Background: Lupus nephritis (LN) is a known complication of systemic lupus erythromatosis (SLE).

Aim: To study the relationship between clinical features of SLE and LN classes at presentations.

Method: Patients’ files were reviewed retrospectively for the clinical symptoms, signs, laboratory results and histopathology reports of kidney biopsy of SLE patients for 8 years. All patients had CBC, bleeding and clotting time. Blood pressure measured before conducting percutaneous renal biopsy (PRB). 

Statistical analysis: Data was collected and analyzed by IBM-SPSS version19.0 (SPSS, Chicago, IL, USA).Student’s t-test, one-way ANOVA and analysis of variance were used for statistical analysis. P < 0.05 was considered statistically significant.

Results: One-hundred twenty seven SLE patients files’ were reviewed, 51 patients had been diagnosed as LN after their PRB specimens examined by pathologist. Patients were 44 females (86.3%), 7 males (13.7%), with a mean age of 31 year ± 2.3 (standard error of mean). Bilateral lower limbs (BLL) edema and hypertension (HTN) reported in 16 patients (31%), BLL edema and hematuria detected in 12 patients (24%), BLL edema only reported in 7 patients (14%). Generalized edema plus hematuria described in 6 patients (12%). Oliguria with muscle weakness and generalized edema described in 4 patients (8%).Muscle weakness and generalized edema reported in 3 patients (6%), and BLL edema plus face puffiness only reported in 3 patients (6%). White blood cell count (WBC) mean was 8.46 x 103 ± 0.57, ranged between 4.8 -13.0 x 103 / µl. Hemoglobin mean was (11.4g ± 0.22), ranged (9.5 – 13g/dl). Platelets mean was 170 x 103 /µl ± 10.3, ranged between 124 – 301x 103 /µl. Erythrocyte sedimentation rate (ESR) ranged between 2.00 – 84.00 mm after 1st hour, with a mean of 40 ± 5.86.Mean protein excretion in urine/24 hours was 2.22g/L ± 0.19, 0.30 – 2.22 g/L. LN activity index mean was (5 ± 1.0) ranged0.00 – 14. Chronicity index mean (1.95 ± 0.52), and ranged between 0.00 – 10.00. Histopathological findings were; Class I reported in 7 patients (14%), class II in 11 patients (22%).Class III reported in 5 patients (10%), class IV in 18 patients (35%) and class V in 10 patients (20%). Advanced sclerotic LN (class VI) was not described in the studied patients. Patients’ age affected protein excretion in 24hrs urine, LN activity and chronicity index significantly (P = 0.02, P< 0.0001, P< 0.0001) respectively. Multivariate analysis revealed significant correlation between LN classes and protein excretion in urine/day, i.e. class III, IV and V had significantly increased protein excretion in urine P = 0.04, 0.025 and 0.021respectively. LN class IV associated significantly with BLL edema only, and with BLL edema plus facial puffiness at presentation (p = 0.01, P=0.02).

Conclusion: Clinical feature and 24 hours protein excretion in urine were related significantly to LN classes and patients’ age at presentation. Early detection of clinical SLE features, and LN classes will reduce subsequent complications and health services cost.

•    SLE
•    HTN
•    LN classes
•    Nephritis
•    Proteinuria

Habas E, Turjman F, Rayani A, Elamour J, Tabib M, et al. (2016) SLE Nephritis Clinical Features and Renal Lesion: Tripoli Central Hospital Experience. J Chronic Dis Manag 1(2): 1006.

SLE has a wide spectrum of clinical and immunological abnormalities.SLE etiology and pathogenesis are not clearly identified. Autoimmune reactions due to improper central or peripheral deletion of auto-reactive lymphocytes in SLE had been attributed to SLE pathogenesis and etiology, and that led to formation of characteristic auto antibodies to double strand-DNA, nuclear antigens and membrane phospholipids [1-4]. Furthermore, it had been claimed that abnormal immune regulatory mechanisms, environmental and genetic risk factors might had stimulatory autoimmune reactions in susceptible people [5,6].

LN appears to be more prevalent in certain ethnic groups. It was reported that 45% of African Americans, 42% of Chinese, and 30% of Caucasian SLE patients had evidences of renal involvement [7]. Another multi-ethnic USA cohort study of SLE patients reported that renal disease occurred in 51% of Africans and 43% of Hispanics and in 14% of Caucasians [8]. Chinese patients with new onset SLE, 31% patients had active renal disease at first presentation [9], and the overall incidence of LN was 60% after 5 years post-SLE diagnosis [10].

Kidney involvement by LN classified into six different classes [5]. Although LN has different clinical and histological features, there is usually intercrossing among the LN microscopic histopathological findings. Mixed LN lesions and transformation of one lesion to other due to disease progression were reported in about 35% of LN patients [11].

SLE is not uncommon diseases in Libya particularly in female. Up to our knowledge, there were not any published data about the commonest LN class, and any relationship between clinical features and LN classes at presentation. Therefore, this study was conducted to study the common LN classes and to assess any relationship between the clinical presentation and LN classes.

Clinical data of 127SLE patients were collected. They were 104 females and 23 males. Ultrasound guided PRBs were done for 59 patients. Only 51biopsies had sufficient PRB specimens for histopathological examination [12]. PRBs were conducted at Medical Department, and examined microscopically in Pathology Department at Tripoli Central Hospital -Libya, during May 2008 - Sept 2016.

Biopsy specimens were sent to pathology department in container containing 4.5% buffered formaldehyde. Specimens were sectioned and stain by hematoxylin and eosin (H&E), periodic acid-Schiff. Pathological parameters of disease activity and chronicity were done by pathologists according to semi-quantitative scoring system of biopsy specific features [13-15]. LN lesions were reported according to the International Society of Nephrology and Renal Pathology Society of lupus nephritis classification system (Figure 1).

Figure 1: Revised classification of LN[5]

Statistical analysis

Statistical analysis was conducted by IBM-SPSS, version19.0 statistical software (SPSS, Chicago, IL, USA). Quantitative data were expressed as (mean ± SEM), and range (minimum, maximum). Student’s t-test, one-way ANOVA analysis of variance were used to test the significant relation between clinical features and LN classes at presentation. P value of <0.05 was considered statistically significance.

LN patients were 44 females and 7 males. Male patients’ age ranged between 28 – 49 years and female patients’ age ranged between 17 – 38 years. Mean age of the studied patients was31 year ± 2.3, with standard deviation (STD) of 10.3, and variance (var) of 100 (Table 2).

Patients had BLL edema and hypertension were 16 patients (31%). BLL edema and hematuria reported in 12 patients (24%), BLL edema only was detected in 7 patients (14%). Generalized edema plus hematuria observed in 6 patients (12%), and generalized edema with HTN reported in 6 patients (12%). Generalized edema, muscle weakness and oliguria reported in 4 patients (8%), and generalized edema plus muscle weakness reported in 3 patients (6%).BLL edema with facial puffiness detected in 3 patients (6%) (Table 1).

Table 1: Symptoms and signs at presentation.

One or two days before PRB appointment; WBC count was normal in most of patients with a mean of 8.500 ± 0.57 and range of4.8 -13.0 x 103 /µl, STD of 2.5 and var of 6.24. Hemoglobin ranged between 9.5 – 13g/dl with a mean of 11.3 ± 0.22. Platelets count ranged between 124 – 301x 103 /µl with a mean of 170 x 103 /µl ± 10.3, STD 45.1 and var of 210.8. ESR ranged between 2.00 – 84.00 with a mean of 40 ± 5.86, and STD of 25.6, and var of 653.1.

Protein excretion in urine/24 hours ranged between 0.30 – 2.22gm/L with a mean of 4.00gm/L ± 0.84, and STD of 4.38, and var of 5.16. LN activity index ranged with 0.00 – 14, with a mean of 5.00 ± 1.01, STD of 4.38 and var of 5.16. Chronicity index of LN ranged between 0.00 – 10.00, with a mean of 1.95 ± 0.52, STD of 2.27 and var of 19.22. (Table 2).

PRB specimens’ histopathological examination revealed; Class I- (minimal mesangial) LN was detected in 7 patients (14%). Class II- (Mesangial proliferative) LN was detected in 11 patients (22%), class III-(focal) LN was detected in 5 patients (10%). Class IV- (diffuse) LN was reported in 18 patients (35%). Class V- (membranous) LN was seen in 10 patients (20%). Class VI - LN was not reported in the studied patients (Table 2).

Table 2: Patients’ age, blood tests, protein in urine, LN activity and chronicity at presentation.

Protein excretion in urine/day, LN activity and chronicity were significantly affected by an increase of patients’ age (P = 0.02, P < 0.0001, P <0.0001 respectively). Furthermore, statistical analysis revealed significant increase of protein excretion in urine in class III, IV and V LN (P = 0.04, P =0.025 and P =0.021 respectively). BLL edema only, and BLL edema with facial puffiness increased significantly with an increase of patients’ age (p = 0.01, P=0.02 respectively), as well LN activity and chronicity were significantly affected by patients’ age increase (P<0.0001) (Table 3).

Table 3: LN classes, and their frequency and percentage at presentation.

Kidney injuries are either due to local renal diseases as pyelonephritis or manifestations of systemic diseases such as SLE, amyloidosis and vasculitis or both. Detection of LN pathological class, activity and chronicity are essential for management and prognosis in LN [16,17]. Clinical symptoms, signs and laboratory results at first presentation and follow up in SLE patients are important, and must be considered carefully, while they are important for prediction of LN classes in about 70-80% of LN patients [18-20].

Literatures review showed that SLE was more predominated in female with a ratio of 9:1(female: male). In this study, patients diagnosed as SLE patients were 127 patients. They were 82% female and 18% males (8.2:1.8 ratio female: male). This ratio was not different significantly from the previous reported ratio.

Hanly et al., reported that about 38% of SLE patients had LN, and LN was more common in women than men in certain ethnic groups [21]. Our results revealed that LN lesions were found in about 40.1% of patients participated at presentation, and showed females had LN more than males (44 females and 7 males (8.6:1.4). LN predominance in females reported in this study supported Hanly et al., and Lim & Drenkard reported data [21,22]. The higher rate of LN observed in this series in females was possibly because, the patients were mostly females and /or PRB acceptance by females was more than males. Reasons made male patients refused PRB than females were not clear.

Clinical symptoms and signs as BLL swelling, puffiness of face, increase body weight, dyspnea, and muscle weakness were reported in patients enrolled in this study with different proportions. In this study, 24 hours protein excretion in urine ranged between 300mg-4.00gm/24h/1.75 m2 , while normally in Man, protein excretion in urine is about 150-200 mg/day/1.75 m2 . Protein excretion in urine increased significantly with an increase in patients’ age, and also with LN class III & IV at presentation in this study. The presenting symptoms and signs significant correlation with protein excretion and LN classes, this might be due to increased protein loss in urine. The increased protein excretion in urine could be due to late presentation in some patients and/or LN progression, and the associated heart comorbidity that was reported common with heavy proteinuria [23].

Our results showed that class I reported in 14%, class II in 22%, class III in 10%, and class V in 20% of the studied patients. Class IV was the commonest LN classes in this series (35%). The higher frequency of class IV LN in this study might be due to late presentation and/or delay in conducting PRB. Furthermore, increased percentage of class IV at presentation may explain the significant association between symptoms, signs and proteinuria with class IV-LN at presentation.

Clinical features and patients’ age are significantly related to LN classes at presentation. Early diagnosis of SLE and LN by clinical features and histopathology are essential for early treatment to reduce late complications and services cost.

Authors would like to acknowledge the help and assistance of all the doctors and nurses, pathology technicians and other collogues for their support and help to finish this work. We would like to acknowledge that this work is not financially supported by any one.

1. Yung S, Chan TM. Anti-DNA antibodies in the pathogenesis of lupus nephritis--the emerging mechanisms. Autoimmun Rev. 2008; 7: 317- 321.

2. Mecklenbräuker I, Saijo K, Zheng NY, Leitges M, Tarakhovsky A. Protein kinase Cdelta controls self-antigen-induced B-cell tolerance. Nature. 2002; 416: 860-865.

3. Stuart L, Hughes J. Apoptosis and autoimmunity. Nephrol DialTranspl. 2002; 17: 2697-2700.

4. Walport MJ, Davies KA, Botto M. C1q and systemic lupus erythematosus. Immunobiology. 1998; 199: 265-285.

5. Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Am SocNephrol. 2004; 15: 241-250

6. Appel GB, Silva FG, Pirani CL. Renal Involvement in Systemic Lupus Erythematosus (SLE): A Study of 56 Patients Emphasizing Histologic Classification. Medicine. 1978; 75: 371-410.

7. Mok CC, Tang SS, To CH, Petri M. Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum. 2005; 52: 2774-2782.

8. Bastian HM, Roseman JM, McGwin G Jr, Alarcón GS, Friedman AW, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus. 2002; 11: 152-160.

9. Mok CC, Tang SS. Incidence and predictors of renal disease in Chinese patients with systemic lupus erythematosus. Am J Med. 2004; 117: 791-795.

10. Bhinder S, Singh A, Majithia V. Membranous (class V) renal disease in systemic lupus erythematosus may be more common than previously reported: results of a 6-year retrospective analysis. Am J Med Sci. 2010; 339: 230-232.

11. Mercadal L, Montcel ST, Nochy D, Queffeulou G, Piette JC, Isnard-Bagnis C, et al. Factors affecting outcome and prognosis in membranous lupus nephropathy. Nephrol Dial Transplant. 2002; 17: 1771-1778.

12. Habas E, Elhabash B, Rayani A, Turgman F and Tarsien R. Post-Percutaneous Renal Biopsy Observation Time; Single Center Experience. Austin J Nephrol Hypertension. 2016; 3: 1-4.

13. Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1989; 32: 1107-1118.

14. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992; 35: 630-640.

15. Mok CC, Birmingham DJ, Leung HW, Hebert LA, Song H, Rovin BH. Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis. Rheumatology (Oxford). 2012; 51: 644-652.

16. Mok CC, Wong RW, Lai KN. Treatment of severe proliferative lupus nephritis: the current state. Ann Rheum Dis. 2003; 62: 799-804.

17. Grande JP, Balow JE. Renal biopsy in lupus nephritis. Lupus. 1998; 7: 611-617.

18. Dooley MA. Clinical and epidemiologic features of lupus nephritis. Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus and Related Syndromes. 8th ed. Philadelphia, PA: Elsevier Saunders; 2013. 438- 454.

19. Smith EM, Jorgensen AL, Midgley A, Oni L, Goilav B, Putterman C, et al. International validation of a urinary biomarker panel for identification of active lupus nephritis in children. Pediatr Nephrol. 2016. 1-10.

20. Sinico RA, Rimoldi L, Radice A, Bianchi L, Gallelli B, Moroni G. Anti-C1q autoantibodies in lupus nephritis. Ann N Y Acad Sci. 2009; 1173: 47-51.

21. Hanly JG, O’Keeffe AG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology. 2016: 55; 252- 262.

22. Lim SS, Drenkard C. The Epidemiology of Lupus. Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus and Related Syndromes. 8th ed. Philadelphia, PA: Elsevier Saunders; 2013. 8-24.

23. Faurschou M, Mellemkjaer L, Starklint H, Kamper AL, Tarp U, Voss A, et al. High risk of ischemic heart disease in patients with lupus nephritis. J Rheumatol. 2011; 38: 2400-2405.