Results and prognosis of kidney transplantation in lupus nephritis: Experience of an Argentine center.

INTRODUCTION: Although RT has improved the survival of the population with ESRD due to all causes, renal outcomes in SLE are controversial. The objective of this study is to describe the characteristics and evolution of the patients and the kidney transplant in LN, and compare it with patients transplanted for other causes. MATERIALS AND METHODS: Retrospective, observational, analytical, single-center study in which records of patients undergoing nephrotransplantation for LN were analyzed. They were compared with a group of patients transplanted at the same center for other causes of ESRD. RESULTS: 41 patients with kidney transplant due to SLE and 89 transplanted due to other causes of ESRD were registered. Graft loss occurred in 12 (29.26%) patients with LN and 34 (38.2%) patients in the comparison group (p = .428). Only one case (4.8%) presented reactivation of the LN in the graft, without graft loss. Median graft survival was 73.1 months in the LN group and 66.3 months in the comparison group (p = .221). A total of 8 (19.5%) patients with LN and 11 (12.4%) without LN died (p = .42), with infections being the main cause in both groups. There were no statistically significant differences between groups in graft and patient survival. In a sub-analysis of 28 patients with LN with aPL study, 4 thrombotic events were observed, in 3 different patients, in the aPL-positive group. There were no statistically significant differences in terms of causes of graft loss and graft survival (positive aFL 75.7 months vs negative aFL 72.7 months, p= .96). There were also no differences in mortality between the groups (p = .61). CONCLUSION: Patients transplanted for LN did not differ from the control population in terms of graft and patient survival. Infections were the main cause of death, so prophylaxis and vaccination continue to be a fundamental pillar in the prevention of infections in immunocompromised patients.

Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study.

BACKGROUND: Lupus 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). METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: More 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.

Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis.

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).

Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis.

Systemic lupus erythematosus is a potentially fatal autoimmune disease. Although interleukin-17 (IL-17) has been linked to human lupus and mouse models of this disease, it has not been addressed whether this cytokine plays a critical role in fatal lupus pathology. Here we have demonstrated that increased production of IL-17 cytokines and their signaling via the adaptor protein CIKS (a.k.a. Traf3ip2, Act1) critically contributed to lethal pathology in an FcgammaR2b-deficient mouse model of lupus. Mice lacking IL-17 and especially those lacking CIKS showed greatly improved survival and were largely protected from development of glomerulonephritis. Importantly in this model, potential effects of IL-17 cytokines on antibody production could be distinguished from critical local contributions in kidneys, including recruitment of neutrophils and monocytes. These findings provide the proof of principle that signaling by IL-17 family cytokines mediated via CIKS presents promising therapeutic targets for the treatment of systemic lupus erythematosus, especially in cases with kidney involvement.

Renal function deterioration is an independent mortality determinant in Koreans diagnosed with lupus nephritis.

OBJECTIVE: To evaluate the predictors of mortality, mortality rate, and causes of death in patients with lupus nephritis (LN) depending on final renal function. METHODS: The cohort included 401 Korean patients diagnosed with LN between 1985 and 2019. We retrospectively analyzed the clinical and laboratory indices, treatment response, and the final renal function. The final renal function was defined by the last stable level of eGFR measured in an out-patient department more than 3 times before death occurred and was categorized into five groups depending on CKD stage. RESULTS: The median follow-up time after the diagnosis of LN was 131 months. No difference in baseline demographic characteristics and laboratory findings was found except for the proportion of Hb less than 10 mg/dl and baseline eGFR (p = 0.011 and 0.037). We found no significant differences in therapeutic parameters, but all the response parameters including treatment response at 6 months (p = 0.004) and 12 months (p = 0.004), time to remission (p < 0.001), final renal response (p < 0.001), and the final renal function (p < 0.001) differed significantly between the two groups. In multivariate Cox proportional hazards analysis, the final renal function was an independent risk factor predicting mortality. The main causes of death were infection and SLE flare. Contrary to existing knowledge, SLE flare also triggered mortality in a few patients with LN progressed to end-stage renal disease (ESRD). Only two cases of mortality occurred in the kidney transplantation (KT) group (n = 25) with a median follow-up period of 224 months. The overall mortality rates calculated using the Kaplan-Meier method were 6.8%, 10.3%, 19.7%, and 28.0% at 5, 10, 20, and 30 years, respectively. CONCLUSION: Renal function deterioration was an independent determinant of mortality in Korean patients with LN. SLE flare also caused mortality in patients with LN who required maintenance dialysis, suggesting the benefit of KT on lupus activity and survival.

High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.

OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE). METHODS: Patients 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. RESULTS: SLE 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-ß2-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. CONCLUSIONS: A 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.

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.

Renal deposits of complement factors as predictors of end-stage renal disease and death in patients with lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) increases the risks of end-stage renal disease (ESRD) and death, but these risks are difficult to estimate. Since complement factors play an essential role in the pathogenesis and are deposited in the kidneys as C1q and C3, we studied whether these deposits predict ESRD and death in patients with LN. METHODS: We collected demographic, clinical and pathological data from 183 adult patients with LN classes II-V diagnosed with a first native kidney biopsy. Pathological data included the localization and intensity of immunofluorescence staining of C1q and C3. We obtained dates of incident ESRD and death from the United States Renal Data System and National Death Index, respectively, and evaluated survival curves and hazard ratios for ESRD and death as a composite outcome and as separate outcomes. RESULTS: The presence and intensity of deposits of C1q and C3 in glomeruli, tubular walls and vascular walls differed between classes and were associated with known unfavourable prognostic factors, such as hypertension, hypoalbuminemia and hypocomplementemia. However, over a median follow-up of 7.5 years, their presence and intensity were associated with neither survival free of ESRD and death nor hazard ratios for ESRD and death. CONCLUSION: Renal deposits of complement factors did not predict ESRD and death in patients with LN.

Rituximab use as induction therapy for lupus nephritis: a systematic review.

OBJECTIVE: Rituximab (RTX) has important usage in rheumatoid arthritis and vasculitis. There remains a need for more, better, and safer treatments for patients with lupus nephritis (LN). RTX has been trialed in such patients without definitive conclusions about its effectiveness. As a role for RTX has not been clearly established for LN, we carried out a systematic review and analysis. METHODS: We identified 31 studies of RTX for class I-VI LN, and assessed complete renal response (CRR) and partial renal response (PRR) using criteria including serum creatinine, proteinuria, and urinary sediment. Due to differences in the pediatric presentation of the disease, studies focusing on pediatric patients were excluded. RESULTS: One randomized controlled trial (RCT) showed superiority of RTX+cyclophosphamide (CYC) versus CYC alone (64% vs. 21% CRR and 19% vs. 36% PRR). Six prospective and retrospective studies utilizing RTX monotherapy found 66% CRR or PRR in all patients. Eleven studies that investigated RTX in combination with CYC or mycophenolate mofetil (MMF) also found 66% CRR or PRR in all patients. In total, the CRR for Caucasian, East Asian, and Hispanic patients were 77%, 38%, and 28%, respectively. CONCLUSIONS: RTX appeared to benefit certain LN patients, but most studies were not randomized or properly controlled, were heterogeneous in design, subjects, and LN types, and were not comparable, and must therefore be interpreted cautiously. RTX alone may not deplete B cells sufficiently for the perturbations of LN. In addition, RTX may induce responses differently among patients of different ethnic and racial backgrounds. Furthermore, there were wide variations in the baseline characteristics of the patients, namely LN class, time course of disease, age, and prior immunosuppressive use. We suggest a prospective RCT in patients aged 18-65 years with class IV LN. Ideally, the patients would not have received prior immunosuppression and would better represent different ethnicities. The treatment groups would be RTX, RTX+belimumab, CYC, and MMF groups, with pulse-dose steroids during induction followed by maintenance steroids and MMF. The CRR and PRR would be assessed at 12 and 24 months. This or a similar study might clarify RTX's role in the treatment of LN.

Rubrics for mortality: a real-world observational long-term lupus nephritis cohort.

In this study, we aimed to evaluate long-term patient survival according to demographic data, clinical manifestations of systemic lupus erythematosus (SLE) and previous and current treatments, collected retrospectively. Patient selection required a minimum of four American College of Rheumatology revised criteria for SLE, biopsy-proven lupus nephritis (LN) available for reclassification according to the modified National Institutes of Health proposal for activity and chronicity indices and a minimum follow-up of at least three years since the last renal biopsy. Selection criteria were fulfilled in 25 patients followed for a median of 21 years. Based on the last renal biopsy, an equal number of patients were thus classified as class I/II and IV (n=8) and class III and V (n = 4). The mortality rate for LN was 14%. Having ever been diagnosed with glomerulonephritis (GN) type III or type IV but not class IV alone (p = 0.046), a higher histological chronicity index at the last renal biopsy (p = 0.022), not attaining renal remission one year after induction therapy (p = 0.004), end-stage renal disease on dialysis (p = 0.033) and the extra-renal Systemic Lupus International Collaborating Clinics Damage Index score (p = 0.017) were all significantly associated with mortality. Our results may provide important clues for strict observation protocols in particular categories of LN patients with long-standing disease.

Long-term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil.

INTRODUCTION: Lupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction - CYP or MMF - and the two maintenance therapies - MMF or azathioprine (AZA). METHODS: We retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival. RESULTS: The clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine (p = 0.03). CONCLUSIONS: Long-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.

Transplant outcomes in kidney recipients with lupus nephritis, and systematic review.

BACKGROUND: Despite improved survival of patients with lupus nephritis (LN), some require kidney transplantation because of progression to end-stage renal disease (ESRD). However, the transplant outcomes of these patients and other recipients have not been thoroughly compared. METHODS: In total, 1848 Korean kidney recipients who underwent transplantation from 1998 to 2017 at two tertiary referral centers were evaluated retrospectively. Among them, 28 recipients with LN, and 50 control recipients matched by age, sex, and donor type, were compared with respect to graft and patient survival. We pooled our data with 17 previous cohort studies in which the graft survival of recipients with LN was described in detail. RESULTS: During the median follow-up period of 9.5 years (maximum 21 years), graft failure (GF) occurred in 10.7% and 16.0% of LN and control recipients, respectively. No differences were found in the rates of GF and death-censored graft failure or patient survival between the two groups. The risks of acute T cell-mediated and antibody-mediated rejection were also similar between the two groups. The pooled analysis showed similar 1- and 5-year graft survival rates between LN and control recipients. CONCLUSIONS: Kidney transplantation is an acceptable option in patients with concurrent LN and ESRD.

Long-term predictive value of acute kidney injury classification in diffuse proliferative lupus nephritis with acute kidney injury.

BACKGROUND: The long-term predictive ability of acute kidney injury (AKI) classification based on "Kidney Disease: Improving Global Outcomes"(KDIGO) AKI diagnosis criteria has not been clinically validated in diffuse proliferative lupus nephritis (DPLN) patients with AKI. Our objective was to assess the long-term predictive value of KDIGO AKI classification in DPLN patients with AKI. METHODS: Retrospective cohort study was conducted by reviewing medical records of biopsy-proven DPLN patients with AKI from the First Affiliated Hospital of Wenzhou Medical University between Jan 1, 2000 and Dec 31, 2014. Multivariate Cox regression and survival analysis were performed. RESULTS: One hundred sixty-seven DPLN patients were enrolled,82(49%) patients were normal renal function (No AKI), 40(24%) patients entered AKI-1 stage (AKI-1), 26(16%) patients entered AKI-2 stage (AKI-2) and 19(16%) patients entered AKI-3 stage (AKI-3). The mean follow-up of all patients was 5.1 ± 3.8 years. The patient survival without ESRD of all patients was 86% at 5 years and 79% at 10 years. The patient survival rate without ESRD at 10 yr was 94.5% for No AKI patients, 81.8% for AKI-1 patients, 44.9% for AKI-2 patients and 14.6% for AKI-3 patients. The area under the ROC curve for KDIGO AKI classification to predict the primary end point was 0.83 (95% CI: 0.73-0.93) (P < 0.001). In Cox regression analysis, AKI stage was independently associated with primary endpoint, with an adjusted hazard ratio (HR) of 3.8(95% CI 2.1-6.7, P < 0.001). CONCLUSION: Severity of AKI based on KDIGO AKI category was associated with progression to ESRD in DPLN patients. Analytical data also confirmed the good discriminative power of the KDIGO AKI classification system for predicting long-term prognosis of DPLN patients with AKI.

Systematic review and meta-analysis of clinical outcomes comparison between different initial dialysis modalities in end-stage renal disease patients due to lupus nephritis prior to renal transplantation.

BACKGROUND: Regarding lupus disease activity, morbidity and survival, limited literature concluded conflicting results when comparing hemodialysis versus peritoneal dialysis as initial renal replacement therapies (RRT) prior to transplantation, in lupus nephritis end-stage renal disease (LN-ESRD) patients. This study was aimed to compare the risks of lupus flares, all-cause infections, all-cause cardiovascular events, and mortality, between hemodialysis versus peritoneal dialysis as initial RRT - modality before renal-transplant in LN-ESRD patients, by systematic review and meta-analysis. METHODS: PubMed, EMBASE, and SCOPUS were searched for observational-studies comparing LN-ESRD -patients undergoing hemodialysis (Group1) versus peritoneal-dialysis (Group 2) prior to renal-transplantation, by their risks of lupus flare, all-cause infections, all-cause cardiovascular events, and mortality as outcome measures. Relative-Risks of outcomes between the groups measured overall effects at a 95% significance level. RevMan 5.3 computer software was used for analysis. RESULTS: From search, 16 eligible studies reported 15,636 LN-ESRD -patients prior to renal transplantation with 4616 patients on hemodialysis, 2089 on peritoneal dialysis, 280 directly underwent kidney transplantation, 8319 were eliminated with reasons and 332 participants' details were not reported. Hemodialysis group had higher risk of all-cause cardiovascular events, Relative-Risk = 1.44 (Confidence Interval:1.02, 2.04), p-Value< 0.05. With regards to risks for mortality, flare and all-cause infections, there were trends that were not statistically significant (p-Value> 0.05). CONCLUSION: Except for all-cause cardiovascular events in which peritoneal dialysis is superior to hemodialysis offering better outcomes, both treatment modalities offer more or less similar clinical outcomes as effective initial choices of RRT in LN-ESRD patients prior to renal transplant. THE PROTOCOL REGISTRATION: PROSPERO 2019 CRD42019131600.

Clinicopathologic characteristics and outcomes of lupus nephritis with positive antineutrophil cytoplasmic antibody.

Aims: The aim was to determine whether anti-neutrophil cytoplasmic antibody (ANCA)-positive serology in patients with lupus nephritis (LN) is associated with different clinicopathologic features and outcomes.Methods: In our retrospective analysis, 283 patients were enrolled between 2013 and 2018. Thirty-six patients were ANCA-positive, and this group was compared with the remaining 247 patients who were confirmed as ANCA-negative at the time of biopsy.Results: ANCA-positive LN patients exhibited higher anti-dsDNA antibody titers and serum creatinine levels and lower serum hemoglobin concentrations than ANCA-negative LN patients. On pathological evaluation, segmental endocapillary hypercellularity observed by light microscopy was significantly more common in the ANCA-positive group. This feature was not significantly different in the treatment group, but the response to treatment was significantly different, as was remission (76.1% vs 69.4%, p < 0.001), between the ANCA-negative and ANCA-positive groups. During follow-up, the times to renal replacement therapy (RRT) and death were significantly different between the two unmatched groups (chi-square test, p = 0.041). Multivariate Cox analysis revealed that neurological disorders, ANCA positivity, and the chronicity index (CI) remained independent risk factors for patient survival. Pulmonary infection was the main cause of death and was most often due to fungal infection.Conclusion: ANCA-positive LN patients typically exhibited higher anti-dsDNA antibody titers, lower serum hemoglobin concentrations and worse renal function than ANCA-negative LN patients. Fungal infection was the main cause of death. We observed that ANCA positivity was an independent risk factor for 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%.

Infection-related hospitalization after intensive immunosuppressive therapy among lupus nephritis and ANCA glomerulonephritis patients.

Introduction: This study aimed to investigate the clinical characteristics, risk factors, and outcomes of infection-related hospitalization (IRH) in patients with lupus nephritis (LN) and ANCA glomerulonephritis after intensive immunosuppressive therapy.Methods: Patients diagnosed with LN or ANCA glomerulonephritis who received intensive immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from 2005 to 2014 were enrolled. Demographics, laboratory parameters, immunosuppressive agents, and IRH details were collected. Multivariable Cox regression was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.Results: Totally, 872 patients with 806 LN and 66 ANCA glomerulonephritis were enrolled, and 304 (34.9%) patients with 433 episodes of IRH were recorded. ANCA glomerulonephritis patients were more vulnerable to IRH than LN patients (53.0% vs. 33.4%, p = .001). Multivariable Cox regression analysis showed that ANCA glomerulonephritis (HR = 1.62, 95% CI: 1.06-2.49, p = .027), diabetes (HR = 1.82, 95% CI: 1.03-3.22, p = .039) and a higher initial dose of prednisone (HR = 1.01, 95% CI: 1.00-1.02, p = .013) were associated with a higher likelihood of IRH. Higher albumin (HR = 0.96, 95% CI: 0.94-0.98, p < .001), globulin (HR = 0.98, 95% CI: 0.96-0.99, p = .008), and eGFR (HR = 0.99, 95% CI: 0.99-1.00, p < .001), were associated with a lower likelihood of IRH. The rates of transfer to ICU and mortality for ANCA glomerulonephritis patients were higher than those for LN patients (22.9% vs. 1.9%, p < .001, and 20.0% vs. 0.7%, p < .001, respectively).Conclusions: ANCA glomerulonephritis patients had a higher risk of IRH and poorer outcome once infected after intensive immunosuppressive therapy than LN patients. More strict control for infection risks is required for ANCA glomerulonephritis patients who undergo intensive immunosuppressive therapy.

A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis.

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.

Assessing the relative impact of lupus nephritis on mortality in a population-based systemic lupus erythematosus cohort.

OBJECTIVE: There is limited knowledge on the relative impact of lupus nephritis (LN) on morbidity and mortality in population-based systemic lupus erythematous (SLE) cohorts. Here, the primary aim was to compare mortality rates between patients with and without LN in a population-based SLE cohort. METHODS: The study cohort included all SLE patients resident in the city of Oslo during 1999-2008. Follow-up time was median 14 (0-15) years. Presence of LN was defined according to the 1987 American College of Rheumatology classification criteria for SLE. LN class was determined by renal biopsy. Data on kidney function, including presence of end-stage renal disease (ESRD), were obtained from patient charts. Standardized mortality ratios (SMRs) were estimated by comparing deaths in the SLE cohort with age- and gender-matched population controls. RESULTS: We found that 98/325 SLE patients (30%) developed LN, 92% of whom had occurrence within the first five years from disease onset. Incidence rate of ESRD was 2.3 per 1000 patient-years. A total of 56 deaths occurred during the study period, corresponding to an overall SMR in the SLE cohort of 2.1 (95% confidence interval (CI) 1.2-3.4). Estimated SMR for LN patients was 3.8 (95% CI 2.1-6.2), and for SLE patients without LN it was 1.7 (95% CI 0.9-2.7). CONCLUSION: In this population-based SLE cohort, we found that LN was associated with increased morbidity and mortality, whereas SLE patients who did not develop LN had good overall prognoses regarding survival.

Factors predictive of long-term mortality in lupus nephritis: a multicenter retrospective study of a Japanese cohort.

BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.