Retrospective analysis of nephritis response and renal outcome in a cohort of 928 Egyptian lupus nephritis patients: a university hospital experience

Abstract

Aim

We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors.

Methods

We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals.

Results

Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients (p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) (p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) (p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually (p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome (p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years’ mortality was 69 (7.4%) patients with sepsis being the main cause of death.

Conclusion

IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.

Keywords

Systemic lupus erythematosus lupus nephritis cyclophosphamide mycophenolate mofetil azathioprine renal outcomes Egyptian patients

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References

Mok

. Cyclophosphamide for the treatment of lupus nephritis. Nephrol Dial Transplant 2016; 31: 1053–1057.

Mok

. Prognostic factors in lupus nephritis. Lupus 2005; 14: 39–44.

Contreras

Pardo

Leclercq

et al.

Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004; 350: 971–980.

Zhu

Chen

Lin

et al.

Mycophenolate mofetil in induction and maintenance therapy of severe lupus nephritis: a meta-analysis of randomized controlled trials. Nephrol Dial Transplant 2007; 22: 1933–1942.

Lee

Song

. Comparative efficacy and safety of tacrolimus, mycophenolate mofetil, azathioprine, and cyclophosphamide as maintenance therapy for lupus nephritis: a Bayesian network meta-analysis of randomized controlled trials. Z Rheumatol 2016, pp. 1–9.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

Saseen

MacLaughlin

. Hypertension. DiPiro

Talbert

Yee

Matzke

Wells

Posey

. Pharmacotherapy: a pathophysiologic approach, 9th ed. New York: McGraw-Hill Medical, 2014, pp. 49–84.

Cockcroft

Gault

. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41.

Weening

D'Agati

Schwartz

et al.

The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65: 521–530.

10.

Liang

Schur

Fortin

et al.

The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Arthritis Rheum 2006; 54: 421–432.

11.

Mills

. Systemic lupus erythematosus. N Engl J Med 1994; 330: 1871–1879.

12.

Resende

Titan

Barros

Woronik

. Worse renal outcome of lupus nephritis in male patients: a case-control study. Lupus 2011; 20: 561–567.

13.

Hsu

Chiu

Yang

et al.

Age- and gender-related long-term renal outcome in patients with lupus nephritis. Lupus 2011; 20: 1135–1141.

14.

Schwartzman-Morris

Putterman

. Gender differences in the pathogenesis and outcome of lupus and of lupus nephritis. Clin Dev Immunol 2012; 2012: 604892–604892.

15.

Donadio

Jr Hart

Bergstralh

Holley

. Prognostic determinants in lupus nephritis: a long-term clinicopathologic study. Lupus 1995; 4: 109–115.

16.

Cortés-Hernandez

Ordi-Ros

Labrador

et al.

Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone. Lupus 2003; 12: 287–296.

17.

Beji

Kaaroud

Ben Moussa

et al.

Lupus nephritis: 211 cases. Rev Med Interne 2005; 26: 8–12.

18.

Franco

Yoo

Franco

. Predictors of end stage renal disease in African Americans with lupus nephritis. Bull NYU Hosp Joint Dis 2010; 68: 251–256.

19.

Ayodele

Okpechi

Swanepoel

. Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis. Nephrology 2010; 15: 482–490.

20.

Korbet

Lewis

Schwartz

Reichlin

Evans

Rohde

. Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis 2000; 35: 904–914.

21.

Moroni

Ventura

Riva

et al.

Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis. Am J Kidney Dis 2004; 43: 28–36.

22.

Kammoun

Jarraya

Bouhamed

et al.

Poor prognostic factors of lupus nephritis. Saudi J Kidney Dis Transpl 2011; 22: 727–732.

23.

Mok

Lau

Chan

Wong

. Clinical characteristics and outcome of southern Chinese males with systemic lupus erythematosus. Lupus 1999; 8: 188–196.

24.

Hsieh

Chang

Brandt

Guttikonda

Utset

Clark

. Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res 2011; 63: 865–874.

25.

Hiramatsu

Kuroiwa

Ikeuchi

et al.

Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions. Rheumatology 2008; 47: 702–707.

26.

Chen

Tang

Zhang

Liu

. Prediction of renal outcomes in patients with crescentic lupus nephritis. Am J Med Sci 2015; 349: 298–305.

27.

Chen

Tang

Zhang

et al.

Significance of histological crescent formation in patients with diffuse proliferative lupus nephritis. Am J Nephrol 2013; 38: 445–452.

28.

Moon

Park

Kwok

et al.

Predictors of end-stage renal disease and recurrence of lupus activity after initiation of dialysis in patients with lupus nephritis. Clin Exp Rheumatol 2013; 31: 31–39.

29.

Austin

3rd Boumpas

Vaughan

Balow

. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int 1994; 45: 544–550.

30.

Appel

Contreras

Dooley

et al.

Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009; 20: 1103–1112.

31.

Ginzler

Dooley

Aranow

et al.

Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353: 2219–2228.

32.

Houssiau

D'cruz

Sangle

et al.

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010; 69: 2083–2089.

33.

Dooley

Jayne

Ginzler

et al.

Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 2011; 365: 1886–1895.

34.

Haddiya

Hamzaoui

Tachfouti

et al.

Features and outcomes of lupus nephritis in Morocco: analysis of 114 patients. Int J Nephrol Renovasc Dis 2013; 6: 249–258.

35.

Cervera

Khamashta

Font

et al.

European Working Party on Systemic Lupus Erythematosus. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1000 patients. Medicine 2003; 82: 299–308.

36.

Al Durahim

Al Ghamdi

Al Seraya

et al.

Predictors of mortality and end stage renal disease in Saudi patients with lupus nephritis. Lupus 2011; 20: 1329–1335.

37.

Chen

Tang

Liu

et al.

Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: a multicenter randomized clinical trial. Am J Kidney Dis 2011; 57: 235–244.

38.

Mok

Ying

et al.

Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am J Med 2006; 119. 355.e25–355.e33.

39.

Velásquez

Verdejo

Massardo

et al.

Outcome of Chilean patients with lupus nephritis and response to intravenous cyclophosphamide. J Clin Rheumatol 2003; 9: 7–14.

40.

Contreras

Tozman

Nahar

et al.

Maintenance therapies for proliferative lupus nephritis: mycophenolate mofetil, azathioprine and intravenous cyclophosphamide. Lupus 2005; 14(suppl 1): s 33–s38.

41.

Pryor

Bologna

Kahl

. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 1475–1482.