Biopsy-proven Lupus Nephritis Research Articles

A Long-Term follow-up Study of Lupus Nephritis in a Single Tertiary Care Centre.

Lupus nephritis (LN) is an immune complex glomerulonephritis, which is a very serious complication of systemic lupus erythematosus (SLE) as it can progress to end-stage kidney disease (ESKD). In this study of 92 renal biopsy-proven LN, the patients were followed up for a minimum period of 2 years with a mean follow-up period of 5.4 ± 3.4 years. The mean serum creatinine of our study population was 1.4 ± 1.53. Our study population included 2 patients with class I lesions, 5 with class II, 22 with Class III, 53 with Class IV, and 10 with Class V lesions. Our therapeutic approach included only oral steroids for class I and class II lesions; for class III, IV, and V lesions, our approach included pulse steroids followed by oral steroids with either intravenous (IV) monthly cyclophosphamide (CYC) or mycophenolate mofetil (MMF). For maintenance, azathioprine or MMF were used along with low-dose oral steroids after 6 months of CYC or MMF. In CYC induction group containing 78 patients (84.7%), 66 patients (84.6%) attained remission (CR + PR), relapse in five patients (6.4%), ESRD on HD in five patients (6.4%), and death in two patients (2.6%). At the end of the study, in all groups, 79 patients (85.86%) were in remission (CR + PR), six patients (6.5%) were in relapse, five patients (5.4%) had reached the ESKD stage on HD, and two patients (2.2%) died.

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.

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

BackgroundThe aim of the study was to investigate the clinical relevance of IgM deposition in patients with lupus nephritis (LN) in a large cohort.Results217 patients with renal biopsy-proven active LN were enrolled. The associations between glomerular IgM deposition and clinicopathological parameters were further analyzed. IgM deposition was positively correlated with glomerular C1q and C3 deposition moderately (r = 0.436, P < 0.001; r = 0.408, P < 0.001, respectively), and inversely correlated with plasma levels of C3 and CFH mildly (r = − 0.138, P = 0.043; r = − 0.147, P = 0.037, respectively). By multivariate analysis, we found that glomerular IgM deposition independently contributed to glomerular C3 deposition in patients with LN (OR = 2.002, 95% CI 1.295–3.094, P = 0.002). In addition, we also found that patients with IgM 0–2+ had similar plasma CFH levels, but in patients with IgM3+–4+, plasma CFH levels were significantly lower (300.4 ± 155.8 μg/mL vs. 429.9 ± 187.5 μg/mL, P < 0.001). Furthermore, patients with high density of glomerular IgM and low levels of CFH had heavier proteinuria, higher serum creatinine and lower plasma C3 levels (5.7 ± 3.1 g/d vs. 4.7 ± 3.5 g/d, P = 0.037; 150.1 ± 121.0 μmol/L vs. 105.6 ± 97.1 μmol/L, P = 0.005; 0.3 ± 0.2 μg/L vs. 0.4 ± 0.2 μg/L, P = 0.04, respectively), comparing with those with low density of glomerular IgM and low levels of CFH.ConclusionsOur results suggested the involvement of glomerular deposited IgM in complement activation and renal injury in LN.

Changing trends in presentation and indications of biopsy in lupus nephritis: data from the Spanish Registry of Glomerulonephritis.

ABSTRACTBackgroundWith the ageing population and changes in the indications of diagnostic and protocol biopsies in systemic lupus erythematosus in recent years, an impact on the incidence and presentation of lupus nephritis (LN) is expected. The aim of this study was to analyse the epidemiological changes regarding clinical and histological presentation of LN in kidney biopsies performed from 1994 to 2019 included in the Spanish Registry of Glomerulonephritis.MethodsWe analysed data from 28 791 kidney biopsies from 130 Spanish hospitals comparing demographic, clinical and histological data. We divided the cohort according to the age of onset of LN into pediatric onset (<18 years), adult onset (18–50 years) and late onset (>50 years).ResultsThe incidence of LN has decreased from 9.6% of all kidney biopsies in the period 1994–2013 to 7% in the last quarter of the observation period (2014–2019) (P < 0.001), despite an increase in the proportion of patients with LN that underwent repeat biopsies (16.6–24%; P < 0.001). The age of onset of LN has increased from 32 ± 14 to 38 ± 14 years (P < 0.001), with an increase in the proportion of late-onset LN (from 13% to 22% of incident LN; P < 0.001). There were no differences in the distribution of histological features at presentation over the study period. Patients with late-onset LN showed fewer gender differences, had lower GFR and presented with less-proliferative forms of LN compared with early-onset LN.ConclusionsThe frequency of biopsy-proven LN has been decreasing in recent years, despite an increasing number of repeat biopsies. Late-onset LN is increasing, presenting with worse kidney function but fewer proliferative lesions compared with younger-onset LN.

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.

Protein Mannosylation as a Diagnostic and Prognostic Biomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic Lupus Erythematosus

Changes in protein glycosylation are a hallmark of immune-mediated diseases. Glycans are master regulators of the inflammatory response being important molecules for the discrimination between "self"/"non-self". We here explored whether lupus nephritis (LN) exhibit an altered cellular glycosylation aiming to identify a unique glycosignature that characterizes LN pathogenesis. A comprehensive tissue glycomics characterization was performed in a cohort of human biopsy-proven LN clinical samples from SLE patients. A combination of advanced tissue mass spectrometry imaging (MSI); in situ glyco-characterization and ex vivo glycophenotyping of human kidney biopsies were performed to structurally map the N-glycans repertoire in LN samples. LN revealed a unique glycan signature characterized by an increased abundance and spatial distribution of unusual mannose-enriched glycans that are typically found in lower microorganisms; this glycosignature was specific of LN as it was not observed in other kidney diseases. Exposure of mannosylated glycans in LN was found to occur at the cell surface of kidney cells promoting an increased recognition by specific glycans-recognizing receptors, expressed by immune cells. This abnormal glyco-signature of LN was demonstrated to be due to a deficient complex N-glycosylation and a proficient O-mannosylation pathway. Moreover, levels of mannosylation detected in kidney biopsies from LN patients at diagnosis were demonstrated to predict the development of chronic kidney disease (CKD) with 93% of specificity. Cellular mannosylation is a marker of LN, predicting the development of CKD, and thus constituting a potential glycobiomarker to be included in the diagnostic and prognostic algorithm of LN.

English

BACKGROUND Lupus nephritis (LN) is very common and significantly affects the prognosis of patients with systemic lupus erythematosus (SLE). Although the diagnosis of LN is obvious sometimes from the simple lab tests, it is important to perform a renal biopsy. We wanted to study the correlation between the clinical, lab parameters and the histopathological grade of LN in a tertiary care centre in South India. METHODS A cross-sectional study was conducted among all patients with biopsy proven LN who underwent a renal biopsy from 19 / 09 / 2017 to 30 / 06 / 2019. Data of 51 patients were obtained. For all the study subjects, a history was obtained, clinical examination was done, and their lab parameters and the renal biopsy report were noted in the proforma. The histology was correlated with the laboratory and clinical data. RESULTS The majority of the patients were females. Maximum patients had class IV LN and class III had more males than any other class of LN. When clinical and laboratory parameters were correlated with histopathological findings, pedal oedema and facial puffiness were found to be correlated with the classes of lupus nephritis with statistical significance. Among investigations, haemoglobin, C3, activity score and 24 -hour urine protein had a statistically significant correlation with the various classes of lupus nephritis. CONCLUSIONS This study suggests some meaningful correlation between pedal oedema, facial puffiness, 24 hours urine protein, haemoglobin levels, C3 levels and activity score with lupus nephritis classes of ISN / RPS 2003 classification. KEY WORDS Lupus, Clinicopathological Correlation

Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study)

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up.Methods/designThis study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test.DiscussionMost patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20–35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients.Trial registrationClinicalTrials.govNCT 02936375. Registered on October 18, 2016.

Treatment Outcomes of Proliferative vs. Non-proliferative Adult Lupus Nephritis: A 10-Year Follow-Up.

IntroductionSystemic lupus erythematosus (SLE) is a systemic disease with clinically heterogeneous outcomes. Lupus nephritis (LN) is a common complication of SLE. LN impacts clinical SLE outcomes both directly, in the form of target organ damage, and indirectly, through the adverse effects of immunosuppressive therapy.Patients & methodsThe study included 402 SLE cases with biopsy-proven lupus nephritis who were under follow-up for the past 13 years at Mansoura Urology and Nephrology Center, Egypt. We studied the differences in outcome among various LN classes and between 275 proliferative cases and 102 non-proliferative cases.ResultsClass IV was the main LN class in our series with renal survival of 60% at 10 years. The major induction regimen after the first biopsy was cyclophosphamide. Mycophenolate mofetil was the main induction and adjunctive regimen after the second biopsy. The mean follow-up period was 6.7 + 5.2 years. Higher serum creatinine, proteinuria, activity, and chronicity indices were noted in proliferative LN. Patients suffering from proliferative lesions received higher immunosuppression and demonstrated higher morbidity than those with non-proliferative lesions. Remission was higher among the non-proliferative compared to the proliferative group.ConclusionsSerum creatinine, proteinuria, and LN class were the most relevant prognostic factors for renal survival among Egyptian LN patients.

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

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

Molecular Signatures of Kidney Antibody–Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy

To characterize kidney and urine antibody secreting cells (ASC) from patients with active lupus nephritis (LN), before and after induction therapy. We included patients with biopsy proven active LN and performed anti-CD138 staining of kidney biopsy samples to visualize ASC. We performed single-cell gene expression profiling on sorted ASC from fresh biopsy samples by multiplex RT-PCR. We used a gene set allowing the study of ASC maturation from plasmablast to long-lived plasma cells. We quantified urine ASC from untreated LN patients at diagnosis and after 6 months of prospective follow up during induction therapy. The number of kidney CD138+ ASC in 46 untreated LN patients correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASC from 3 untreated patients had a plasmablast molecular signature, contrasting with ASC from 4 patients refractory to immunosuppressant drugs that expressed long-lived plasma cells genes and clustered with long-lived bone marrow plasma cells from 2 healthy donors. Some urine ASC with plasmablast signature were detected in patients with untreated active LN. The presence of urine ASC at 6 months was associated with treatment failure. These results suggest a potential interest of ASC-directed therapy in refractory LN.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis.

To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571) Baseline clinical features, serologic markers, and the wGRS were collected The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE Associations among clinical features, wGRS, and the presence of LN were identified. In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p<0.001), had more pleuritis (OR=2.44, p<0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p<0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012) Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

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.

MO215DEPRESSIVE DISORDER IN LUPIC PATIENTS WITH LUPUS NEPHRITIS: DATA FROM A POPULATION OF 67 PATIENTS WITH BIOPSY PROVEN LUPUS NEPHRITIS

Abstract Background and Aims Systemic lupus erythematosus is a multi-organ, multi-systemic autoimmune disease with significant burden on generally young patients. Renal involvement is relatively frequent, recent studies cite a prevalence of 15-60% of patients, and 25% develop end-stage renal disease after 10 years of disease onset. We studied the incidence of depressive disorders in a population of 67 patients with biopsy proven lupus nephritis. Data about depression in patients with renal involvement of lupus is still scarce. We identified variables associated with the development of depressive disorders in lupus patients. Method We concluded a single center transversal study to assess the incidence of depressive disorder in patients with biopsy proven lupus nephritis. We used the self-report Beck Depression/ Anxiety Inventory (BDI/ BAI), 1961/ 1990, translated in Romanian and validated in the Romanian population to diagnose depression. We also wanted to identify risk factors associated with depression in such patients. We used EpiInfo for the statistical analysis and data was extracted from medical records. Results We included in the study patients diagnosed with systemic lupus erythematosus, and had renal biopsy between January 2008 – December 2018. Patients were followe-up until May 2020. Beck Depression/Anxiety Inventory was administered a single time during the follow-up visit between (March 2019 – May 2020). In our study group, 58 patients were female (86.5%). Median age at diagnosis of lupus disease was 29 years (min 10 years, max 62 years). Median duration of the disease until the self-assessment inventory was 10 years (min 1.5 years, max 30 years). Median duration of corticosteroid treatment was 10.1 years (min 1.58 years, max 29). 1 patient had class I, 2 had class II, 12 had class III, 32 had class IV, 12 had class V, 1 had class VI, 1 had classes III+V, 1 had classes IV+V of lupus nephritis (ISN classification of lupus nephritis). 13 patients had normal scores of the Beck Inventory (0-9 points), 7 had mild depression (10 - 15 points), 37 had moderate depression (16- 23 points), 10 had severe depression (24-63 points). We identified female gender (p=0.009), duration of corticosteroid therapy (p=0.036), duration of the lupic disease (p=0.036) to be independently associated with depression development. Other variables, such as creatinine levels at the moment of the assessment, duration of maintenance therapy with mycofenolate mofetil or azathioprine, proteinuria, inflammatory markers were not associated significantly with depression. Conclusion We identified clinical variables associated with depression development in patients with lupus nephritis. The study brings data useful for the clinician, helping doctors focus on the variables that predict depression in lupus patients and making screening for depressive disorders more focused on the patients with risk factors.

POS0690 RANDOMIZED, CONTROLLED, PHASE 2 TRIAL OF TYPE 1 IFN INHIBITOR ANIFROLUMAB IN PATIENTS WITH ACTIVE PROLIFERATIVE LUPUS NEPHRITIS

Background:Anifrolumab, a type I interferon receptor antibody, has shown efficacy in patients with systemic lupus erythematosus (SLE),1,2 &gt;30% of whom develop lupus nephritis (LN).Objectives:To evaluate the efficacy and safety of anifrolumab vs placebo alongside standard therapy in patients with active proliferative LN.Methods:TULIP-LN (NCT02547922) was a phase 2 double-blind trial in adult patients with active, biopsy-proven LN and 24-hour (h) urine protein–creatinine ratio (UPCR) &gt;1 mg/mg. Patients were randomized (1:1:1) to anifrolumab basic regimen (BR, 300 mg, based on SLE dosing1,2), anifrolumab intensified regimen (IR, 900 mg for 3 doses, 300 mg thereafter), or placebo, intravenously every 4 weeks alongside standard therapy of oral glucocorticoids (GCs; mandatory taper ≤10 mg/day by Week [W]12, ≤7.5 mg/day by W24) and mycophenolate mofetil (target 2 g/day by W8). The primary endpoint was the relative difference in change from baseline to W52 in 24-h UPCR, measured with a geometric mean ratio (GMR) of the change in the combined anifrolumab vs placebo groups (GMR &lt;1 favors anifrolumab). The key secondary endpoint was complete renal response (CRR) at W52 (24-h UPCR ≤0.7 mg/mg, estimated glomerular filtration rate ≥60 mL/min/1.73 m2 or no decrease ≥20%, no treatment discontinuation, and no restricted medication use). Sustained GC taper (≤7.5 mg/day, W24–52) was an exploratory endpoint. CRR0.5 (CRR with UPCR ≤0.5 mg/mg) and time to CRR0.5 sustained to W52 were analyzed post hoc. Responder rates were calculated with a stratified Cochran–Mantel–Haenszel approach.Results:Patients received anifrolumab BR (n=45) or IR (n=51) or placebo (n=49); demographics and baseline disease characteristics were generally balanced between groups. No difference in change from baseline to W52 in 24-h UPCR was observed for combined anifrolumab vs placebo groups (Table 1). Anifrolumab clearance was higher in patients with LN vs SLE; proteinuria in LN elicited suboptimal anifrolumab serum concentrations (early trough from BR 50%–60% lower than in SLE trials1,2), so anifrolumab IR results are presented. CRR rate at W52 was numerically higher with the IR vs placebo (45.5% vs 31.1%) (Table 1). Time to sustained CRR0.5 (Figure 1), rate of CRR0.5 at W52, and rate of sustained GC taper to ≤7.5 mg/day (Table 1) were improved with the IR vs placebo. Most adverse events were nonserious, mild, or moderate and did not lead to discontinuation; rates were similar in the combined anifrolumab vs placebo groups (89.8% vs 93.8%). In the combined anifrolumab vs placebo groups, there was a higher incidence of herpes zoster (HZ, 16.7% vs 8.2%); most HZ cases were of mild to moderate intensity, cutaneous, and resolved with treatment.Conclusion:Although the primary endpoint was not met, the anifrolumab IR was associated with numeric improvements across clinical endpoints vs placebo; thus, intensified dosing may be required to reach clinical efficacy in LN vs SLE without active renal disease. Anifrolumab had a similar safety profile in patients with LN and SLE; despite higher frequency of HZ vs placebo, anifrolumab was well tolerated.

Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis.

Whether immunosuppressive therapy may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission. Patients with biopsy-proven LN treated with immunosuppressants (IS) between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24 h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressive therapy, flares according to SLEDAI Flare Index. Predictors of flare were analysed by multivariate logistic regression analysis. Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with IS. Eighty-three patients (34.8%) discontinued IS, 46 (30) months after remission achievement. During a mean (s.d.) follow-up of 116.5 (78) months, 19 patients (22.9%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least 3 years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI: 0.093, 0.867; P = 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95% CI: 0.038, 0.978; P = 0.047), age at IS discontinuation (OR 0.93, 95% CI: 0.868, 0.997; P = 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95% CI: 0.058, 0.920; P = 0.038) were protective against disease flares. Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.

Predictors of Remission in Lupus Nephritis Pati

Background: Lupus nephritis (LN) is a common and serious manifestation of SLE, occurring in more than half of patients with SLE during their course of illness, in 10–25% of such patients, kidney disorder progresses to end-stage renal disease (ESRD). Objective: To determine the predictors of remission in patients with biopsy-proven lupus nephritis, and to assess the long-term renal remission rate in our lupus nephritis patients. Patients and Methods: This is a retrospective observational study carried out at the Rheumatology and Nephrology Units, Internal Medicine Department, Menoufia and Mansoura Universities Hospitals, Egypt for a 1-year duration between 1 June 2019 and 1 June 2020. A total of 60 patients with biopsy-proven LN were studied. Results: In the current study, after six months of follow-up, about two-thirds of patients achieved remission. The urinary protein creatinine ratio (UPCR) of 4.9 g/g, systemic lupus erythematosus disease activity index (SLEDAI) of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. On multivariate analysis, serum creatinine (SCr) at the time of diagnosis is the only independent predictor of remission (complete or partial) at 6 months. According to the receiver operating characteristic curve, the cut-off value of SCr ≤ 2.9 mg/dL with 100% specificity and 98 % sensitivity was a predictor for renal remission. Conclusion:The UPCR of 4.9 g/g, SLEDAI of 20 and Hb of 8.8 g/dl at the third month are valuable for predicting remission at the sixth month in active lupus nephritis. Serum creatinine level ≤2.9 mg/dL at the time of diagnosis was the only independent predictor of complete remission at 6 months.

POS-120 Renal Thrombotic Microangiopathy in Lupus Nephritis: Risk Factors and Clinical Outcomes

Thrombotic microangiopathy (TMA) is a severe disorder associated with poor outcomes. It represents very serious complication of systemic lupus erythematosus (SLE) . The aim of this study was to identify risk factors and clinical outcomes for renal TMA in patients with lupus nephritis (LN) Clinical and renal histopathological data of 50 patients with biopsy-proven LN were retrospectively analyzed in order to compare clinical feature and outcomes in group with and without TMA. 11 patients (22%) were diagnosed with co-existing renal TMA. Five patients (45, 4%) were found to have concomitant APS. the median age of the patient was 27, 4+-9.8. 8 patients (72, 7%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (9 patients, 81, 8%). all patients were treated with glucocorticoids in combination with immunosuppressive agent; no patient was treated with plasma exchange. One patient died due to hemorrhagic shock. Compared to patients without TMA there were no differences in estimated glomerular filtration rate, percentage of patients who required dialysis, renal or patient survival, incidence of chronic kidney disease at last follow-up and rates of treatment failure. TMA was associated with a higher prevalence of hypertension (p=0,030; OR=5,6), pericarditis (p=0,007;OR=11,11), anemia (p=0,024;OR=6,8) AND vasculitis (P=0,005 OR=10,8). Identifying the mechanism underlying the pathogenesis of renal TMA lesions in LN might provide potential targets for the development of novel therapies.

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.

Machine Learning for Prediction and Risk Stratification of Lupus Nephritis Renal Flare

Background: Renal flare of lupus nephritis (LN) is strongly associated with poor kidney outcomes, and predicting renal flare and stratifying its risk are important for clinical decision-making and individualized management to reduce LN flare. Methods: We randomly divided 1,694 patients with biopsy-proven LN, who had achieved remission after treatment, into a derivation cohort (n = 1,186) and an internal validation cohort (n = 508), at a ratio of 7:3. The risk of renal flare 5 years after remission was predicted using an eXtreme Gradient Boosting (XGBoost) method model, developed from 59 variables, including demographic, clinical, immunological, pathological, and therapeutic characteristics. A simplified risk score prediction model (SRSPM) was developed from important variables selected by XGBoost model using stepwise Cox regression for practical convenience. Results: The 5-year relapse rates were 39.5% and 38.2% in the derivation and internal validation cohorts, respectively. Both the XGBoost model and the SRSPM had good predictive performance, with a C-index of 0.819 (95% confidence interval [CI]: 0.774–0.857) and 0.746 (95% CI: 0.697–0.795), respectively, in the validation cohort. The SRSPM comprised 6 variables, including partial remission and endocapillary hypercellularity at baseline, age, serum Alb, anti-dsDNA, and serum complement C3 at the point of remission. Using Kaplan-Meier analysis, the SRSPM identified significant risk stratification for renal flares (p < 0.001). Conclusions: Renal flare of LN can be readily predicted using the XGBoost model and the SRSPM, and the SRSPM can also stratify flare risk. Both models are useful for clinical decision-making and individualized management in LN.