Biopsy-proven Lupus Nephritis Patients Research Articles

Nomogram for predicting proliferative lupus nephritis in patients with low-level proteinuria.

Proliferative lupus nephritis (LN) is not uncommon in individuals with proteinuria < 0.5 g/24h, highlighting the importance of predicting proliferative nephritis for effective clinical management. We aimed to develop a predictive model for proliferative nephritis in this population. The enrolled 671 biopsy-proven LN patients were divided into low-level proteinuria (< 0.5 g/24 h) and high-level proteinuria (≥ 0.5 g/24 h) groups. The clinical features, pathological characteristics and long-term outcomes of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to construct a predictive nomogram for proliferative nephritis in low-level proteinuria patients and internal validation was performed using bootstrap-resampling. 103 of 671 (15.4%) LN patients had low-level proteinuria, while 43 (41.7%) of whom showed proliferative LN, and the activity index and chronicity index were 5 (IQR [4,7]) and 3 (IQR [2,4]), respectively. The long-term adverse renal events-free survival was preferable in the low-level proteinuria group. The LASSO-logistic regression identified that age, sex, mean arterial pressure, haemoglobin, platelet, 24-h proteinuria and anti-double strands DNA antibodies positivity were associated with proliferative nephritis in those with low-level proteinuria. The predictive model showed an area under curve of 0.900 (95% CI: 0.840-0.960) and a bootstrapped result of 0.894 (95% CI: 0.832-0.965), with good calibration. 41.7% of the patients with low-level proteinuria exhibited proliferative LN when biopsied. The nomogram including clinical, urinary, and laboratory parameters might help with the prediction of proliferative LN before biopsy among patients with low-level proteinuria.

Serum antineutrophil cytoplasmic antibody positivity at the time of renal biopsy is associated with disease activity of lupus nephritis

Objective To investigate the correlations between serum antineutrophil cytoplasmic antibody (ANCA) and clinicopathological features, induction treatment response, and prognosis of lupus nephritis (LN) patients. Methods In this retrospective study, biopsy-proven LN patients from October 2010 to September 2020 were tested for serum ANCA by indirect immunofluorescence and ELISA and were divided into ANCA-positive group and ANCA-negative group. The clinicopathological data of the two groups were analyzed and compared. Results Thirty-five of 115 patients (30.43%) were seropositive for ANCA. ANCA-positive patients had significantly higher systemic lupus erythematosus activity index and activity index scores, higher 24-h urinary protein, and lower complement three levels (p = 0.001, 0.028, 0.023, 0.009, respectively). The incidences of oral ulcers, thrombocytopenia, and leukocyturia, and the positive rates of anti-dsDNA antibody and anti-histone antibody were significantly higher in ANCA-positive group (p = 0.006, 0.019, 0.012, 0.001, 0.019, respectively). Class IV LN and fibrinoid necrosis/karyorrhexis were significantly more common in the ANCA-positive group (p = 0.027, 0.002). There was no significant difference in the total remission rate of ANCA-positive patients receiving cyclophosphamide and mycophenolate mofetil as induction therapies (83.33% vs. 66.67%, p > 0.05), while patients receiving cyclophosphamide as induction therapy had a higher total remission rate than those receiving other immunosuppressants (83.33% vs. 20%, p = 0.028). Conclusions LN patients with ANCA seropositivity at renal biopsy have a significantly higher disease activity, and their pathological manifestations are predominantly proliferative LN. These patients require a more active immunosuppressive therapy with cyclophosphamide or mycophenolate mofetil to improve their remission rate.

Interstitial fibrosis increases the risk of end-stage kidney disease in patients with lupus nephritis.

To evaluate the risk of end-stage kidney disease (ESKD) in LN patients using tubulointerstitial lesion scores. Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions [e.g. interstitial inflammation (II), tubular atrophy (TA) and interstitial fibrosis (IF)] were analysed. The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n = 3, 2%), class III/IV (n = 119, 78.8%), class V (n = 23, 15.2%) and class VI (n = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, nine (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine [hazard ratio (HR): 1.7, 95% CI: 1.42-2.03, P < 0.001] and IF (HR: 3.2, 95% CI: 1.58-6.49, P = 0.001) as independent risk factors of ESKD. Kaplan-Meier analysis further confirmed a heightened risk of ESKD associated with IF. Tubulointerstitial involvement is commonly observed in the histopathological presentation of LN. However, IF, rather than II or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, the degree of IF should be reviewed.

Urine Proteomics Link Complement Activation with Interstitial Fibrosis/Tubular Atrophy in Lupus Nephritis Patients

BackgroundIntrarenal complement activation has been implicated in the pathogenesis of tubulointerstitial fibrosis in lupus nephritis (LN) based on prior animal studies. The assembly of the membrane attack complex (MAC) by complement C5b to C9 on the cell membrane leads to cytotoxic pores and cell lysis, while CD59 inhibits MAC formation by preventing C9 from joining the complex. We hypothesize that complement activation and imbalance between complement activation and inhibition, as defined by increased production of individual complement components and uncontrolled MAC activation relative to CD59 inhibition, are associated with interstitial fibrosis and tubular atrophy (IFTA) in LN and correlate with the key mediators of kidney fibrosis- transforming growth factor receptors beta (TGFRβ), platelet-derived growth factor beta (PDGFβ) and platelet-derived growth factor receptor beta (PDGFRβ). MethodsWe included urine samples from 46 adults and pediatric biopsy-proven lupus nephritis patients who underwent clinically indicated kidney biopsies between 2010 and 2019. We compared individual urinary complement components and the urinary C9-to-CD59 ratio between LN patients with moderate/severe IFTA and none/mild IFTA. IFTA was defined as none/mild (<25% of interstitium affected) versus moderate/severe (≥ 25% of interstitium affected). Proteomics analysis was performed using mass spectrometry (Orbitrap Fusion Lumos, Thermo Scientific) and processed by the Proteome Discoverer. Urinary complement proteins enriched in LN patients with moderate/severe IFTA were correlated with serum creatinine, TGFβR1, TGFβR2, PDGFβ, and PDGFRβ. ResultsOf the 46 LN patients included in the study, 41 (89.1%) were women, 20 (43.5%) self-identified as Hispanic or Latino, and 26 (56.5%) self-identified as Black or African American. Ten of the 46 (21.7%) LN patients had moderate/severe IFTA on kidney biopsy. LN patients with moderate/severe IFTA had an increased urinary C9-to-CD59 ratio [median 0.91 (0.83-1.05) vs 0.81 (0.76-0.91), p=0.01]. Urinary C3 and CFI levels in LN patients with moderate/severe IFTA were higher compared to those with none/mild IFTA [C3 median (IQR) 24.4(23.5-25.5) vs. 20.2 (18.5–22.2), p= 0.02], [CFI medium (IQR) 28.8 (21.8-30.6) vs. 20.4 (18.5-22.9), p=0.01]. Complement C9, CD59, C3 and CFI correlated with TGFβR1, PDGFβ, and PDGFRβ, while C9, CD59 and C3 correlated with TGFβR2. ConclusionThis study is one of the first to compare the urinary complement profile in LN patients with moderate/severe IFTA and none/mild IFTA in human tissues. This study identified C3, CFI, and C9-to-CD59 ratio as potential markers of tubulointerstitial fibrosis in LN.

The Association of Urinary MCP-1 with Disease Activity of Lupus Nephritis

Background: The association of urinary MCP-1 (Monocyte Chemoattractant Protein-1) with disease activity in lupus nephritis (LN) has been a subject of significant interest. MCP-1 is a chemokine involved in the recruitment and activation of monocytes, which play a critical role in the pathogenesis of LN. Objective: To assess association of Urinary MCP-1 with disease activity of lupus nephritis. Method: This cross sectional study was conducted in the Department of Nephrology, Dhaka Medical College Hospital, Dhaka from January, 2017 to June, 2018. This cross sectional study was performed on 60 biopsy proven lupus nephritis patients and 30 age and sex matched apparently healthy control subjects. All the patients were recruited as per inclusion and exclusion criteria. Diagnosed SLE patients who had renal involvement and undergone renal biopsy for standard clinical indications were recruited by purposive sampling and divided into two groups of active and inactive LN as per operational definition. Results: During the study, The urinary MCP-1 was higher in active LN patients compared to the inactive group and both were higher than the level in the control. Plus, highest Sensitivity and specificity of uMCP-1 observed at cutoff value 433 pg/ml, where sensitivity was 0.967 and specificity was 0.900. Among 30 active lupus nephritis cases raised uMCP-1 was found in 29 cases and among 30 inactive lupus nephritis cases raised uMCP-1 was found in 3 cases. uMCP-1 showed very good agreement in diagnosis of lupus nephritis activity according to Kappa statistics. uMCP-1 in diagnosis of lupus nephritis activity showed accuracy, sensitivity, specificity, PPV and NPV were 0.933, 0.967, 0.900, 0.906 and 0.964 respectively. Conclusion: In conclusion, urinary MCP-1 holds great promise as a useful biomarker for the determination of lupus nephritis activity. Its association with disease activity, predictive value for treatment response and renal outcomes, and non-invasive nature make it an ...

A Study on Clinical and Laboratory Status of Active and Inactive LN Patients

Background: Lupus nephritis (LN) is a significant manifestation of systemic lupus erythematosus (SLE) that affects the kidneys. Differentiating between active and inactive LN is essential for determining disease activity, tailoring treatment strategies, and monitoring patient outcomes. The clinical and laboratory status of LN patients provides valuable insights into the severity of renal involvement, response to treatment, and the potential for disease progression. Objective: To asses clinical and laboratory status of active and inactive LN patients. Method: This cross sectional study was conducted in the Department of Nephrology, Dhaka Medical College Hospital, Dhaka from January, 2017 to June, 2018. This cross sectional study was performed on 60 biopsy proven lupus nephritis patients and 30 age and sex matched apparently healthy control subjects. All the patients were recruited as per inclusion and exclusion criteria. Diagnosed SLE patients who had renal involvement and undergone renal biopsy for standard clinical indications were recruited by purposive sampling and divided into two groups of active and inactive LN as per operational definition. Results: During the study, Mean age of the lupus nephritis patients in active and inactive LN was 26.60 ± 8.36 years and 28.80 ± 9.18 years respectively. Most of the patients in both groups were female. Anaemia and edema was observed significantly higher in active than that of inactive lupus nephritis. Systolic and diastolic blood pressure was significantly higher in active lupus nephritis than that of inactive lupus nephritis patients. Hb, serum C3 and eGFR were significantly lower in active LN than that of inactive LN. RBC, WBC, platelet count were also lower in active LN than that of inactive LN but no significant difference was observed between two groups. ESR, serum creatinine, proteinuria, Anti ds DNA Ab titre and uMCP-1 were significantly higher in active LN than that of inactive LN. There was no difference between active and inactive LN patients with regards the use of medications. There was no difference in renal biopsy classes in between two groups. Conclusion: According to our study findings, active lupus nephritis (LN) patients exhibited elevated systolic and diastolic blood pressure compared to those with inactive LN. Additionally, active LN patients displayed lower levels of hemoglobin, serum C3, and estimated glomerular filtration rate (eGFR) compared to inactive LN patients. While red blood cell (RBC), white blood cell (WBC), and platelet counts were also lower in active LN patients, the difference between the two groups did not reach statistical significance. Furthermore, there were no notable differences in medication usage between active and inactive LN patients, and the distribution of renal biopsy classes was similar in both groups.

Clinicopathological characteristics and outcomes of lupus nephritis patients with scanty immune depositions in kidneybiopsies.

The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear. Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models. Among 498 lupus nephritis patients, 81 were diagnosed withscanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferativefeatures at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significantrisk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients. Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients.

Disease modification achievement in patients with lupus nephritis in a real-life setting: mission impossible?

ObjectiveA preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify...

Association between glomerular mTORC1 activation and crescents formation in lupus nephritis patients.

This study aims to explore the association between glomerular mammalian target of rapamycin complex 1 (mTORC1) pathway activation and crescents' degree in lupus nephritis (LN) patients. A total of 159 biopsy-proven LN patients were enrolled in this retrospective study. The clinical and pathological data of them were collected at the time of renal biopsy. mTORC1 pathway activation was measured by immunohistochemistry, expressed by the mean optical density (MOD) of p-RPS6 (ser235/236), and multiplexed immunofluorescence. The association of mTORC1 pathway activation with clinico-pathological features especially renal crescentic lesions, and the composite outcomes in LN patients was further analyzed. mTORC1 pathway activation could be detected in the crescentic lesions and was positively correlated with the percentage of crescents (r=0.479, P<0.001) in LN patients. Subgroup analysis showed mTORC1 pathway was more activated in patients with cellular or fibrocellular crescentic lesions (P<0.001), but not fibrous crescentic lesions (P=0.270). The optimal cutoff value of the MOD of p-RPS6 (ser235/236) was 0.0111299 for predicting the presence of cellular-fibrocellular crescents in >7.39% of the glomeruli by the receiver operating characteristic curve. Cox regression survival analysis showed that mTORC1 pathway activation was an independent risk factor for the worse outcome (defined by composite endpoints of death, end-stage renal disease and a decrease of >30% in eGFR from baseline). Activation of mTORC1 pathway was closely associated with the cellular-fibrocellular crescentic lesions and could be a prognostic marker in LN patients.

WCN23-0887 Prevalence and Clinical Significance of Anti Phospholipid Antibodies in Biopsy Proven Lupus Nephritis Patients in a suburban tertiary care center - An Interim Analysis

WCN23-0887 Prevalence and Clinical Significance of Anti Phospholipid Antibodies in Biopsy Proven Lupus Nephritis Patients in a suburban tertiary care center - An Interim Analysis

Peripheral Eosinophil Count Associated with Disease Activity and Clinical Outcomes in Hospitalized Patients with Lupus Nephritis

Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients. Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months. Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015–0.057) ×10⁹/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90–0.97; and OR 0.96, 95% CI: 0.93–0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 10⁹/L. Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN.

Potential role of circulating miRNA-146a and serum kallikrein 1 as biomarkers of renal disease in biopsy-proven lupus nephritis patients

Aim of the workTo evaluate the performance of circulating miR-146a and serum kallikrein1 (KLK1) as biomarkers for detecting disease activity and distinguishing histopathological changes associated with lupus nephritis (LN). Patients and methods90 systemic lupus erythematosus (SLE) patients (44 with active non-renal disease and 46 with LN) were examined for relative expression levels of circulating miR-146a, assessed by reverse transcription quantitative real-time PCR (RT-qPCR) and serum KLK1 levels, measured by ELISA. SLE disease activity was assessed using SLEDAI-2 k. Receiver operating characteristic curve was employed to examine the diagnostic performance of both biomarkers and established conventional laboratory parameters of renal function with specific renal histologic features seen in LN. As well, 40 apparently healthy control subjects were enrolled. ResultsCirculating miR-146a levels were significantly lower (p < 0.01), while serum KLK1 levels were significantly higher (p < 0.01) in active LN patients compared to active non-renal and controls. miR-146a levels negatively correlated with serum creatinine, Albumin/Creatinine and SLEDAI-2 k (p ≤ 0.01), while serum KLK1 significantly correlated with serum creatinine, Albumin/Creatinine and C3 (p ≤ 0.05) and inversely with miR-146a (p = 0.002). Both circulating miR-146a and KLK1 revealed an outstanding performance in predicting renal activity among SLE patients with an AUC of 0.949 and 0.947 respectively. In active LN patients, KLK1 and miR-146a exhibited good ability in differentiating proliferative from non-proliferative LN (AUC 0.73, 0.65 respectively), and in predicting biopsy activity index ≥7, surpassing conventional disease measures. ConclusionCirculating miR-146a and serum KLK1 are potential biomarkers for LN that could compete with invasive renal biopsy. Independent validation is warranted.

Variations in clinical presentation and biomarkers among biopsy-proven lupus nephritis patients: a Top End retrospective cohort study.

Lupus nephritis (LN) is a common feature of systemic lupus erythematosus (SLE) and affects 50% of patients with SLE. Racial differences in incidence and prevalence have been well documented worldwide. In Australia, higher incidence and prevalence of SLE had been previously reported in Aboriginal and Torres Strait Australians compared with non-Indigenous Australians. To describe the differences in clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australian and non-Indigenous Australian patients with LN. We retrospectively identified all consecutive biopsy-proven LN patients in our institution and compared the clinical features and lupus biomarkers between Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians. Of the 33 consecutive biopsy-proven LN patients, 26 self-identified as of Aboriginal and Torres Strait Islander descent. The estimated incidence of LN in Aboriginal and Torres Strait Islander Australian and non-Indigenous Australians were 5.08 and 0.47 per 100 000 patient-years respectively. Neurological manifestations (23.08% vs 0%), haematological manifestations (46.50% vs 16.67) and right-heart catheter proven pulmonary arterial hypertension (23.08% vs 0%) were more frequently observed among Indigenous Australian patients compared with non-Indigenous Australian patients. The incidence of positive extractable nuclear antigen was also higher among Indigenous Australian patients (84.62% vs 57.14%). The present study further supports the observation that lupus in Aboriginal and Torres Strait Islander Australians were of a 'distinct phenotype' compared with non-Indigenous Australians. Future research should be aimed at delineating the reason for this observed difference.

Novel loss-of-function mutations in TNFAIP3 gene in patients with lupus nephritis.

Heterozygous loss-of-function mutations in the tumour necrosis factor alpha induced protein 3 (TNFAIP3) gene cause an early-onset auto-inflammatory disease named haploinsufficiency of A20 (HA20). Here we describe three unrelated patients with autoimmune lupus nephritis (LN) phenotypes carrying three novel mutations in the TNFAIP3 gene. Whole-exome sequencing (WES) was used to identify the causative mutations in three biopsy-proven LN patients. Sanger sequencing and quantitative polymerase chain reaction (qPCR) were used to validate the mutations identified by WES. RNA sequencing, qPCR and cytometric bead array was used to detect inflammatory signatures in the patients. The patients predominantly presented with an autoimmune phenotype, including autoimmune haemolytic anaemia, multipositive autoantibodies and LN. Additionally, novel phenotypes of allergy and pericardial effusion were first reported. WES identified three novel heterozygous mutations in the TNFAIP3 gene, including a novel splicing mutation located in the canonical splicing site (c.634+2T>C)resulting in an intron 4 insertion containing a premature stop codon, a de novo novel copy number variation (exon 7-8 deletion) and a novel nonsense mutation c.1300_1301delinsTA causing a premature stop codon. We further identified hyperactivation signatures of nuclear factor- kappa B and type I IFN signalling and overproduction of pro-inflammatory cytokines in the blood. This report expanded the phenotype to a later age, as two girls were diagnosed at age 3 years and one man at age 29 years. Kidney involvement may be the main feature of the clinical spectrum of HA20, even in adults. Genetic screening should be considered for early-onset LN patients.

Ki-67 proliferative index in kidney biopsies of lupus nephritis patients: a preliminary study

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that involves multiple organs including the kidneys, skin, joints and serous membranes. Previous studies have shown that elevated Ki-67 indices are correlated with the cellular proliferation and clinical findings in lupus nephritis (LN). Objectives: The aim of this study was to examine the relationship between glomerular, tubular and interstitial expression of Ki-67 in kidney biopsy specimens of different classes of LN and and various clinicopathological features. Patients and Methods: This cross-sectional study was conducted on 16 biopsy-proven LN patients. The diagnosis of LN was based on renal biopsy findings, particularly by immunofluorescence (IF) study. The diagnosis of LN with IF was concluded by the deposition of C1q in association with prominent IgG and C3 deposits and the deposition of IgM and IgA (full-house pattern). The morphologic variables on light microscopy were also examined. In this study, the glomerular (gKi-67), interstitial (iKi-67) and tubular (tKi-67) expressions of Ki-67 were assessed. Results: This study comprised of 16 cases of biopsy-proven LN which were stained for Ki-67 with immunohistochemistry. Of the 16 patients, 13 (81.2%) were females. The mean ± SD of age, quantity of proteinuria and serum creatinine in all patients were 37±11.6 years, 1844±582 mg/d and 1.5±0.93 mg/ dL, respectively. Our study showed that the association between gKi-67, iKi-67, and tKi-67 with age, gender, level of proteinuria and serum creatinine was not significant (P&gt;0.05). The association between Ki-67 with interstitial fibrosis, the number of crescents, and the activity and chronicity percentages was also not significant (P&gt;0.05). Moreover, the relationship of gKi-67 with global versus segmental involvement of the glomeruli was not significant (P&gt;0.05). Furthermore, the correlation of gKi-67 with IgA, IgG, IgM, C3 and C1q deposits was not significant (P&gt;0.05). The association of iKi-67 with age, gender, level of proteinuria and serum creatinine was not significant as well. However, the correlation of iKi-67 with C1q deposits was inversely significant (r=-0.544, P=0.029); however this correlation was not significant with IgA, IgG, IgM and C3 deposits (P&gt;0.05). Conclusion: In this study, the relationship of iKi-67 with C1q deposits suggests that C1q has a significant role in the inflammatory process of LN. Since our study was conducted on a relatively small sample size, it, therefore, requires further investigations on larger samples.

Anti-DFS70 Antibodies Are Associated With Proliferative Lupus Nephritis and Renal Pathological Activity.

ObjectiveThe significance of anti-dense fine speckles 70 (DFS70) antibodies in systemic lupus erythematosus (SLE) is still unclear, especially in lupus nephritis (LN) patients. We investigated the prevalence, clinical and pathological relevance of anti-DFS70 antibodies in LN patients.MethodsAnti-DFS70 antibodies were measured using enzyme-linked immunosorbent assays in 377 biopsy-proven LN patients, 268 non-LN SLE patients, 232 chronic kidney disease (CKD) patients, and 78 healthy individuals (HI). Demographic, clinical, and pathological parameters were compared between LN patients with and without anti-DFS70 antibodies. Stepwise multivariable logistic regression was performed to identify covariates associated with anti-DFS70 antibodies.ResultsThe prevalence of anti-DFS70 antibodies in LN (19.6%) was comparable to non-LN SLE patients (19.8%, P=0.9630), but was significantly higher than CKD patients (13.4%, P=0.0468) and HI (9.0%, P=0.0252). Using multivariable logistic regression analysis, the titer of anti-double-stranded DNA (dsDNA) antibodies (adjusted odds ratio=1.002, 95% confidence interval 1.001-1.003, P=0.004) was associated with positive anti-DFS70 antibodies in LN patients. In addition, anti-DFS70 antibodies were more prevalent in proliferative LN (22.0%, 68/309) compared to membrane LN patients (10.2%, 6/59, P=0.0376). Furthermore, LN patients with positive anti-DFS70 antibodies had significantly higher activity index (AI) compared to patients who were negative (8.0 vs 6.0, P=0.0131). However, the chronicity index was similar between the groups (3.0 vs 3.0, P=0.8412).ConclusionAnti-DFS70 antibodies were not associated with LN development in SLE patients but were associated with anti-dsDNA antibodies, proliferative LN, and renal AI. This suggests their potential to serve as a non-histological biomarker for LN subclass and activity status.

Allogeneic adipose-derived mesenchymal stromal cell transplantation for refractory lupus nephritis: Results of a phase I clinical trial

BackgroundMesenchymal stromal/stem cells (MSCs) are known for their immunomodulatory properties. This study was performed to analyse the effects of MSC transplantation on treatment-resistant lupus nephritis (LN). MethodsIn this phase I trial, nine biopsy-proven LN patients refractory to standard treatments underwent systemic infusion of 2 × 106 allogeneic adipose-derived (AD) MSCs/kg and were followed for 12 months post-intervention. ResultsThe treatment protocol resulted in no major adverse events. Urine protein levels significantly decreased during the first month post-intervention (baseline vs. month 1 (median): 1800 vs. 1020, P = 0.008), followed by a gradual increase but remained significantly lower than baseline only up to the 3rd month. During the first 3 months post-intervention, complete renal response (proteinuria < 0.5 g/24 h) and partial response (proteinuria > 0.5 g/24 h, but > 50% decrease in proteinuria) were observed in 33.3% and 44.4% of the patients, respectively, though these rates declined thereafter. Median score of Systemic Lupus Erythematosus Disease Activity Index decreased significantly from 16 at the baseline to 6 at sixth months post-treatment (P = 0.007), though it slightly increased at the 12th month follow-up. ConclusionsAllogenic AD-MSC transplantation was associated with favourable safety and efficient to reduce urine protein excretion and disease activity; however, the maximum effect (greatest improvement in outcomes) was observed at 1 month based on the proteinuria, and 6 months post-intervention based on disease activity scores. A single dose of AD-MSCs may not be adequate to maintain long-term remission of refractory LN, and so, additional doses may be required.

A study on the relationship between morphological lesions of lupus nephritis with demographic and biochemical findings

Introduction: Lupus nephritis is one of the important aspects of systemic lupus erythematosus (SLE). Objectives: This study aimed to investigate possible relationship between pathological lesions of lupus nephritis classes and demographic and biochemical findings among patients. Patients and Methods: This is a cross-sectional study that was conducted on a group of renal biopsy proven lupus nephritis patients using lupus nephritis classification of ISN/RPS 2003. We collected demographic data of all patients including age, gender serum creatinine and 24h proteinuria. Results: Data of 101 patients, of whom 78 (77.23%) were females and mean age of 33.54±13.15 years. The mean serum creatinine and proteinuria were 1.54±0.88 mg/dL 2502.5±1495.05 mg/d. Based on our data, IV-G (class IV, diffuse lupus nephritis-global) lupus nephritis class was the most common (39.6%) followed by class III (23.8%). The mean crescent and sclerotic glomeruli were 1.66±3.32 and 2.27±5.32, respectively. In this study, 24 hours proteinuria, serum creatinine, activity percent, chronicity percent, crescent and glomerular sclerosis between genders showed no significant differences (P&gt;0.05). The correlation between plasma creatinine and activity was directly positive and significant (r=0.381, P=0.001). In addition, a significant correlation between C1q deposits and glomerular sclerosis (P=0.031) was detected. Accordingly, a significant correlation between IgG deposits and lupus nephritis classification (P=0.025) was seen. Conclusion: Lupus nephritis of IV-G and III classes of lupus nephritis were most common among patients and higher IgG deposits were observed in patients with IV-G classification. We found a significant correlation between glomerular sclerosis and C1q deposits that could be an indicator of lupus nephritis activity and severity. However, we recommend further studies in this regard.

The Spectrum of C4d Deposition in Renal Biopsies of Lupus Nephritis Patients.

ObjectivesThis study aimed to determine the prevalence and localization of complement factor C4d in renal biopsies from patients with lupus nephritis (LN), as well as its associations with the disease’s clinico-pathological features. The correlation between arteriolar C4d deposition and renal microvascular lesions (RVLs) was further analyzed.MethodsA total of 325 biopsy-proven LN patients were enrolled, and their clinico-pathological data were collected. C4d staining of renal biopsies was performed by immunohistochemistry. The associations between C4d deposition and the clinico-pathological features were further analyzed.ResultsC4d deposition was present in most (98.8%) renal specimens in our cohort. These deposits were localized in the glomeruli (98.2%), tubular basement membrane (TBM) (43.7%), arterioles (31.4%), and peritubular capillary (33.8%). Patients with TBM C4d staining had higher disease activity (measured with the Systemic Lupus Erythematous Disease Activity Index) and higher National Institutes of Health pathological activity and chronicity indices (all P < 0.01). Patients with arteriolar C4d deposition were more likely to develop RVLs (91.2%) compared to those with no arteriolar C4d deposition (78.0%; P = 0.004), especially with two or more types of RVLs (P < 0.001). During the mean follow-up of 55.8 months, arteriolar C4d was related to worse renal outcomes [hazard ration (HR): 2.074, 95% confidence interval (CI) 1.056–4.075, P = 0.034]. Multivariate Cox hazard analysis showed that co-deposition of arteriolar C4d and C3c was an independent risk factor (HR: 3.681, 95% CI 1.519–8.921, P = 0.004) for predicting renal outcomes.ConclusionsC4d deposition was common in renal tissues from LN patients. TBM C4d deposition was related to the disease activity, and arteriolar C4d deposition was associated with RVLs and worse renal outcomes.

Predictors of renal flares and long-term renal outcome in patients with lupus nephritis: results from daily clinical practice.

To describe renal outcomes of the lupus nephritis (LN) population of the University Medical Centre Groningen (UMCG) in the Netherlands and to identify predictors for renal flares and long-term renal outcome in daily clinical practice. A retrospective analysis of biopsy-proven LN patients with induction and maintenance treatment in the UMCG between 1982 and 2016 was performed. Data were collected at time of diagnosis, after 6 months and every year up to 10 years after diagnosis. Outcome measures were renal relapse (biopsy proven), progression to chronic kidney disease (CKD) stage 3 or 4 and chronic renal replacement therapy. The ability of serum creatinine, proteinuria, creatinine clearance, serum anti-double stranded DNA (anti-dsDNA) antibodies, serum complement 3 (C3) and serum complement 4 (C4), as well as biographic data and histopathological class to predict long-term renal outcome was assessed. Seventy-one patients were included, with median follow-up of 120 months (IQR 48-120 months). During follow-up - up to 10 years - twenty-one (30%) patients experienced at least one relapse. Eleven (15%) patients had CKD stage 3 or 4, of whom eight showed persistent CKD since baseline and two (3%) patients required chronic renal replacement therapy. At baseline, low levels of serum C3 were a significant predictor of renal relapse. Low levels of C3 and C4 at 6 and 12 and proteinuria and high levels of anti-dsDNA at 12 months were significant predictors of renal relapse. At baseline, 6 months and 12 months serum creatinine and creatinine clearance were significant predictors for persistent or newly developed CKD 3 or 4, and need for chronic renal replacement therapy. Almost one-third of LN patients experience at least one renal relapse during long-term follow up, but only 3% need chronic renal replacement therapy. Our data suggests that early serological remission is associated with a low risk of renal relapse. Decreased renal function at onset and the first year after diagnosis is predictive for decreased renal function at a later stage.