC, Ying KY, Tang S, et al. Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis. Arthritis Rheum 2004;50(8):2559-68.  Back to cited text no. 24
    
25.Ponticelli C, Moroni G. Flares in lupus nephritis: Incidence, impact on renal survival and management. Lupus 1998;7(9):635-8.  Back to cited text no. 25
    

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Correspondence Address:
Khawla Kammoun
Nephrology Department, Hedi Chaker Hospital, Rout El Ain Km 1, Sfax
Tunisia
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PMID: 21743218

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    Abstract
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