Lupus Nephritis Class Research Articles

#1505 Late-onset lupus nephritis: clinical-epidemiological, histological, prognostic and therapeutical implications: a single center experience

Abstract Background and Aims Systemic lupus erythematosus (SLE), a chronic autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women in fertile age. Late-onset SLE is defined as a disease onset over 50 years. Our main objective was to analyze the clinical, histological, prognostic and therapeutical features related to LN in our late-onset SLE population. Method A single center and retrospective study was performed comparing clinical-demographic, histological, prognostic and therapeutical data of 45 LN biopsied patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic-onset (< 45 years) and late-onset (> 45 years). Results Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis and higher SDI score. On histology they showed more non-proliferative LN classes (II followed by V). Late-onset LN responders needed more time to achieve response but had fewer relapses. Non responsive patients had more incidence of acute kidney injury (AKI) and more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, as well as more need for renal replacement therapy (RRT) at diagnosis and at follow-up. The principal independent variables associated with relapse were the younger age at SLE diagnosis and an initial partial renal response (PRR). Patients of both groups who experienced relapse received higher doses of intravenous cyclophosphamide and less mycophenolic acid (MFA) analogues. Patients who received induction with MFA analogues were more likely to achieve complete renal response (CRR) or non-renal response (NRR). Conclusion late-onset LN is often accompanied by poor renal function at presentation. It seems imperative to establish a tailored approach in this fragile population in order to avoid unnecessary immunosuppression.

#2817 Preliminary results of dapagliflozin in inactive lupus nephritis cross-over randomized trial

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD). Lupus nephritis (LN) patients in remission may continue with residual proteinuria due to scars and hyperfiltration. However, LN patients were excluded from the main trials with SGLT2 inhibitors. This trial aims to assess the effect and safety of dapagliflozin in inactive LN patients with residual proteinuria. Method For this cross-over randomized trial, we include adult patients with LN class III, IV (±V) without active nephritis but with proteinuria >500 mg/24 h or UPC > 200 mg/g and eGFR ≥ 20 ml/min, in the maintenance treatment with a RAAS and mycophenolate mofetil (<2g/day) in stable a dose for at least four weeks before the randomization. We excluded patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI>2), use of induction therapy in the last 12 months (cyclophosphamide, mycophenolate mofetil >2g/day and calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we excluded patients with recurrent urinary infections (>3 times/year). Those included were randomized to receive dapagliflozin 10 mg on top of standard of care therapy (SoC) or not. After 24 weeks the groups were switched and those without dapagliflozin received it for the next 24 weeks. Primary endpoint is reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints are sustained reduction of eGFR>30%; occurrence of hypotension symptoms; and number of infections on dapagliflozin treatment versus exclusive SoC therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05). Results From 97 screened class III, IV (± V) LN patients under maintenance therapy, we excluded 67 due to active nephritis, low proteinuria or low eGFR. We included 30 patients that were randomized 14 to start the treatment with dapagliflozin on top of SoC and 16 to remain with the usual therapy for 24 weeks. Six patients were excluded from the analysis due to new LN flare or lost to follow-up. We analyzed the data of 12 patients in the initial Dapa + SoC and 12 patients in the initial SoC group after 3 (n = 21), 6 (n = 18), 9 (n = 14) and 12 (n = 12) months. Patients in initial Dapa group had a significant decrease in proteinuria after 6 months (1159 to 882 mg/day; p = 0.017) but increased to 1105 mg/day 6 months after the drug withdrawal (Fig. 1A). This preliminary analysis shows a significant reduction in the proteinuria of –35.8% in patients after 6 mo of dapagliflozin as opposed to an increase in 7.2% for those in the SoC therapy at the end of a 6 mo period, p = 0.02 (Fig. 1C). The drug was well tolerated, but 4 (33.3%) of the patients reported hypotension symptoms during the first days of dapagliflozin. There was one case of urinary infection in each group, but in the same patient. Conclusion Preliminary results show a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without an increase in infections.

Neutrophils-derived Parameters as Cost-effective Inflammatory, Disease Activity Marker in Systemic Lupus Erythematosus (SLE) and Role in Prediction of Lupus Nephritis

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations and approximately 50% of the SLE patients develop lupus nephritis (LN), which increases the risk of renal failure, cardiovascular diseases and overall survival. Objectives: Evaluation of neutrophil-derived parameters (Neut-X, Neut-Y and Neut-Z) as an inflammatory, disease activity marker and as a predictor of nephritis in SLE patients. Material and Methods: In this cross-sectional study, 3 ml K3EDTA blood was taken from 110 SLE patients presented in Department of Clinical Immunology to evaluate neutrophil-derived parameters in Sysmex XT2000i haematology analyser and their correlation with other inflammatory biomarkers like, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as SLE disease activity index-2000 (SLEDAI-2K). 24-hours urine protein levels were also estimated as a marker of renal involvement. Records of renal biopsy were available in 73 SLE patients, who belonged to different morphologic classification of LN. Results: After performing bivariate Spearman correlation analysis (SPSS software, version 26.0), Neut-X (measures cytoplasmic granularity by side scattering) and Neut-Z (vector sum of Neut-X and Neut-Y) showed a significant positive correlation ( r > 0.200, P < .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r > 0.200, P < .05) with ESR and CRP. Receiver-operating characteristic curve analysis was used to evaluate diagnostic value of 24-hour urine protein and predictive values of neutrophil-derived parameters for renal involvement in SLE patients. Among neutrophil-derived parameters, Neut-X was found to be the best predictor of renal dysfunction with highest AUC of 0.710 (95% CI: 0.604-0.816; cut-off: 1344.50; sensitivity: 84.7%; specificity: 50%) followed by Neut-Z with AUC of 0.707 (95% CI: 0.600-0.813; cut-off: 1403.67; sensitivity: 87.5%; specificity: 50%). Conclusion: Our study shows that neutrophil-derived parameters may be used as novel cost-effective, non-invasive biomarker of disease activity as well as for predicting renal involvement in SLE patients.

Update on Lupus Nephritis

Lupus Nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE), impacting up to 40% of SLE patients. Despite advancements in understanding the pathogenesis of LN, outcomes have not significantly improved since the early 2000s. LN patients face higher mortality, emphasizing the importance of achieving disease remission. Screening for nephritis involves regular monitoring, especially within the first 5 years of SLE diagnosis. Monitoring includes urinalysis, serum creatinine, and immune serology. Kidney biopsy remains the gold standard for LN diagnosis and classification, providing crucial information for treatment decisions. The standard of care involves hydroxychloroquine for all LN patients, with immunosuppressive treatments tailored to the histologic class. The recently approved medications, belimumab and voclosporin, offer additional therapeutic alternatives. Approximately 20% of LN patients exhibit features of thrombotic microangiopathy, warranting anticoagulation. Optimizing glucocorticoid dosing is recommended, favouring lower doses to minimize adverse effects. Lifelong monitoring is essential, as flares can occur at any point, emphasizing the need for continued immunosuppression. Given the lack of renal response in 30–60% of patients, the addition of combination therapies, such as calcineurin inhibitors or belimumab, should be considered. Duration of treatment is crucial, considering the progressive loss of podocytes and nephron function, which may lead to chronic kidney disease. Regular monitoring, maintenance immunosuppression, and lifestyle modifications contribute to preventing flares and improving long-term outcomes for LN patients.

Predictive factors of developing lupus nephritis in systemic lupus erythematosus

Renal involvement is common in systemic lupus erythematosus (SLE), and even without elevated serum creatinine, there is a high proportion of abnormal urine analysis in these patients. Lupus nephritis (LN) develops early in the course of the disease in 50% of SLE patients, and end stage renal disease (ESRD) occurs in 4.3-10.1%. We performed a keyword-based literature search and included 31 articles published from 2004 to 2023. Ethnic and racial differences may affect LN, including higher incidence of LN in Black, Hispanic and Asian compared with white patients. In addition, male sex, longer disease duration, smoking, low albumin globulin ratio, low complement, anti-double stranded DNA, high anti-Sm is associated with disease progression to LN. High serum creatinine (>1.5 mg/dL) at disease onset is the most commonly reported independent clinical laboratory predictor for ESRD in patients with SLE. Other factors indicating an increased risk for ESRD are higher chronicity index, high systolic blood pressure, black race, male sex, hypocomplementemia, class of LN (III, IV and V) and older age.

Lupus Nephritis Outcomes after Stopping Immunosuppression.

Background/Objectives: Immunosuppression (IS) is a standard therapy for lupus nephritis (LN). Data on the outcomes of patients with LN after the discontinuation of immunosuppression remain uncertain. This study aimed to evaluate the outcomes and results of patients with lupus nephritis (LN) who ceased immunosuppressive (IS) therapy. Methods: Records were obtained on the clinical and laboratory features of LN patients who were treated at our Lupus Unit. They included median values and ranges for various numerical variables such as patient age, disease duration, and treatment duration. Categorical variables such as gender, LN class, IS treatment type, and patient outcomes, which were categorized as either "stable" or "flare experienced", were presented as percentages and frequencies. A flare in LN was characterized by a two-fold increase in serum creatinine levels and a rise in proteinuria following the cessation of IS medication. Results: Outcomes were assessed for 45 patients with LN who ceased IS therapy after achieving remission. The patients' median age was 55 years (29-78). The median duration of treatment was 4 years (0.5-14). The LN histology distribution was class V = 24.4%, class IV = 17.8 %, class III = 17.8%, class III + IV = 15.6%, class III + V = 6.7%, class IV + V = 2.2%, and class II + IV and II = 2.2%. At the discontinuation of IS treatment, creatinine levels were elevated in 9/45 (20%) patients. Furthermore, 28.9% of patients relapsed after IS treatment discontinuation. Patients with anti-Smith antibodies (anti-Sm) were observed to have a higher occurrence of relapses, with six patients experiencing flare compared to four patients who remained stable (p = 0.03). Five (38.5%) of the patients with flares had high creatinine levels after IS discontinuation. Conclusions: Most of our patients maintained clinical remission and stable levels of LN parameters after IS treatment discontinuation. Those with a high serum creatinine level, ongoing proteinuria, depleted complement levels, and the presence of anti-Sm antibodies were more likely to experience flares after the discontinuation of IS therapy.

Maternal and fetal outcomes in pregnancy complicated by pre-existing lupus nephritis: Insights from a developing country Pakistan.

Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12months after child birth. The mean maternal age at SLE diagnosis was 21.45 ± 6years and at first pregnancy was 26.49 ± 5.63years. The mean disease duration was 14.02 ± 19.8months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12months. The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

Serum myeloperoxidase level as A marker of activity in patients with systemic lupus erythematosus with lupus nephritis class III and IV

Serum myeloperoxidase level as A marker of activity in patients with systemic lupus erythematosus with lupus nephritis class III and IV

Renal Manifestation of Mixed Connective Tissue Disease

A young female presented with facial puffiness and swelling in both lower limbs for 3 months, distension of the abdomen, and breathlessness on exertion for 1 month with a history of hypertension and hypothyroid on regular treatment. On general physical examination, there were pallor, bilateral pitting edema, tachycardia, and blood pressure of 190/100 mmHg. Abdominal examination revealed shifting dullness. Respiratory and cardiovascular systems were normal. Fundoscopy revealed Grade 1 papilledema, and the rest of the neurological examination was unremarkable. Investigations showed normocytic normochromic anemia, serum creatinine of 1.6 mg/dl, and hypoalbuminemia; urine R/E showed significant proteinuria; and anti-U1 ribonucleoprotein particle antibodies were positive. Two-dimensional echocardiography showed mild concentric left ventricular hypertrophy and mild pericardial effusion. Ultrasonography abdomen showed bilateral renal parenchymal disease and moderate ascites. Renal biopsy revealed diffuse proliferative glomerulonephritis and lupus nephritis Class IV. Renal manifestation is very rare in mixed connective tissue disease as an initial presentation.

Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney

BackgroundMacrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters.MethodsUsing immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients.ResultsThe frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease.ConclusionAlthough M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.

Renal arterial resistive index as a prognostic marker in lupus nephritis patients

IntroductionLupus nephritis (LN) is known to be one of the most serious complications of SLE and it is a major predictor of poor prognosis. Despite the improvement in understanding the pathophysiology of lupus nephritis and greater improvement in diagnostic approaches, lupus nephritis patients have poorer outcomes. ObjectivesStudy the relation between renal resistive index (RRI) and renal function and histopathological parameters in lupus nephritis (LN) patients. Also to investigate the usefulness of RRI in predicting response to treatment. Patients and methodsThis study included 126 patients who were split into two groups (group 1: 101 LN patients and group 2: 25 SLE patients without renal affection); and 100 healthy controls (group 3). The RRI was measured for all participants through a colored Doppler ultrasound examination. LN patients underwent renal biopsy and received their therapy and were followed up for 6 months. ResultsThe RRI was significantly greater in the LN group (mean±SD; 0.64±0.07) than in SLE patients without nephritis (0.5884±0.04) (P<0.0001). The RRI was greater in LN class IV (P<0.0001). RRI significantly correlated with the chronicity index (r=0.704, P<0.0001), activity index (r=0.310, P=0.002), and serum creatinine (r=0.607, P<0.0001) and negatively correlated with eGFR (r=−0.719, P<0.0001). Almost eighty-five percent (84.8%) of LN patients responded to induction therapy. RRI was significantly greater in the nonresponder group (mean±SD, 0.73±0.02) than that in the responder group (0.63±.07) (P<0.0001). All non-responders to induction therapy while only 29.8% of responders had an RRI of ˃0.7. RRI, according to regression analysis was a significant predictor of response to treatment in LN patients. ConclusionRRI was significantly greater in the LN group and significantly correlated with kidney function and histopathological parameters. RRI can predict response to induction therapy in LN patients.

Lupus Nephritis: A Literature Review

Systemic lupus erythematosus (SLE) has diverse clinical presentations, including lupus nephritis (LN), if LN manifest the mortality &amp; morbidity will be elevated. The majority of SLE cases found in females, especially during puberty and childbearing age. A comprehensive understanding of the epidemiology, classification, diagnosis, and management of LN is essential for medical practitioners. Initially, the diagnostic process requires clinical examinations to find clinical manifestations. This process then followed by laboratory assessments to diagnose SLE and identify any indication related to kidney damage, commonly proteinuria. Other findings such as haematuria and leukocyturia may also present. Antinuclear antibodies (ANA) test and anti-dsDNA serves as primary diagnostic tool. In addition, kidney biopsy is the gold standard for LN due to its ability to confirm and measure the stadium for treatment guide. The therapy is specifically based on clinical and biopsy findings, categorized by World Health Organization (WHO) into five classes, namely normal, mesangial, focal and segmental proliferative, diffuse proliferative, and membranous. Accurate diagnosis in the initial stage and suitable therapy is crucial to significantly improve the prognosis of LN. In this review, we address some clinical manifestations related to LN and standardised diagnostic assessment tools, with an ultimate goal to improve the outcome of patients with lupus through an individual-specific management.

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Influence of Podocyte Injury on the Development of Class IV Lupus Nephritis.

In the kidneys, Systemic Lupus Erythematosus leads to Lupus Nephritis (LN), a form of glomerulonephritis. There is evidence that patients with LN may present activation of specific pathways for podocyte injury. This injury can occur through different mechanisms such as loss of podocyte adhesion to the glomerular basement membrane, cell death or dedifferentiation. Podocyturia with consequent podocytopenia has been described in some nephropathies such as LN, highlighting the importance of studying podocyte injuries in this condition. Evaluating in situ morphological characteristics of podocytes becomes relevant for a better understanding of the processes involved in their pathogenesis. This study investigated podocytes in different classes of LN in renal biopsies performed by the Kidney Research Center at the Federal University of Triângulo Mineiro. Twenty control cases and 29 biopsy cases diagnosed with LN were selected, divided according to the histopathological classes of the disease. Podocyte density was assessed through immunohistochemistry for Wilms tumor 1 protein and the evaluation of foot process effacement was performed by transmission electron microscopy. Podocyte density was lower in the LN and this reduction was observed in all analyzed classes when compared to the control group. More foot process effacement was observed in the LN group, with more effacement in classes I/II and class IV compared to the control group. The class IV group showed more foot process effacement than the class III group and presented higher proteinuria levels compared to the classes I/II group. A strong, positive, and significant correlation was observed between the activity index and foot process effacement in the class IV group. Podocytes play an important role in the development of LN, and possibly, injuries to these cells are more closely related to the inflammatory/diffuse proliferative cellular process developed in class IV LN.

Association of Mitochondrial Pyruvate Carrier with the Clinical and Histological Features in Lupus Nephritis.

Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN. Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student's t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman's rank correlation. Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index. Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.

Factors influencing self-management behaviors in persons with lupus nephritis: A cross-sectional study.

Patients with lupus nephritis experience disease symptoms and side effects from treatment. Although self-management behaviors are important in patients with this disease, there is limited research on the factors influencing these behaviors. This study aimed to examine the factors influencing self-management behaviors in patients with lupus nephritis. This cross-sectional study was conducted in 240 patients with lupus nephritis at a university hospital in Thailand between August 2019 and December 2020 using a random sampling method. Data were collected using a demographic and clinical characteristic questionnaire, Self-Management Behavior Questionnaire, Self-efficacy for Managing Chronic Disease: A 6-item Scale, Knowledge about Lupus Nephritis Questionnaire, Family Support Scale, Social Networks in Adult Life Questionnaire, and Memorial Symptom Assessment Scale for Lupus Nephritis. Descriptive statistics and multiple linear regression analyses were employed. The participants reported a moderate level of self-management behaviors. Multiple regression analyses revealed that disease duration, income, symptoms, self-efficacy, knowledge, family support, social networks, and classes of lupus nephritis significantly explained 21% of the variance in self-management behaviors (R2 = 0.21; F(8,231) = 7.73; p <0.001). Family support (β = 0.32, p <0.001) and symptoms (β = -0.23, p <0.001) were significant determinants of self-management behaviors in patients with lupus nephritis. The findings provide valuable insight for nurses to better understand the factors influencing self-management behaviors in patients with lupus nephritis. Patients with low family support and high symptom severity may face difficulty in performing self-management behaviors. Nurses should pay more attention to these patients and provide family-based interventions to optimize self-management behaviors in this population.

The role of urinary biomarker monocyte chemoattractant protein (MCP-1) in correlation with different histopathological classes of lupus nephritis in Egyptian patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was &gt;245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity.

Clinicopathological Assessment of Modified Activity and Chronicity Indices in Lupus Nephritis at a Teaching Hospital in Mysore, India

Introduction: In 20-49% of patients with Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN) is a major complication and, therefore, an important prognostic determinant of SLE. The Activity and Chronicity Indices (AI and CI), used as adjuncts to the histological classification of LN, assist in identifying patients who will benefit from immunosuppressive therapy. Aim: To investigate the correlation of AI and CI in patients with biopsy-proven LN with clinical and laboratory findings. Materials and Methods: A cross-sectional study was conducted as the Departments of Pathology and Nephrology, JSS Medical College and Hospital Mysore, India from January 2023 to March 2023, by retrieving the data of 56 patients with biopsy proven LN. AI and CI were assessed and classified. Data from multiple groups were compared using Pearson’s chi-square test, and between two groups using independent samples t-test with Statistical Package for Social Sciences (SPSS) version 21.0. Pearson’s correlation coefficient (r-value) was calculated using Microsoft excel 2021. Results: Renal biopsies from 56 cases with biopsy-proven LN were studied, with a mean age of 28±10.30 years and a M:F ratio of 1:10.2. Of the 56 biopsies studied, active lesions were seen in 47 (83.9%) and chronic lesions in 21 (37.5%). AI showed statistical significance with hypertension (p=0.049) and haematuria (p=0.005), with proteinuria (p=0.001, r=0.72), serum creatinine (p=0.037, r=0.62), and blood urea nitrogen (p=0.003, r=0.55) showing a statistically significant positive correlation. CI showed a statistically significant positive correlation with proteinuria (p=0.028, r=0.039) and serum creatinine (p=0.010, r=0.58). Both AI and CI showed statistical significance with the degree of renal insufficiency, with CI (p=0.008) displaying a stronger statistical significance than AI (p=0.012). Conclusion: In conclusion, the management and prognosis of patients with suspected LN are greatly facilitated through information obtained from renal biopsy, especially AI and CI, which are useful guides to treatment. It is important to study renal biopsy for the constellation of features in LN for better patient management.

Identification of driver genes in lupus nephritis based on comprehensive bioinformatics and machine learning.

Lupus nephritis (LN) is a common and severe glomerulonephritis that often occurs as an organ manifestation of systemic lupus erythematosus (SLE). However, the complex pathological mechanisms associated with LN have hindered the progress of targeted therapies. We analyzed glomerular tissues from 133 patients with LN and 51 normal controls using data obtained from the GEO database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key gene modules. The least absolute shrinkage and selection operator (LASSO) and random forest were used to identify hub genes. We also analyzed immune cell infiltration using CIBERSORT. Additionally, we investigated the relationships between hub genes and clinicopathological features, as well as examined the distribution and expression of hub genes in the kidney. A total of 270 DEGs were identified in LN. Using weighted gene co-expression network analysis (WGCNA), we clustered these DEGs into 14 modules. Among them, the turquoise module displayed a significant correlation with LN (cor=0.88, p<0.0001). Machine learning techniques identified four hub genes, namely CD53 (AUC=0.995), TGFBI (AUC=0.997), MS4A6A (AUC=0.994), and HERC6 (AUC=0.999), which are involved in inflammation response and immune activation. CIBERSORT analysis suggested that these hub genes may contribute to immune cell infiltration. Furthermore, these hub genes exhibited strong correlations with the classification, renal function, and proteinuria of LN. Interestingly, the highest hub gene expression score was observed in macrophages. CD53, TGFBI, MS4A6A, and HERC6 have emerged as promising candidate driver genes for LN. These hub genes hold the potential to offer valuable insights into the molecular diagnosis and treatment of LN.

The Inflammatory and Oxidative Status of Newly Diagnosed Class III and Class IV Lupus Nephritis, with Six-Month Follow-Up.

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.