Systemic Lupus Erythematosus: A Review.

Importance: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems. Approximately 3.4 million people worldwide have received a diagnosis of SLE. Observations: Approximately 90% of people with SLE are female. Although there are no uniformly accepted diagnostic criteria for SLE, the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE. These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis; and immunologic measures, such as SLE-specific autoantibodies and low complement levels. Approximately 40% of people with SLE develop lupus nephritis, and an estimated 10% of people with lupus nephritis develop end-stage kidney disease after 10 years. The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications. Treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity. Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality. Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease. Three SLE medications were recently approved by the Food and Drug Administration: belimumab (for active SLE in 2011 and for lupus nephritis in 2020), voclosporin (for lupus nephritis), and anifrolumab (for active SLE). Conclusions and Relevance: Systemic lupus erythematosus is associated with immune-mediated damage to multiple organs and increased mortality. Hydroxychloroquine is first-line therapy and reduces disease activity, morbidity, and mortality. When needed, additional immunosuppressive and biologic therapies include azathioprine, mycophenolate mofetil, cyclophosphamide, belimumab, voclosporin, and anifrolumab.

The relationship between the modified National Institute of Health activity and chronicity scoring system, and the long-term prognosis for lupus nephritis: A retrospective single-center study.

BACKGROUND: The revision of International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification guidelines for lupus nephritis (LN) was suggested by a working group, who recommended a modified National Institute of Health (NIH) activity and chronicity scoring system to evaluate active and chronic LN lesions. However, whether this approach was useful for estimating long-term prognosis for LN patients is unclear. METHODS: We conducted a retrospective cohort study in Japanese subjects with biopsy-proven LN, between 1977 and 2018. Pathologic lesions were evaluated based on ISN/RPS 2003 classifications and the modified NIH scoring system. Patients were grouped by activity index (low, 0-5; moderate, 6-11; high, 12-24), and chronicity index (low, 0-2; moderate, 3-5; high, 6-12). The primary outcome was a composite of end-stage kidney disease (ESKD) or all-cause death, and the secondary outcome was ESKD alone. RESULTS: Sixty-six subjects with a median age of 31 years were included. During median follow-up (11.5 years), 15 patients reached the primary outcome: 10 had ESKD, four had died, and one had ESKD and died. Kaplan-Meier analysis showed that the cumulative primary outcome incidence increased with a higher chronicity index (log-rank trend p < 0.001). From multivariable survival analysis, moderate (hazard ratio [HR] 6.17, 95% confidence interval [CI] 1.14 to 33.20; p = 0.034) and high chronicity indices (HR 20.20, 95% CI 1.13 to 359.82; p = 0.041) were risk factors for the primary outcome. CONCLUSION: Moderate and high chronicity indices were associated with an increased ESKD risk for LN.

Clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with lupus nephritis.

OBJECTIVE: We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). METHODS: Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. RESULTS: Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare (P < 0.05, for both). VCAM-1 level correlated with proteinuria, serum creatinine, and anti-dsDNA antibodies, and inversely correlated with C3. VCAM-1 level also correlated with leukocyte infiltration and fibrinoid necrosis/karyorrhexis scores in active LN kidney biopsies. ICAM-1 level correlated with proteinuria, but not anti-dsDNA or C3, nor histopathological features. VCAM-1 level increased 4.5 months before renal flare, while ICAM-1 increase coincided with flare, and both decreased after treatment. ROC analysis showed that VCAM-1 distinguished active LN from healthy subjects, LN in remission, active non-renal lupus, and CKD (ROC AUC of 0.98, 0.86, 0.93 and 0.90 respectively). VCAM-1 level in combination with either proteinuria or C3 was superior in distinguishing active LN from remission compared to the measurement of individual markers. Serum ICAM-1 level distinguished active LN from healthy subjects and LN patients in remission (ROC AUC of 0.75 and 0.66 respectively), but did not distinguish between renal versus non-renal lupus. ICAM-1 level in combination with markers of endothelial cell activation (syndecan-1, hyaluronan and thrombomodulin) was superior to proteinuria, anti-dsDNA, or C3 in distinguishing active LN from quiescent disease. CONCLUSION: Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.

Downregulated Serum Exosomal miR-451a Expression Correlates With Renal Damage and Its Intercellular Communication Role in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

Association of the STAT4, CDKN1A, and IRF5 variants with risk of lupus nephritis and renal biopsy classification in patients in Vietnam.

BACKGROUND: Lupus nephritis is a common complication of systemic lupus erythematosus (SLE, OMIM #15200) in the Asian population and a main contributor to mortality and morbidity. In this study, we evaluate the variants on three genes STAT4, CDKN1A, and IRF5 and their association with lupus nephritis. METHOD: One hundred fifty-two SLE patients with confirmed lupus nephritis (through biopsy) and 76 healthy controls were recruited. Genotyping of SNPs on three gene STAT4, CDKN1A, and IRF5, phenotypic, and laboratory assessment were performed; renal biopsy and classification were carried out for the patient group. RESULTS: Carriers of rs7582694 C alleles on STAT4 have higher risk of lupus nephritis (OR 2.0; 95% CI [1.14, 3.19]; p = 0.015), at higher risk of hematuria and higher serum level of dsDNA antibodies compared to controls (p < 0.05) and were more likely to have nephrotic histopathology grading of class III or higher. No association was observed for CDKN1A; and no variation was observed for the IRF5 gene in both the study and control group. CONCLUSION: This study investigates the relationship between STAT4, CDKN1A, and IRF5 gene and SLE in a Vietnamese patient population. Patients with the C allele (STAT4) in rs7582694 were associated with a more severe disease phenotype.

Revised ISN/RPS 2018 classification of lupus renal pathology predict clinical remission.

BACKGROUND: A precise description of renal histological lesions and an appropriate classification of lupus nephritis are both essential for nephrologists to guide treatment and predict prognosis among patients. The prognostic value of ISN/RPS 2003 classification is controversial. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. OBJECTIVE: The study aimed to evaluate the predictive value of the clinical and pathological factors according to ISN/RPS 2018 classification on renal remission among patients with proliferative lupus nephritis. METHODS: A total number of 41 patients with proliferative lupus nephritis on adequate renal biopsy specimen between 2017 and 2018 were included. Clinical and histological variables were tested for their association with renal remission. Univariate and multivariate logistic regression analysis were performed to identify independent predictors of renal remission after 24 weeks of induction therapy. RESULTS: After induction therapy, 56.1% of patients reached complete and partial remission and 43.9% reached no remission. In univariate analyses, baseline glomerular filtration rate (GFR), presence of anti-DNA titer, cellular crescents, interstitial inflammation, glomerulosclerosis, interstitial fibrosis, tubular atrophy and total chronicity index strongly impacted renal response. After multivariate logistic regression analysis, we identified aging, presence of cellular crescents, and high total renal chronicity index as independent predictors of renal remission. Receiver operating characteristic (ROC) analysis revealed that baseline estimated GFR (AUC = 0.708; 95% CI 0.527-0.888), anti-DNA titer (AUC = 0.674; 95% CI 0.491-0.858), cellular crescent (AUC = 0.750; 95% CI 0.585-0.915) and renal chronicity index (AUC = 0.765; 95% CI 0.585-0.915) predicted renal remission. Combining all factors achieved a perfect score predicting renal response (AUC 0.924; 95% CI 0.840-1.000). CONCLUSION: The study identified baseline GFR, anti-DNA titer, cellular crescent, and high chronicity index according to revised ISN/RPS 2018 classification as important predictors of renal response after induction therapy in proliferative lupus nephritis.

The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

Lupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification-including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels-and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.

Resolution of huge thrombi in bilateral ventricles caused by severe lupus cardiomyopathy.

Ventricular thrombus is an uncommon, severe condition with high morbidity and mortality. Simultaneous left and right ventricular thrombi caused by lupus myocardiopathy have not been previously reported in the literature. This case presents a 42-year-old woman who has bilateral ventricular thrombi with reduced left ventricular ejection fraction (35.4%) and acute kidney injury. Pro-brain natriuretic peptide was >35000 pg/mL. Systemic lupus erythematosus was confirmed based on multiorgan injuries including malar rash, anemia, renal injury, positive antinuclear, anti-Smith antibodies, and decreased complements. Renal biopsy revealed lupus nephritis class III + V. Low molecular weight heparin, steroids, and mycophenolate mofetil were initiated, after which the patient experienced transient numbness in the right limbs and hemoptysis. She then recovered quickly and improved significantly with recovery of left ventricular systolic function (left ventricular ejection fraction 46%) and the eventual disappearance of thrombi. Simultaneous left and right ventricular thrombi are rare but life-threatening condition, prompting consideration of myocardiopathy caused by autoimmune diseases such as lupus. Timely treatment with immunosuppressants and anticoagulants may resolve the thrombi and improve cardiac function.

Electron microscopy study of 496 cases of lupus nephritis: A single-center experience.

INTRODUCTION: Renal involvement is seen in about 40-82% of systemic lupus erythematosus (SLE) Asian patients. The exact diagnosis and classification of lupus nephritis are important for treatment and prognosis. This study aimed to investigate the value of electron microscopy (EM) in the diagnosis and classification of lupus nephritis compared with light microscopy. METHOD: In this cross-sectional referral-center 16-year study of lupus nephritis, the final diagnosis was based on the EM study. Primary light microscopy findings were compared with EM diagnosis. Moreover, Immunofluorescence patterns distribution was assessed. RESULTS: From 496 patients diagnosed with lupus nephritis based on EM, 225(45.4%) of patients were categorized in class IV, followed by 98(19.7%), 93(18.8%), 46(9.3%), and 14(2.8%) who were categorized into classes of II, III, V, and VI respectively. Only 1(0.2%) patient belonged to class I, and 19(3.8%) cases were diagnosed with mixed two classes. Using EM was essential for diagnosing 25.6% of cases taking the correct classification by light microscopy into account; however, disregarding correct classification, this could change to a 7.4% contribution rate of EM. The most common cause of misdiagnosis, disregarding incorrect classification, was inadequate or wrong tissue. Positive associations were detected between tubular atrophy and interstitial fibrosis of both electron and light microscopy with different classes (P < 0.001). CONCLUSION: While light microscopy is highly accurate for diagnosing lupus nephritis regardless of correct classification, EM contributes substantially to the correct classification of lupus nephritis types.

Assessing outcomes in a lupus nephritis cohort over a 40-year period.

OBJECTIVES: To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 years after LN diagnosis. METHODS: An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975-1985 (D1), 1986-1995 (D2), 1996-2005 (D3) and 2006-2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome. RESULTS: Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades. CONCLUSION: Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.

Classifying and diagnosing systemic lupus erythematosus in the 21st century.

The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on molecular approaches and the results from large studies using polyomics may be interpreted as demonstrating the relevance of the genetic and environmental background rather than splitting SLE into several entities. In fact, an association study within the EULAR/ACR classification criteria project found associations between manifestations only within organ domains. This independency of various organ manifestations argues for SLE as one disease entity. The current review article will therefore concentrate on the clinical and immunological manifestations of SLE and on what we have already learned in this century. Moreover, the structure and essential rules of the EULAR/ACR 2019 classification criteria will be discussed. While classification and diagnosis are distinct concepts, which have to remain clearly separated, information derived from the process towards the classification criteria is also useful for diagnostic purposes. Therefore this article also tries to delineate what classification can teach us for diagnosis, covering a wide variety of SLE manifestations.

Lupus nephritis: clinical presentations and outcomes in the 21st century.

Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.

Pediatric lupus nephritis - An evil cousin of its adult counterpart: A single-center based experience from a tertiary care hospital of Eastern India.

CONTEXT: Systemic lupus erythematosus is an autoimmune multisystem disease with a high predilection for renal involvement. Lupus nephritis develops in 20% to 75% within the first two years. Presentation varies from subnephrotic proteinuria to end-stage renal disease. AIMS: To study clinical features, biochemical, and serological parameters and correlate with histological activity and chronicity score [modified National Institute of Health (NIH) score]. SETTINGS AND DESIGN: Retrospective, cross-sectional, single-center based study in a tertiary care hospital of Eastern India. SUBJECTS AND METHODS: We incuded 36 children with lupus nephritis diagnosed from February 2018 to March 2019. Laboratory data included were complete blood count (CBC), blood glucose, urine analysis, serum urea, creatinine, blood urea nitrogen (BUN), albumin, cholesterol, HBsAg, antihepatitis C virus (HCV) antibody, antistreptolysin O (ASO) titer, antinuclear antibody (ANA), myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA), proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA), double-stranded DNA (dsDNA), C3, and C4. Clinical parameters were age, sex, blood pressure (BP), skin lesions, arthralgia, edema, obesity. Renal biopsies examined with light microscopy, hematoxylin and eosin (H and E), periodic acid-Schiff (PAS), silver methanamine, Masson's trichrome (MT) stains. Immunofluorescence microscopy done with IgG, IgM, IgA, C3c, C1q, kappa, lambda antibodies. STATISTICAL ANALYSIS USED: Kruskal-Wallis and χ2 tests. RESULTS: Mean age was 15.12 ± 3.49 and 12.5 ± 1.73 years for lupus nephritis (LN) with activity and LN without activity, respectively. Mean dsDNA was higher and mean C3 was lower (52.35 ± 22.21 mg/dl) in active LN. Mean 24-hour urinary protein was higher in LN without activity. Serum creatinine was raised in active LN. LN class III and IV showed higher activity than chronicity. CONCLUSIONS: Pediatric LN is proliferative and more active as compared with adult counterparts. Activity scores are much higher than chronicity scores.

Clinical and histopathological features and short-term outcomes of lupus nephritis: a prospective study of 100 Egyptian patients.

OBJECTIVE: The short-term outcomes of lupus nephritis (LN) are variable and unpredictable among individuals. We aimed to evaluate the clinical and histopathological features and short-term renal outcomes in LN patients. METHODS: This was a prospective cohort study carried out at nephrology and rheumatology units in Egypt between 2018 and 2019. A total of 100 patients with biopsy-proven LN were studied. Patients were evaluated for response after six months. RESULTS: The female-to-male ratio was 8.1:1. About 70% of patients were hypertensive at disease onset, with rates for classes I, II, III, IV, V and VI LN being 1%, 7%, 20%, 53%, 14% and 6%, respectively. Among the immunosuppressive drugs used for induction, mycophenolate mofetil (MMF) represented the most commonly used (44%) followed by cyclophosphamide (CYC; 37%). After six months of follow-up, about two thirds of patients achieved remission. There was no significant difference in remission rate between MMF and CYC. On multivariate analysis, serum creatinine (SCr) at presentation was the most significant predictor of renal recovery. According to the receiver operating characteristic curve, the cut-off value of SCr was 1.6 mg/dL, with a sensitivity of 76% and specificity of 71% predicting renal recovery. Repeat renal biopsy was needed in 10 patients; class and treatment strategy changed in 40% and 70% of them, respectively. CONCLUSION: Our findings in Egyptian LN patients compare favourably with most studies.

A Validation of the 2018 Revision of International Society of Nephrology/Renal Pathology Society Classification for Lupus Nephritis: A Cohort Study from China.

BACKGROUND: A revision of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis has been published in 2018. The current study aimed to verify the utility of this system. MATERIALS AND METHODS: A total of 101 lupus nephritis patients from a large Chinese cohort who underwent renal biopsy in Peking University First Hospital were reevaluated by 2 renal pathologists, who had no knowledge of the clinical findings. The association between clinical data at the time of initial renal biopsy and follow-up and pathological features were further analyzed on all patients selected. RESULTS: The mean age of the cohort was 33 years with a male/female ratio of 1:9, and a median follow-up period of 128 months. The presence and extent of mesangial hypercellularity, endocapillary hypercellularity, global and segmental glomerulosclerosis, neutrophil exudation/karyorrhexis, glomerular hyaline deposits, extracapillary proliferation (crescents), tubular atrophy/interstitial fibrosis, and interstitial inflammation were significantly correlated with several clinical renal injury indices (systemic lupus erythematosus disease activity index, serum creatinine value, proteinuria, and C3 level) at the time of biopsy. By multivariable Cox hazard analysis, fibrous crescents, tubular atrophy/interstitial fibrosis, and the modified National Institutes of Health chronicity index were independent risk factors for patients' composite renal outcomes (hazard ratio [HR] 4.100 [95% CI 1.544-10.890], p = 0.005; HR 8.584 [95% CI 2.509-29.367], p = 0.001; and HR 3.218 [95% CI 1.138-9.099], p = 0.028; respectively). CONCLUSIONS: The 2018 revision of the ISN/RPS classification for lupus nephritis has utility for prediction of clinical renal outcomes.

Outcomes of membranous and proliferative lupus nephritis - analysis of a single-centre cohort with more than 30 years of follow-up.

OBJECTIVES: To compare membranous lupus nephritis (MLN) and proliferative lupus nephritis (PLN) with respect to survival, demographic, clinical and laboratory characteristics; and to investigate predictors of renal and patient survival. METHODS: Single-centre retrospective observational study. Patients with biopsy-proven PLN, MLN and mixed lupus nephritis were included. Groups were compared using appropriate statistical tests and survival was analysed through the Kaplan-Meier method. Cox regression analysis was performed to investigate predictors of renal and patient survival. RESULTS: A total of 187 patients with biopsy-proven lupus nephritis (135 with PLN, 38 with MLN and 14 with mixed LN) were followed for up to 42 years (median 12 years). There was a higher proportion of MLN amongst Afro-Caribbeans than amongst Caucasians (31% vs 15%, P = 0.010). Patients with MLN had significantly lower anti-dsDNA antibodies (P = 0.001) and higher C3 levels (P = 0.018) at diagnosis. Cumulative renal survival rates at 5, 10, 15 and 20 years were 91, 81, 75 and 66% for PLN and 100, 97, 92 and 84% for MLN, respectively (P = 0.028). Cumulative patient survival at 5, 10, 15 and 20 years was 94, 86, 80 and 76%, with no difference between PLN and MLN. Urinary protein-creatinine ratio above 42 mg/mmol and eGFR below 76 ml/min/1.73 m2, one year after the diagnosis of LN, were the strongest predictors of progression to end-stage renal disease. eGFR below 77 ml/min/1.73 m2, at one year, development of end-stage renal disease and Afro-Caribbean ethnicity were associated with higher mortality. CONCLUSION: Patients with MLN and PLN differ significantly regarding serological profiles and renal survival, suggesting different pathogenesis. Renal function at year one predicts renal and patient survival.

The predictive value of crescents in the disease progression of lupus nephritis based on the 2018 International Society of Nephrology/Renal Pathology Society Revision System: a large cohort study from China.

Objective: This study analyzed the associations of different crescents' fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system.Methods: A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed.Results: The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190-5.431; p = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326-6.313; p = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents.Conclusion: We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.

Wire-loop lesion is associated with serological immune abnormality, but not renal prognosis, in lupus nephritis.

BACKGROUND: Wire-loop lesion (WL) is one of the active lesions of lupus nephritis (LN). However, few reports have focused on the clinicopathological relationships of WL to serological immune abnormality and renal prognosis. METHODS: We enrolled 126 Japanese LN patients subjected to renal biopsy in 11 hospitals from 2000 to 2018. In patients with class III or IV of the International Society of Nephrology/Renal Pathology Society classification, we retrospectively compared clinicopathological findings between those with WL (WL+ group) and without WL (WL- group) to detect factors associated with WL. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2 for more than three months. We also compared these findings between those with CKD (CKD+ group) and without CKD (CKD- group) at the last visit to investigate factors associated with renal prognosis. RESULTS: Of 126 patients, 100 (79.4%) were classified as class III or IV. WL was found in 36 (36.0%) of them. Although the renal function did not differ, the WL+ group had a higher titre of serum anti-dsDNA antibodies and lower serum complement 3 levels than the WL- group. Linear regression analysis revealed a significant association only between anti-dsDNA antibodies and WL (ß = 0.27, 95% confidence interval (CI) 0.001-0.100, p = 0.01). Of these patients, 69 were tracked for 59.6 ± 55.1 months. Kaplan-Meier analysis showed no difference in renal prognosis between these groups. Next, the CKD+ group included 15 (22.1%) patients. They were older and had higher frequencies of hypertension and hyperuricaemia, serum creatinine (Cr) level, glomerulosclerosis, interstitial inflammation, interstitial fibrosis and tubular atrophy than the CKD- group at the time of renal biopsy. The frequency of WL was not significantly different. Cox regression analysis revealed significant associations of CKD with hypertension, hyperuricaemia, serum Cr level at the time of renal biopsy clinically and with tubular atrophy histologically. CONCLUSIONS: WL was associated with serum anti-dsDNA antibodies but not with renal prognosis, suggesting that WL reflects immune abnormality but is not an independent factor predictive of renal prognosis in LN.

Lupus Nephritis Class IV-Global Is Associated with a Higher Risk of End-Stage Renal Disease than Class IV-Segmental.

INTRODUCTION: The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) divides class IV into segmental and global (IV-S and IV-G) based on evidence suggesting different renal outcomes. However, subsequent studies have shown conflicting results. OBJECTIVE: This study was performed to compare long-term renal outcomes between the IV-S and IV-G classes. METHODS: This is a retrospective cohort study of adult patients with biopsy-proven class IV LN using the ISN/RPS classification. The primary end point was end-stage renal disease (ESRD). RESULTS: Among the 89 patients, rapidly progressive glomerulonephritis was twice as frequent in the IV-G group (60 vs. 29%; p = 0.005) than that in the IV-S group. Moreover, the IV-G group had a higher rate of biopsy with cellular and fibrocellular crescents (70.9 vs. 47.1%, p = 0.024) and more crescentic glomerulonephritis (34.5 vs. 5.8%, p = 0.007) than the IV-S group. After a mean follow-up of 57 months, the IV-G group had a greater risk of ESRD (RR 3.9; 95% CI 1.2-12.2, p = 0.006) than the IV-S group. Multivariate analysis indicated that class IV-G was an independent predictor of ESRD. CONCLUSIONS: Patients with class IV-G have a higher risk of ESRD than patients with class IV-S.