Factores predictores del desarrollo de nefritis lúpica después del diagnóstico de lupus eritematoso sistémico

ObjectiveTo determine predictive factors for the development of lupus nephritis (LN) at the time of diagnosis of systemic lupus erythematosus (SLE).MethodsA case-control study was carried out in a single centre, 595 patients participated diagnosed with SLE without LN by clinical or laboratory parameters at diagnosis. They were followed for a mean of 6.8 (± 4.5) years, two groups were formed from the data from their records: with NL (cases) and without NL (controls) at the end of the follow-up. Sociodemographic, clinical, serological, immunological variables and albumin/globulin ratio (AGR), calculated as albumin / total protein ? albumin at diagnosis, were compared between both groups. A univariate and multivariate analysis was carried out.Results124 (20.8%) patients had LN during follow-up and 471 (79.2%) did not develop LN. Univariate analysis: variables significantly associated with the development of LN: smoking, oral ulcers, serositis, more than four classification criteria, abrupt onset of SLE, higher SLEDAI score, low AGR, low C3 levels, high anti-titres double stranded DNA (anti-dc DNA), anti-nucleosomes and positivity of immunofluorescence in skin. Multivariate analysis: predictors of developing LN: elevated serum levels of anti-dc DNA (odds ratio [OR]: 15.82; confidence interval [CI]: 1.08-1.22, P < .0001), decrease in C3 fraction (OR: 36.50; CI: 13.52-81.91, P < .0001) and RAG < 1 (OR: 47.58; CI: 11.85-79.17, P < .0001).ConclusionAn AGR below one was the greatest predictor of the appearance of LN, together with low levels of C3 and high levels of anti-dc DNA antibodies; these may contribute to identifying patients at higher risk of presenting LN.     

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p < 0.001). There were significant correlations between IL-18 and SLEDAI (p = 0.002), proteinuria (p = 0.027), renal activity score (p = 0.003) and activity index (p = 0.039) in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN.ConclusionIL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE.     

Anti-nucleosome antibodies: A potential surrogate marker for renal affection in lupus patients with insignificant proteinuria

BackgroundLupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). Clinical renal involvement is present in about two-thirds of lupus patients and more patients would have morphologic evidence of renal disease without clinical manifestations.Aim of the workTo investigate serum anti-nucleosome antibodies role as a biomarker for renal affection in lupus patients with insignificant proteinuria.Patients and methodsTwenty-four lupus patients with proteinuria <500 mg/d (group-A), 30 patients with established lupus nephritis (group-B) and 15 controls were included. Systemic lupus erythematosis disease activity index (SLEDAI), anti-nucleosome, anti-dsDNA antibodies and renal biopsy were assessed in all patients.ResultsSerum anti-nucleosome antibodies were significantly higher in all lupus patients than control (P < 0.001) and showed significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibody had more active disease by SLEDAI and higher levels of anti-nucleosome antibodies than those with negative anti-dsDNA antibodies. In both studied groups, serum anti-nucleosome antibodies were significantly higher in patients with class II LN than the control and in class III LN than in class II LN (P < 0.001). Yet, in both groups, anti-nucleosome was not useful in differentiating active from chronic renal affection.ConclusionSerum levels of anti-nucleosome antibodies are associated with active lupus disease and correlate with the degree of renal affection. In patients with insignificant proteinuria, serum levels of anti-nucleosome antibodies were elevated and were related to the degree of renal affection. Anti-nucleosome antibodies may be used as a surrogate marker for early renal affection in lupus patients with insignificant proteinuria.     

Resistin in systemic lupus erythematosus: Relation to lupus nephritis and premature atherosclerosis

BackgroundLupus nephritis (LN) is one of the most severe complications of SLE. SLE patients have a greater risk of developing premature atherosclerosis. Resistin is an adipocyte-secreted peptide. It has pro-inflammatory and atherogenic effects.Aim of the workTo assess the serum levels of resistin in SLE patients and to evaluate it as a marker of nephritis and premature atherosclerosis.Patients and methodsThis study included 50 SLE nonpregnant female adult (mean age 23.1 ± 6.9 years) patients as well as 40 healthy volunteers matched in age and sex as a control group. Serum levels of resistin were assayed using enzyme-linked immunosorbent assay (ELISA). All patients and controls underwent laboratory investigations and carotid duplex. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). Renal biopsy was performed for SLE patients with LN.ResultsThere was a highly statistically significant increase in mean serum resistin levels (14.1 ± 3.88 ng/ml) in patients versus the control group (6.44 ± 1.34 ng/ml) being more obvious in those with LN. Resistin had a significant positive correlation with markers of inflammation, SLEDAI and carotid intima media thickness (CIMT).ConclusionSerum level of resistin may serve as a marker of LN and atherosclerosis in SLE patients. A more aggressive control of the underlying inflammatory process along with the control of traditional risk factors (hypertension and cholesterol) may be beneficial in reducing the risk factors of renal and atherosclerotic involvement in SLE. Therapeutic approaches with drugs that target resistin might be useful in the treatment of SLE.     

Evaluation of visfatin in patients with systemic lupus erythematosus: Correlation with disease activity and lupus nephritis

IntroductionRenal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients. The adipokine “visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease.Aim of the workTo assess serum visfatin level in SLE patients and its correlation to disease activity and lupus nephritis (LN) in these patients.Patients and methodsSerum level of visfatin using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of SLE and LN were measured in 40 SLE patients and 40 age and sex matched healthy controls. Disease activity and renal involvement were assessed using SLE Disease Activity Index (SLEDAI) and Renal SLEDAI respectively further dividing patients into active versus inactive and LN versus non-LN respectively. Renal biopsies were taken from LN subgroup and were classified according to the modified WHO classification.ResultsA significantly higher serum visfatin level was found on comparing SLE patients (mean 109 ± 180 ng/ml, median18) with controls (mean 9.4 ± 11 ng/ml, median2.5) with statistically highly significant difference (z = 5.2, P < 0.001). Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173 ± 111 ng/ml, median 14) and inactive patients (mean 139 ± 88 ng/ml, median 5) (z = 2.1, P < 0.05) as well as between patients with LN (mean 226 ± 180 ng/ml, median18) and patients with no LN (mean 101 ± 140 ng/ml, median 8(2-229)) (z = 2.1, P < 0.05). Visfatin had a highly significant positive correlation with disease duration (r = 0.48, P < 0.001), SLEDAI (r = 0.62, P < 0.001) as well as ESR, CRP and, renal score (r = 0.45, 0.35, and 0.65, respectively) while inverse correlation with estimated GFR (r = ?0.614) and C3 and C4 titre (r = ?0.26, r = ?0.35, respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE and LN 83% and 85%, respectively.ConclusionSerum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score and GFR decline. Further prospective studies are required to confirm visfatin as a destructive mediator of predictive and prognostic value in active lupus nephritis.     

¿Es la nefritis lúpica un factor pronóstico en el embarazo? Resultados maternos y fetales

BackgroundPregnancy in women with systemic lupus erythematosus (SLE) and nephritis (LN) is at risk of foetal and maternal complications.ObjectiveTo evaluate the effect of LN on pregnancy with respect to foetal and maternal outcome.MethodsWe retrospectively studied all pregnant SLE patients with and without diagnosis of LN, who attended the Materno Neonatal Hospital in Cordoba city, Argentina, from January 2015 to April 2017. Demographic, clinical, and laboratory data were collected. The presence of antiphospholipid syndrome (APS) and antiphospholipid antibodies (AAF), and maternal and foetal outcome were evaluated.Results121 pregnancies in 79 patients were included. Pregnancies were divided into those with LN (69) and those without LN (52). The presence of APS and AAF was more frequent in the LN group as well as higher basal SLEDAI. The LN group received more immunosuppressive therapy and increased steroid dose treatment. Of the patients, 47.5% had Class IV LN. Lupus flares occurred more frequently in the LN group 25.8% vs 10.9% in the group without LN (P = .041), mainly renal flares in the LN group. No patients developed end-stage renal failure. Preeclampsia was more frequent in the LN group, 18.8% vs 6.3% in the group without LN (P = .047). There was only one maternal death. A caesarean section was required in 68.5% of the LN group vs 31.5 in the group without LN, and urgent caesarean section was also performed in the LN group. There were no differences in foetal outcomes in either group: live birth, gestational age, weight birth, perinatal death, foetal distress.ConclusionsPatients with LN experienced more maternal complications such as lupus flares and preeclampsia. However, LN does not lead to a worse pregnancy and foetal outcome. Patients should be strictly monitored before and after conception.     

Interleukin-27 and its relation to disease parameters in SLE patients

IntroductionIL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models, suggesting that it may be therapeutically relevant in SLE.Aim of the workTo evaluate IL-27 level in SLE patients and its association to clinical manifestations, disease activity parameters and management strategy.Patients and methodsWe studied 80 SLE patients and 50 controls in a cross sectional study. Demographic, clinical and serological data were evaluated. Systemic lupus erythematosus disease activity index (SLEDAI) and Systemic Lupus International Collaboration Clinics/ACR damage index (SLICC) were assessed. Serum IL-27 was measured by ELISA.ResultsThere was statistically significant difference in IL-27 level in SLE patients and healthy controls (9.7 ± 21.9 pg/ml vs 20.2 ± 47.3 pg/ml in SLE vs controls, respectively) (p = 0.04), also it was found that IL-27 level was statistically significantly lower in SLE patients with lupus nephritis (p = 0.02) and cerebritis (p = 0.03). Interleukin 27 level had a statistically significant negative correlation with the cumulative dose of hydroxychloroquine and azathioprine (r = ?0.3, p = 0.03 and r = ?0.3 and p = 0.04, respectively).ConclusionIL-27 has anti-inflammatory effect in SLE patients especially those without nephritis or cerebritis and can be therapeutically relevant in SLE. To confirm our results we propose larger scale, multicentre studies with longer evaluation periods.     

Predictores de respuesta al tratamiento en pacientes con nefritis lúpica

ObjectiveTo identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment.Material and methodsWe analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated.ResultsWe reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30 ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment.ConclusionsThere are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years.     

Neutrophil to lymphocyte and platelet to lymphocyte ratios in systemic lupus erythematosus: Relation with disease activity and lupus nephritis

ObjectivesTo investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients.Patients and methodsThis study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection.ResultsThe NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24 h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9.ConclusionNLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging.     

Lymphopenia and systemic lupus erythematosus,a preliminary study: Correlation with clinical manifestations,disease activity and damage indices

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production against ‘self’ antigens and immunocomplex formation, resulting in frequent widespread inflammatory damage to target multiple organ systems.Aim of workTo determine the association of lymphopenia with the clinical manifestations, serologic abnormalities, disease activity and disease damage as well as drug intake in SLE patients.Patients and methodsThe present study was carried out on forty-five SLE female patients fulfilling the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE. They were divided into two groups according to the lymphocytes’ count: Group-I: thirty patients with lymphopenia (<1500/mm³) and group-II: fifteen patients without lymphopenia (⩾1500/mm³). Ten healthy age matched females (group-III) taken as a control group. Patients and control groups were recruited from the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University Hospitals. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Disease damage was assessed with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index.ResultsLymphopenia in patients with SLE was found to be associated with lupus nephritis (p = 0.023), leucopenia (p = 0.004), increased disease activity index (p = 0.03) and increased organ damage index (p = 0.02), and was not associated with other clinical lupus manifestations, serological abnormalities or with the drug intake (p > 0.05).ConclusionLymphopenia in SLE was associated with lupus nephritis, leucopenia and increased both disease activity and organ damage indices.     

Membranous (Class V) Renal Disease in Systemic Lupus Erythematosus May Be More Common Than Previously Reported: Results of a 6-Year Retrospective Analysis

BackgroundThe actual incidence and prevalence of the various histological classes (based on World Health Organization classification) of lupus nephritis (LN) are not known but seem to vary with sex, age, and ethnicity. We have analyzed renal biopsies in patients with systemic lupus erythematosus (SLE) at our center, and hereby report our experience.MethodsAll renal biopsies performed at the University of Mississippi between January 1999 and December 2004 in patients with SLE were retrospectively analyzed. Results were validated by a detailed review of renal biopsy reports and additional records were reviewed for data specific to LN disease activity.ResultsThere were 92 renal biopsies performed in patients with SLE during a 6-year period. These included 84 African Americans (72 women and 12 men), 5 whites (4 women and 1 man), and 3 unknown race (1 F, 2 M) subjects. The prevalence of LN classes in our cohort was as follows: class I (0%), class II (9.8%), class III (8.7%), class IV (36.9%), class V (40.2%), and class VI (4.3%). Prevalence of class V LN among males was high at 40%.ConclusionsIn contrast to previous literature, isolated membranous lupus nephritis (MLN) was much more prevalent in this series—40% versus 14%. Also, no sex difference in the prevalence of MLN was seen. This biopsy cohort suggests that MLN/ class V disease may be more common than previously reported especially in African American population.     

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study

Objectives

Urinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis.

Trasplante renal en lupus eritematoso sistémico: comparación de la supervivencia del injerto con otras causas de enfermedad renal terminal

Introduction

End-stage renal disease (ESRD) due to lupus nephritis (LN) occurs in 10%-30% of patients. Initially systemic lupus erythematosus (SLE) was a contraindication for kidney transplantation (KT). Today, long-term graft survival remains controversial. Our objective was to compare the survival after KT in patients with SLE or other causes of ESRD.

Factores de riesgo predictores de falla a la terapia de inducción de nefritis lúpica en una cohorte de pacientes colombianos

ObjectivesTo determine the predictors of failure to obtain remission after induction therapy for proliferative lupus nephritis in a group of northwestern Colombian patients.Material and methodsA retrospective study was conducted. We included patients with systemic lupus erythematosus according to the American College of Rheumatology criteria who had nephritis confirmed by renal biopsy.ResultsWe followed 84 patients: 88.1% female, and 11.9% male. The mean age at diagnosis of systemic lupus erythematosus was 27.5 ± 11.8 years (9-70). The average time between diagnosis of systemic lupus erythematosus and proliferative nephritis onset was 13.6 months (0-168). Histopathologic type: iv (78.57%), iii (15.47%), iii-iv/v (5.96%). Activity index: 6.7 ± 4.6. Chronicity index: 2 ± 2.7. 24-hour proteinuria (mg): 6,164 (130-18,100). Baseline creatinine: 1.14 mg/dL (0.43-7.4). Induction therapy: Steroids (100%), cyclophosphamide (76.2%) and mycophenolate mofetil (23.8%). At six months, 56% of individuals failed to achieve partial or complete remission. Predictors of failure to induction therapy were, in accordance with the bivariate analysis (OR; 95% CI): creatinine level more than 1.2 mg/dL (10.8; 3.18-36.84; P < .005), nephrotic range proteinuria (11.9; 3.09-45.8; P < .001), and an activity index above 8 (5.04; 1.7-14.3; P < .001). In the multivariate analysis, only baseline creatinine higher than 1.2 mg/dL (10.92; 2.65-45.02; P = .001), and nephrotic range proteinuria (9.81; 1.85-52.04; P = .007) were significant.ConclusionsA significant percentage of Colombian patients fail to achieve remission of proliferative lupus nephritis after six months of treatment.     

Juvenile lupus: Different clinical and serological presentations compared to adult lupus in Egypt

Aim of the work: We aimed to evaluate the differences in clinical presentation, serological pattern and disease activity between juvenile and adult-onset of Egyptian systemic lupus erythematosus (SLE) patients. Patients and methods: 160 Egyptian SLE patients (80 Adult-onset and 80 juveniles) were included. Patients records were reviewed for clinical and laboratory evaluation on presentation. Disease activity at onset was assessed using SLE Disease Activity Index (SLEDAI). Results: The mean age of the adult patients was 29.9 ± 7.2 years and of the juvenile cases (12.8 ± 2.1 years). The female:male ratio of the adults was 10:1 while it was 39:1 in the SLE children. The most common clinical presentation among adult SLE was malar rash (75%) followed by articular manifestations (62.5%), while in juveniles, nephritis (78.8%) followed by articular manifestations (71.2%) were the most common. Juvenile patients had more frequent neuropsychiatric (p = 0.015) and hematologic abnormalities (p < 0.001) at onset; and lupus nephritis (72.5%) compared to adults (36.2%) (p < 0.001) during the first year of presentation. Juvenile SLE showed higher frequency of proteinuria (p < 0.001), hematuria (p = 0.02) and active urinary sediments (p = 0.016). Proliferative nephritis was the most common form among both juveniles and adults. Positivity and titres of both anticardiolipin antibodies and lupus anticoagulant were significantly higher in juvenile SLE. Juvenile SLE patients had significantly higher SLEDAI [median (IQR): 12 (10–22)] compared to adults [median (IQR): 8 (4–12)], p < 0.001. Conclusion: Juvenile SLE patients differ from adult SLE with more frequent major organs affection and significantly higher serological activity. Earlier and more careful assessment with strict management plan and follow-up are needed in juvenile SLE patients.     

Transferrina y ceruloplasmina en orina de pacientes con lupus eritematoso sistémico. ¿Son útiles para diferenciar pacientes con nefritis lúpica?

Background and objectiveDiagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not.Materials and methodsSystemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created.ResultsThe study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8 ± 12.1 years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4 ± 8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good.ConclusionsIn our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.     

Urinary podocalyxin and nephrin levels as biomarkers in lupus nephritis patients: Relation to renal involvement and disease activity

Aim of the workTo evaluate the impact of systemic lupus erythematosus (SLE) on urinary levels of podocalyxin and nephrin and to determine their relationship to renal biopsy and disease activity in lupus nephritis (LN) patients.Patients and methodsThe study included 50 LN patients with their renal biopsy classified according to the international society of nephrology. Disease activity was determined using the British Isles Lupus Assessment Group (BILAG). All patients underwent clinical and laboratory evaluation. Urine samples were collected for the assessment of urinary podocalyxin (UPx) and nephrin (UN) by ELISA and for the estimation of protein (UP) and creatinine (Cr) concentrations. The UPx:Cr, UN:Cr and UP:Cr ratios were calculated.ResultsUrinary levels of podocalyxin (593.8 ± 282.2 ng/ml), nephrin (304.1 ± 236.8 ng/ml) and protein (2.36 ± 0.56 g/l) were significantly higher, while urinary creatinine levels (101.4 ± 28.7 mg/l) lower in LN patients compared to control (38.1 ± 9 ng/ml, 19.2 ± 4.1 ng/ml, 0.34 ± 0.13 g/l and 155.4 ± 26.7 mg/l; p = 0.0008, p = 0.0003, p = 0.00002 and 0.0009, respectively). Consequently, UNCr, UPxCr and UPCr ratios were significantly higher in patients compared to control. There was a significant correlation of the estimated ratios with the LN class and with the BILAG scores being most significant with UPx:Cr ratio. ROC curve and regression analyses defined UPx:Cr ratio as the specific significant predictor of pathological LN grade.ConclusionSLE deleteriously affects fine glomerular structure as reflected by increased urinary levels of podocyte-related proteins; podocalyxin and nephrin. Urinary podocalyxin/creatinine ratio significantly predicts the pathological impact of SLE on the kidney and could be used as a non-invasive marker for such effect and its progression.     

Correlation Between Quantitative Anti-dsDNA Levels with Severity of Proteinuria in Systemic Lupus Erythematosus Patients

ObjectiveTo evaluate the correlation of quantitative anti-dsDNA level with proteinuria levels in patients with lupus nephritis in a tertiary care hospital.Study designIn this prospective cross-sectional study, 76 patients of newly diagnosed SLE coming to Fatima Memorial Hospital were included in the study period between January 2020 to June 2020. Demographic data such as age, gender, lupus manifestations such as serositis, arthritis, mucocutaneous disease, and neuropsychiatric manifestations were recorded. Quantitative anti-dsDNA was measured by enzyme-linked immunosorbent assay and proteinuria was estimated by 24 h urinary protein collection. Data was analyzed by SPSS 23. Association between categorical variables was assessed using chi-square test. For comparison of categorical independent and continuous dependent variable t-test or Mann–Whitney U test was applied.ResultsThe median age of the cohort was 29 (with inter quartile range – IQR – of 13) years. The female gender comprised of 68 (89.4%) of the cohort population. The median anti-dsDNA level was 54.9 (183.6 IQR) IU, and baseline proteinuria of the cohort was 520 mg/dL (1.49 IQR). There was a significant association of anti-dsDNA level with systemic features such as arthritis (p = <0.01), serositis (p = <0.01) and, Raynaud's phenomenon (p = <0.01). NPSLE and mucocutaneous features did not show statistically significant association (p = 0.91 and 0.14 respectively). Baseline anti-dsDNA showed a statistically significant correlation with baseline proteinuria levels (p = <0.01).ConclusionQuantitative anti-dsDNA is directly correlated with nephritis measured as proteinuria, and can be detected even before organ involvement. Hence, it can determine disease course and guide early treatment.     

Tumor necrosis factor-α, its related immunoregulatory long non-coding RNA (THRIL) and micro-RNA 145 as potential biomarkers in lupus nephritis patients

Aim of the workTo explore the differential expression of tumor necrosis factor-α (TNF-α), its related immunoregulatory long non-coding RNA (THRIL), and microRNA145 (MIR145) in systemic lupus erythematosus (SLE) patients and their diagnostic utility in lupus nephritis (LN).Patients and methodsThe study included 60 SLE patients; 30 with LN, 30 without LN (NN), and 30 matched controls. SLE disease activity index was assessed. Serum TNF-α level was determined by enzyme linked immunosorbent assay. Serum fold change (FC) in expression of THRIL and MIR145 were assayed by real time polymerase chain reaction.ResultsThe patients mean age was 32.6 ± 6.8 years and were 52 females and 8 males (F:M 6.5:1). Serum TNF-α level was significantly higher in SLE patients (108.6 ± 47.8 pg/ml) compared to control (39.6 ± 3.7 pg/ml) (p < 0.001). THRIL expression was upregulated (8.3 ± 6.9 vs. 1.02 ± 0.06 FC, p < 0.001) and MIR145 downregulated (0.39 ± 0.36 vs. 0.92 ± 0.94 FC, p < 0.001) in SLE patients versus controls. THRIL correlated with disease activity (r = 0.27, p = 0.035) and MIR145 with C3 (r = −0.32, p = 0.04) and C4 (r = −0.36, p = 0.016) levels in SLE patients. In LN patients, TNF-α and THRIL were increased while MIR145 downregulated (p < 0.001 each) and proteinuria significantly correlated with TNF-α (r = −0.4,p = 0.028), THRIL (r = 0.48, p = 0.007) and MIR145 (-0.42, p = 0.02). In NN patients, TNF-α and THRIL (p < 0.001 both) were increased while MIR145 downregulated (p = 0.023). TNF-α (cutoff ≥ 122.5 pg/ml, AUC 0.67, p = 0.003), and MIR145 (cutoff ≤ 0.22 FC, AUC 0.71, p = 0.026) discriminated LN from NN. The combination of TNF-α and MIR145 discriminated better than either alone (AUC 0.75, p = 0.002).ConclusionTNF-α and MIR145 are potential biomarkers of LN in SLE.     

Expression of T helper 17 cells and interleukin 17 in lupus nephritis patients

Background

Modern data suggest that interleukin 17 (Il-17) and Il-17 producing cells play an important role in the pathogenesis of lupus nephritis (LN). It was reported that T helper 17 migrate to the kidney and contribute to inflammatory processes.