Predictive Factors and Long Term Outcome in Lupus Nephritis in Libya
Received Date: Feb 26, 2018 / Accepted Date: Mar 27, 2018 / Published Date: Mar 31, 2018
Lupus Nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The main purpose of this study is evaluation lupus nephritis, outcome of lupus nephritis, and studies predictive factors in lupus nephritis are improved outcome.
Patient and methods: Follow up study patients diagnosed as Systemic Lupus Erythematosus (SLE) according to the American College of Rheumatology (ACR), from the registration file of Rheumatology clinic, These patients were studied clinically for the presence of lupus nephritis, laboratory test CBP, ESR, RFT, Urine sedimentation, USS Abdomen, Doppler renal and use immunology test ANA positively was more than 1:160, anti-DNA Serum compliment levels (C3, C4), anti-ENA.
Result: Clinical presentation of lupus nephritis was asymptomatic lupus nephritis is (6.6%), Nephritis lupus nephritis (24 h urine collection<3 g/d) is (36.8%), Nephrotic disease (24 h urine collection ≥ 3 g/d) is (28.9%) and acute renal failure is (27.6%), Albumin urine collection g/d range from 0.6-6 g/24 h, M=2.1 ± 1.1, blood urea ranged from 18-200 mg/dl, M=90.9 ± 47.6, serum creatinine was 0.5-6.7 mg/dl, M=2.6 ± 1.8, Hypertension patients of lupus nephritis was (89.5%). Positive ANA was (93.4%), positive Ds DNA was (94.7%), and low complement C3, C4 was (94.7%) and positive anti cardiolipin antibody AGL was (23.7%) recurrent attack lupus nephritis was (14.5%). The renal biopsy was done found diffuse proliferative lupus nephritis was (45.5%), Focal proliferative lupus nephritis was (20.8%) and mesangial proliferative lupus nephritis was (16.9%). management of lupus nephritis and choice of therapy according guideline European League against Rheumatism (EULAR), patients were received azathioprine (13.2%), IV injection Cyclophosphamide therapy was (21.1%), mycophenolate mofetil was (55.3%) and injection rituximab was (10.5%). Outcome lupus nephritis was complete response (64.5%), Partial response was (13.2%), resistance lupus nephritis was (22.1%), end stage renal failure on hemodialysis was (7.9%), conservative chronic renal failure was (14.5%) and mortality of lupus nephritis was (13.2%)
Conclusion: Most common type diffuse proliferative lupus nephritis followed Focal proliferative lupus nephritis then mesangial proliferative lupus nephritis, induction therapy with mycophenolate mofetil or cyclophosphamide or rituximab in inducing complete remission of lupus nephritis is 64%. Even with standard therapy the end stage renal failure was (14.5%) and mortality of lupus nephritis was (13.2%) in this study. The impact of several factors like sex, age, race, duration of lupus nephritis, serum urea, serum creatinine and renal biopsy have statistical significance correlation and predictive effect on outcome lupus nephritis.
Keywords: Lupus nephritis; Mortality; Long term outcome; End stage renal disease; Prognosis
Creating a bridge between basic research and clinical medicine is a critical challenge. Research on AIM and NASH-associated HCC is now succeeding in bridging between basic research and clinical medicine.
AIM is a circulating protein produced by tissue macrophages such as Kupffer cells and peritoneal macrophages . Production of AIM is regulated by a nuclear receptor called liver X-receptor/retinoid Xreceptor . In the blood, AIM is inactivated when it associates with the IgM pentamer . AIM is almost 40 kDa and can pass through the glomerulus. Association with IgM prevents excretion of AIM in urine and enables AIM to circulate stably in the blood. The level of AIM in the blood is 4.99 ± 1.8 μg/ml and 6.06 ± 2.1 μg/ml in healthy men and women, respectively . However, in patients with specific diseases, such as obesity , acute kidney disease , and NASH-associated HCC , AIM dissociates from IgM and is activated, contributing to the recovery of each disease [8-10].
Patients and Method
The study was conducted at The 7th October University Hospital and Nephrology clinic at nephrology center between June 2013 and December 2016. Follow up study patients were diagnosed as Systemic Lupus Erythematosus (SLE) according to American College of Rheumatology (ACR), from recorded rheumatology clinic at 7th October-Hospital and nephrology clinic at nephrology center with patients with lupus nephritis, assessment clinically and laboratory test every 3 months for two years [11-14].
The correlation coefficients between mortality and different prognostic markers were calculated using Pearson’s correlation coefficient. Results were presented as percentage (%), range (median), range (mean ± 2 SD) or correlation coefficient (r). Statistical significance was defined as P<0.05.
Assessment disease activity and diagnosis lupus nephritis
Those patients were studied clinically each patient and basic simple laboratory test like complete blood picture, blood sugar, renal function test, urinalysis, 24 h. urine collection for protein and serum albumin, imaging study including USS Abdomen and Doppler renal and use immunology test ANA positively was more than 1:160, anti-DNA Serum complements levels (C3, C4), anti-ENA. Renal biopsy was advised to be done were done in-out country in Egypt or Tunis
The treatment protocol issued by European league against rheumatism and European renal association-European dialysis and transplant association (eular/era-EDTA)
Recommendations for management of Lupus Nephritis (LN) consisted of pulse glucocorticoids followed by oral Prednisolone was at a dosage of 1 mg/kg/d in addition to an immunosuppressive medication, pulses of monthly cyclophosphamide (0.75/m2-1 gm/m2 of body surface) or mycophenolate mofetil (1.5-3 gm/day) or azathioprine (2-3 mg/kg/d) as induction therapy.
Assessment outcome of lupus nephritis
Complete response: Serum creatinine 3 g/dl
Partial response; Improve serum creatinine <25% from initial value and proteinuria >50% from initial value
Resistance response: Deterioration serum creatinine increased sustained >25% from initial value and outcome as end stage renal failure.
Seventy six patients with diagnosed lupus nephritis were included in the study. Patient’s clinical characteristics are shown below (Table 1). The age of the study patients ranged from(18-50 years), M=(31.7 ± 8.1 year), 66 (86.8%) were female, the most of the patients were white 70 (92.1%) the duration of systemic lupus erythematosus disease range from (1-17 y) M=4.5 ± 3.7 y and duration of lupus nephritis range from (14-180 d) M=69.5 ± 9.5 d. Clinical Presentation of lupus nephritis was Asymptomatic lupus nephritis is 5 (6.6%) Nephritis lupus nephritis was urine collection <3 g/24 h is 28 (36.8%), nephrotic disease was urine collection ≥ 3 g/24 h is 22 (28.9%) and acute renal failure is 21 (27.6%). Respectively laboratory tests help in diagnosed lupus nephritis albumin urine collection g/d range from 0.6-6 g/24 h M=2.1 ± 1.1, blood urea ranged from 18-200 mg/dl M=90.9 ± 47.6), serum creatinine was 0.5-6.7 mg/dl, M=2.6 ± 1.8 respectively. Hypertension Patients of lupus nephritis was 68 (89.5%), the renal biopsy was done found diffuse proliferative lupus nephritis was 35 (45.5%), Focal proliferative lupus nephritis was 16 (20.8%) and mesangial proliferative lupus nephritis was 13 (16.9%), recurrent attack lupus nephritis was 11 (14.5%). Management of lupus nephritis and choice of therapy according guideline European League against Rheumatism Patients (EULAR) were received azathioprine 10 (13.2%),IV injection cyclophosphamide therapy was 16 (21.1%), mycophenolate mofetil was 42 (55.3%) and injection rituximab was 8 (10.5%). Long term outcome lupus nephritis was complete response 49 (64.5%), Partial response was 10 (13.2%), resistance lupus nephritis was 17 (22.1%), and End Stage Renal Failure on hemodialysis was 6 (7.9%). Conservative chronic renal failure was 11 (14.5%) and mortality of lupus nephritis was 10 (13.2%). We also demonstrated in Table 2 correlation between variable factors and mortality we found Statistical significance with age is -0.345**, 0.002, sex is 0.303**, 0.009, Duration of lupus nephritis is 0.259*, 0.025, recurrent attack of lupus nephritis 0.282*, 0.013, Serum urea is +0.655**, 0.000, Serum creatinine is + 0.654**, 0.000 and renal biopsy Class 4 diffuse proliferative lupus nephritis 0.235* 0.000.
|Age||18 - 50 y M=31.7 ± 8.1|
|Sex||Female 66/76 (86.8%)
Male 10/76 (13.2%)
|Race||White 70/76 (92.1%)
Black 6/76 (7.9%)
|Duration of disease||1 - 17 y M=4.5 ± 3.7|
|Duration of lupus nephritis||(14 - 180 d) M=69.5 ± 9.5|
|Acute Renal Failure (ARF)||21/76(27.6%)|
|24 h albumin urine collection g/day||0.6 - 6 g/d M=2.1 ± 1.1|
|Blood Urea mg/dl||18 - 200 mg/dl, M=90.9 ± 47.6|
|Serum Creatinine mg/dl||0.5 - 6.7 mg/dl, M= 2.6 ± 1.8|
|Recurrent attack lupus nephritis||11/76 (14.3%)|
|1.Minimal lupus nephritis||6/76 (7.9%)|
|2.Mesangial proliferative lupus nephritis||13/76 (16.9%)|
|3.Focal lupus nephritis||16/76 (20.8%)|
|4.Diffuse proliferative lupus nephritis||35/76 (45.55)|
|5.Membranous lupus nephritis||4/76 (5.2%)|
|6.Advanced sclerosing lupus nephritis||2/76 (2.6%)|
|Serology ANA||71/76 (93.4%)|
|C3, C4 Low||72/76 (94.7%)|
|Azathioprine therapy||10/76 (13.2%)|
|Cyclophosphamide therapy||16/76 (21.1%)|
|Mycophenolate mofetil||42/76 (55.3%)|
|Rituximab therapy||8/76 (10.5%)|
|Long-term renal outcome:|
|Complete response||49/76 (64.5%)|
|Partial response||10/76 (13.2%)|
|Chronic renal failure||11/76 (14.5%)|
Table 1: Patient’s clinical characteristics, lupus nephritis and general biochemical data, concomitant medications and long term outcome.
|Poor outcome lupus nephritis & mortality|
|Duration of lupus nephritis||+0.259*||0.025|
|Recurrent attack of lupus nephritis||+0.282*||0.013|
|24 h urine collection of protein||0.208||0.071|
|Serum urea mg/dl||+0.655*||0|
|Serum creatinine mg/dl||+0.654**||0|
|Anticardiolipin antibody AGL||0.211||0.061|
|Class 1-Minimal lupus nephritis||0.103||0.199|
|Class 2 Mesangial proliferative lupus nephritis
|Class 3 focal lupus nephritis||0.179||0.181|
|Class 4 diffuse proliferative lupus nephritis||0.235*||0|
|Class 5 membrane lupus nephritis||0.16||0.083|
|Class 6 Advanced sclerosing lupus nephritis||0.179||0.121|
Table 2: Correlation between poor outcome lupus nephritis & mortality and different variables.
The time course for the development of lupus nephritis varies with gender, age, and ethnicity. That enhanced risk of developing nephritis earlier in the course of the disease . The most frequently observed abnormality is proteinuria, our data shows common are Nephritis lupus nephritis then nephrotic disease and acute renal failure [16,17].
Various studies have shown that the proliferative forms of in occur more frequently than the other histological morphologies. Our data shows common are diffuse proliferative lupus nephritis followed Focal proliferative lupus nephritis then meningeal proliferative lupus nephritis.
Nephritis remains one of the most devastating complications of lupus, with the incidence of End-Stage Renal Disease due to lupus increasing between 1982 and 1995, without any decline seen by 2004. This poor outcome has occurred despite the availability of new therapeutic regimens. In our study induction therapy corticosteroid and injection cyclophosphamide 0.75/m2-1 gm/m2 or mycophenolate mofetil (1.5-2 gm/d) or azathioprine (2-3 mg/kg/d) or injection rituximab choice of therapy according guideline European League Against Rheumatism (EULAR), Long term outcome lupus nephritis was complete response (64.5%), Partial response was (13.2%), resistance lupus nephritis was (22.1%), end stage renal failure on hemodialysis was (7.9%). Conservative chronic renal failure was (14.5%) and mortality of lupus nephritis was (13.2%).
The improvement in patient with lupus nephritis is probably due to multiple factors. These include increased disease recognition with more sensitive diagnostic tests, earlier diagnosis and treatment [18,19].
Approximately 10-30% of patients with lupus nephritis progress to End-Stage Renal Disease (ESRD), depending upon the severity of the disease, socio-economic factors, noncompliance, and the response to initial treatment .
The impact of several demographic factors (sex, age, race), Duration of lupus nephritis, Serum urea Serum creatinine, recurrent attack of lupus nephritis and renal biopsy class 4 have Statistical significance correlation and predictive effect on outcome lupus nephritis. As well as reported in many studies [12-14,19,20].
Lupus nephritis is a major source of morbidity and mortality for SLE patients. Most common type diffuse proliferative lupus nephritis followed Focal proliferative lupus nephritis then mesangial proliferative lupus nephritis, induction therapy with mycophenolate mofetil or cyclophosphamide or rituximabin inducing complete remission of lupus nephritis is 64%. Even with standard therapy the end stage renal failure was (14.5%) and mortality of lupus nephritis was (13.2%) in this study. The impact of several factors like sex, age, race, duration of lupus nephritis, serum urea, serum creatinine, recurrent attack of lupus nephritis and renal biopsy have Statistical significance correlation and predictive effect on outcome lupus nephritis.
Focus researches were learned more evaluation predictive outcome lupus nephritis, needed to determine whether they can serve as both biomarkers and molecular targets for in therapy.
Limitation of Study
Small number sample because patient lost follow-up due to security conditions in the city
Conflicts of Interest
None of the authors has conflicts of interest
Grateful to all patients who participated and help in accomplishing.This work are given to my city Benghazi with hope improving health services to people.
- Kelley WN (Eds), WB Saunders, Philadelphia (2000) Clinical features of SLE. In: Textbook of Rheumatology
- Seligman VA, Lum RF, Olson JL, Li H, Criswell LA (2002) Demographic differences in the development of lupus nephritis: a retrospective analysis. Am J Med 112: 726-729.
- Bastian HM, Roseman JM, McGwin G Jr, Alarcón GS, Friedman AW, et al. (2002) Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus 11: 152-160
- Alarcon GS, McGwin G Jr, Petri M, Reveille JD, Goldman RR, et al. (2002) Baseline characteristics of a multiethnic lupus cohort: profile. Lupus 11: 95-101
- Furness PN, Taub N (2006) Interobserver reproducibility and application of the ISN/RPS classification of lupus nephritis-a UK-wide study. Am J Surg Pathol 30: 1030-1035
- Weening JJ, Agati VD, Schwartz MM, Seshan SV, Alpers CE, et al. (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15: 241-250
- Houssiau FA, Vasconcelos C, Cruz D, Sebastiani GD, Garrido Ed Ede R, et al. (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46: 2121-2131
- Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, et al. (2012) Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum 64: 1215-1226
- Schwartz MM, Kawala KS, Corwin HL, Lewis EJ (1987) The prognosis of segmental glomerulonephritis in systemic lupus erythematosus. Kidney Int 32: 274-279
- Wakasugi D, Gono T, Kawaguchi Y, Hara M, Koseki Y, et al. (2012) Frequency of class III and IV nephritis in systemic lupus erythematosus without clinical renal involvement: an analysis of predictive measures. J Rheumatol 39:79-85
- Costenbader KH, Desai A, Alarcon GS, Hiraki LT, Shaykevich T, et al. (2011) Trends in the incidence, demographics, and outcomes of end-stage renal disease due to lupus nephritis in the US from 1995 to 2006. Arthritis Rheum 63: 1681-1688
- Lim CS, Chin HJ, Jung YC, Kim YS, Ahn C, et al. (1999) Prognostic factors of diffuse proliferative lupus nephritis. Clin Nephrol 52: 139-147
- Austin HA, Boumpas DT, Vaughan EM, Balow JE (1994) Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histological data. Kidney Int 45: 544-550
- Fraenkel L, Mackenzie T, Joseph L, Kashgarian M, Hayslett JP, et al (1994) Response to treatment as a predictor of long term outcome in patients with lupus nephritis. J Rheumatol 21: 2052-2057.
- Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, et al. (2010) Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford) 49: 128-140
- Schwartz MM, Lan SP, Bonsib SM, Gephardt GN, Sharma HM (1989) Clinical outcome of three discrete histologic patterns of injury in severe lupus glomerulonephritis. Am J Kidney Dis 13: 273-283.
- Lu J, Tam LS, Lai FM, Kwan BC, Choi PC, et al. (2011) Repeat renal biopsy in lupus nephritis: a change in histological pattern is common. Am J Nephrol 34: 220-225
- Houssiau FA, Vasconcelos C, Cruz D, Sebastiani GD, Garrido RE, et al. (2010) The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 69: 61-64
- Houssiau FA, Vasconcelos C, Cruz D, Sebastiani GD, Garrido RE, et al. (2004) Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term follow up of patients in the Euro-Lupus Nephritis Trial. Arthritis Rheum 50: 3934-3940
- Ortega LM, Schultz DR, Lenz O, Pardo V, Contreras GN (2010) Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions. Lupus 19: 557-574.
Citation: Zaid FE, Salem MB (2018) Predictive Factors and Long Term Outcome in Lupus Nephritis in Libya. Rheumatology (Sunnyvale) 8: 234. Doi: 10.4172/2161-1149.1000234
Copyright: ©2018 Zaid FE, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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