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This phase 3 multicenter, randomized, double-blind, placebo-controlled 2-year trial compared the efficacy and safety of intravenous belimumab with those of placebo, plus standard therapy, in patients with active lupus nephritis. More patients who received belimumab had a primary efficacy renal response than those who received placebo.

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD.ConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

ObjectivesTo investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).MethodsPatients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.ResultsSLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10–86 and OR 7.48 (6.73 to 8.32), p=2.2×10–304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10–5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10–2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10–5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10–3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10–2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10–3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10–2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10–3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10–2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10–2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10–2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10–7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10–3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10–2) in high to low quartile comparison.ConclusionsA high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.

BackgroundLupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis).MethodsWe conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected data on demographic, clinical, and laboratory characteristics, including histological findings, treatment modalities, and disease outcomes. Statistical analyses were performed to identify factors impacting LN development and prognosis.ResultsAmong 331 LN patients, early-onset was diagnosed in 207 (62.54%) and delayed-onset was documented in 122 cases (36.86%). In 2 (0.6%) LN cases, the time of first kidney manifestation in the SLE course was unknown. Delayed-onset LN had a higher female-to-male ratio and younger age at SLE diagnosis. This group was associated with more severe clinical manifestations. In turn, studied subgroups did not differ in internist comorbidities, kidney histopathology, and family history regarding autoimmune diseases. Delayed-onset LN exhibited a higher frequency of anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, and anti-cardiolipin IgG autoantibodies. During a 14-year follow-up period, 16 patients died. Mortality rate and causes of death were comparable in both analyzed subgroups.ConclusionsMore severe clinical manifestations in delayed-onset LN prompt strict monitoring of non-LN SLE patients to diagnose and treat kidney involvement early. Also, recognizing the higher frequency of autoantibodies such as anti-dsDNA or anti-Smith in delayed-onset LN underscores the potential value of autoantibody profiling as a diagnostic and prognostic tool.

Lupus nephritis (LN) presents with varied outcomes depending on the age at diagnosis. We aimed to evaluate long-term kidney survival across three age groups. Patients were categorized based on their age at lupus nephritis diagnosis: ≤18 years (childhood), >18 to <45 (adulthood), and ≥45 years (elderly). The three groups' CKD (eGFR <60 ml/min/1.73 m for at least 3 months) or death-free survival was estimated using Kaplan-Meier curves and compared with the log-rank test. To evaluate the independent prognostic role of age, adjusted for other predictors of chronic kidney disease (CKD) or death, we used multivariate Cox regression analysis. This retrospective cohort study analyzed 260 patients followed for a median of 14.8 years. Of them, 46 (17.7%) were <18, 173 (66.5%) >18 and <45, and 41 (15.8%) ≥45 years old. 46% of elderly vs. 32.6% of children and 24.3% of adults had acute kidney disease (AKD) at diagnosis (P=0.02). Children had more active SLE, whereas the elderly had more chronic damage and hypertension. At 5, 10, and 20 years, CKD or death-free survival rates were 95.3%, 92.5%, and 88.4% in children; 98.2%, 90.1%, and 82.6% in adults; and 87.5%, 67.8%, and 53.5% in the elderly, respectively. Survival in elderly patients was significantly worse compared with children and adults (P= 0.001), whereas survival rates between children and adults were comparable (P = NS). At multivariate analysis, when the chronicity index was excluded from the model, older age emerged as an independent predictor of CKD or death (relative risk, RR: 3.278; CI: 1.402-7.662; P=0.006), with AKD (RR: 2.930; CI: 1.674-5.130; P<0.001), arterial hypertension (RR: 3.692; CI: 1.844-7.389; P<0.001), SLICC >0 (RR: 1.824; CI: 1.155-2.881; P=0.01), and failure to achieve complete remission at 1 year (RR: 4.784; CI: 2.355-9.716; P<0.001). While children and adults demonstrate comparable long-term kidney survival, elderly patients face significantly worse outcomes due to advanced chronicity and systemic damage. These findings highlight the need for tailored interventions in late-onset LN. Older-onset LN, in fact, was an independent predictor of CKD or death together with AKD, arterial hypertension, SLICC >0, and no remission at 1 year.

To study the clinical, laboratory profile and outcome of juvenile Systemic Lupus Erythematosus (jSLE) patients at a tertiary care centre in South India. A retrospective review of the medical records of all jSLE patients visiting the Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, India from February 2017 to December 2023 was performed. The clinical characteristics, treatment and outcomes were recorded and tabulated. Seventy patients diagnosed with jSLE were included in the study. The female-to-male ratio was 4.4:1. Mean age at onset and delay in diagnosis were 120.1 (+/- 56.8) and 11.7 (+/- 22.7) months respectively. The median follow-up period was 13 months (range 4, 29 months). Nine patients presented with early onset SLE (< 5 years). Most common manifestations were constitutional symptoms (n = 56), followed by haematologic (n = 55), and mucocutaneous(n = 50) involvement. Immunological workup showed SLE-specific antibody positivity in 38 patients, hypocomplementemia in 40 patients, and anti-phospholipid antibody positivity in 13 patients. Mortality was observed in five patients with LN while there was no mortality in the non-nephritis group (p 0.004). C1q deficiency was the most common cause of monogenic lupus seen in 5/9 patients; protein kinase C delta (PRKCD) defect and chronic granulomatous disease (CYBB mutation) were seen in one patient each. We describe a large cohort of jSLE from Southern India. Lupus nephritis was noted in 35.7% of our cohort and had a direct correlation with mortality. 10% of patients had monogenic lupus. Serious infections were more frequent in patients with monogenic lupus.

The role of complement in the long-term renal survival of patients with lupus nephritis (LN) remains poorly understood. Recent studies suggest its potential impact; however, long-term data are lacking. This multicenter, observational, retrospective study aimed at investigating the influence of complement levels on long-term renal outcomes in LN patients. We evaluated whether isolated C3 hypocomplementemia (i-LowC3), defined as serum low C3 (≤80 mg/dL) and normal C4 (>10 mg/dL) six months after kidney biopsy is associated with subsequent risk of chronic kidney disease (CKD), End Stage Kidney Disease (ESKD) or death. 445 patients with LN were studied (median follow-up 4.9 years). Based on six-month C3/C4 levels, patients were categorized into i-LowC3 (91 patients) and controls (354 patients). Over the first six months, serum C3 and C4 levels increased by a median of 20 mg/dL and 5 mg/dL, respectively. i-LowC3 was significantly associated with twice the risk of a poor outcome, including CKD, ESKD, composite outcome of CKD or death and ESKD or death, with lower survival rates for all these outcomes compared to controls (P < 0.001). Multivariate Cox regression analysis revealed a lower risk of CKD and CKD or death with increases in C3 levels during the first six months, while i-LowC3 was associated with an independent higher risk for these outcomes. The trajectory of serum C3 levels within the first six months appears to predict long-term renal prognosis of LN patients. These findings support the use of i-LowC3 as a low-cost, readily available biomarker to guide early treatment of LN patients.

ObjectiveLupus nephritis (LN) is associated with a poorer prognosis in Latin American populations. However, the contributing risk factors contributing to this remain to be fully elucidated. This study aimed to develop a prognostic model for poor renal outcomes in patients of mestizo descent.MethodsWe conducted a multicentre, retrospective analysis including 290 adult mestizo patients with incident, biopsy-proven pure proliferative LN (International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV) from nine Chilean hospitals. Clinical, biological and histological variables were assessed. The primary outcome was a composite of stage IV/V chronic kidney disease, dialysis or death. Predictive variables were selected using multivariable Cox regression, and prognostic scores were derived accordingly. Internal validation was performed via bootstrapping. External validation included 93 Mexican patients, with model performance assessed using Harrel’s concordance index.ResultsTwo baseline factors were independently associated with poor renal outcome: estimated glomerular filtration rate <30 mL/min/m2 (HR 3.82, 95% CI 2.15 to 6.78; p<0.001) and histological chronicity index >2 (HR 2.01, 95% CI 1.18 to 3.43; p=0.01). Patients were stratified into three risk categories according to the presence of none (low risk), one (intermediate risk) or both (high risk) of these factors. The likelihood of the primary outcome increased progressively across these groups: high versus intermediate risk (HR 3.22, 95% CI 1.64 to 6.34; p=0.001), and intermediate versus low risk group (HR 2.41, 95% CI 1.35 to 4.30; p=0.003). The three-tier model was replicated in the validation cohort with a concordance index of 79% (95% CI 71% to 87%; p<0.001) between predicted and observed results.ConclusionsBased on two readily available features at the time of diagnosis, the proposed model effectively stratifies Latin American mestizo patients with pure proliferative LN (ISN/RPS class III or IV) into three risk categories for poor renal outcome. This tool may support improved risk-based management in this high-risk population.

The occurrence of lupus nephritis is primarily caused by the dysfunction of the autoimmune system, leading to the deposition of immune complexes (ICs) in the kidneys and associated inflammatory responses. Lymphocyte-related parameters, including the platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR), have been confirmed in recent years as important novel indicators for several inflammatory diseases. However, it remains unclear whether lymphocyte-related parameters can serve as prognostic indicators for lupus nephritis (LN). This study included a total of 143 LN patients, who were divided into several groups based on the optimal cutoff values of lymphocyte-related parameters. The primary endpoint was poor renal prognosis, and the patients' prognosis was monitored through follow-up, recording the time at which patients reached the study endpoint. The predictive effect was evaluated using the area under the receiver operating characteristic curve (AUROC), Kaplan-Meier (K-M) curves, and Cox proportional hazards analysis. Compared with the healthy control group, the PLR, NLR, and MLR levels in the LN group were significantly higher (P < 0.05). Kaplan-Meier survival analysis showed that patients with high PLR, NLR, and MLR had poorer prognosis (P < 0.05). Univariate Cox regression analysis indicated that PLR ( 1.002, 95% CI 1.000-1.004, P = 0.05) and NLR ( 1.081, 95% CI 1.031-1.134, P = 0.001) were associated with kidney progression. Multivariate Cox regression analysis showed that only MLR ( 5.861, 95% CI 1.515-22.665, P = 0.010) was an independent risk factor affecting the renal prognosis of LN patients, whereas PLR and NLR were not. Based on the cutoff value of MLR, patients were divided into two groups. In terms of general data, the high MLR group had a significantly higher mean arterial pressure compared to the low MLR group (P = 0.002). In terms of laboratory tests, the high MLR group had a significantly lower eGFR compared to the low MLR group (P = 0.001). In terms of renal pathology, the high MLR group showed statistically significant differences compared to the low MLR group in AI index, CI index, capillary endothelial cell proliferation, cellular/fibrous crescent formation, and interstitial inflammatory cell infiltration (P < 0.05). MLR may serve as an independent risk factor for poor renal prognosis in SLE patients.

The objective of this study is to compare the clinical features and survival outcomes of class IV ± V lupus nephritis (LN) patients, identify risk factors, and develop an accurate prognostic model. This study enrolled patients diagnosed with class IV ± V LN by renal biopsy at Xijing Hospital from December 2013 to June 2023. The composite endpoint of the study was defined as a decline in the estimated glomerular filtration rate (eGFR) by more than 50%, progression to end stage renal disease, or death, whichever came first. The eGFR was calculated utilizing the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. ESRD is defined as an eGFR less than 15ml/min/1.73m , necessitating the commencement of chronic dialysis (hemodialysis or peritoneal dialysis) or kidney transplantation. We compared the baseline features and survival prognosis between patients with class IV ± V LN. The prognostic model was developed using machine learning algorithms and Cox regression. The model's performance was evaluated in terms of discrimination, calibration, and risk classification using the concordance index (C-index), integrated brier score (IBS), net reclassification index (NRI), and integrated discrimination improvement (IDI), respectively. A total of 313 patients were enrolled for this study, including 156 class IV and 157 class IV+V LN. During the median follow-up period of 42.6 (17.0, 83.4) months, 35 (22.4%) class IV and 38 (24.2%) class IV+V LN patients experienced combined events. Class IV and class IV+V patients have similar clinical manifestations, treatment strategies, and long-term prognosis, despite class IV having a higher chronic index (CI) score ( < 0.001). Seven eligible variables (eGFR, CI, age, basophil percentage, red blood cell count, mean arterial blood pressure, and uric acid) were selected to develop the random survival forest (RSF) model. This model demonstrated the best performance with a C-index of 0.771 (0.667, 0.848) and an IBS of 0.144 (0.132, 0.154). The IDI and NRI in the testing set further confirmed that the RSF model exhibited superior risk classification and discrimination capabilities. Class IV ± V LN was similar in clinical manifestations, treatment strategies, and long-term prognosis, despite differences in pathological features. The RSF model we established for class IV ± V LN patients, incorporating seven risk factors, exhibits superior survival prediction and provides more precise prognostic stratification.