The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 2021

2021 ◽  
Author(s):  
Hans-Joachim Anders ◽  
Jerome Loutan ◽  
Annette Bruchfeld ◽  
Gema Maria Fernandez Juarez ◽  
Jürgen Floege ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Class Iii ◽  
Class V ◽  
Alternative Drug ◽  
Biopsy Interpretation ◽  
Diagnostic Work ◽  
Work Up ◽  
Active Class ◽  
Therapy Treatment

Abstract In 2019 and 2021, the European League for Rheumatism (EULAR) jointly with the European Renal Association (ERA) and the Kidney Disease Improving Global Outcomes (KDIGO), respectively, released updated guidelines on the management of lupus nephritis. The Immunology Working Group of the ERA reviewed and compared both updates. Recommendations were either consistent or differences were of negligible clinical relevance for: Indication for kidney biopsy, kidney biopsy interpretation, treatment targets, hydroxychloroquine dosing, first line initial immunosuppressive therapy for active class III, IV (±V) LN, pregnancy in LN, LN in paediatric patients, and LN patients with kidney failure. Relevant differences in the recommended management relate to the recognition of lupus podocytopathies, uncertainties in steroid dosing, drug preferences in specific populations and maintenance therapy, treatment of pure class V LN, therapy of recurrent LN, evolving alternative drug options, and diagnostic work-up of thrombotic microangiopathy. Altogether, both documents provide an excellent guidance to the growing complexity of LN management. This article endeavours to prevent confusion by identifying differences and clarifying discrepancies.

Early-stage predictors for treatment responses in patients with active lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 283-289 ◽  
Author(s):  
G Liu ◽  
H Wang ◽  
J Le ◽  
L Lan ◽  
Y Xu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Serum Albumin ◽  
Immunosuppressive Therapy ◽  
Early Stage ◽  
Complement C3 ◽  
Class Iii ◽  
Class V ◽  
Predictive Values ◽  
Cutoff Value ◽  
Active Lupus Nephritis

Objective We analyzed data of lupus nephritis (LN) patients to find parameters that can predict remission. Methods Sixty-four LN patients who were diagnosed with class III, IV, V or V + III/IV by renal biopsy and were followed up for more than six months in our center were enrolled retrospectively. Receiver operating characteristic curves were used to test the predictive values of urinary protein-to-creatinine ratio (UPCR), serum albumin and complement C3 at the first, second and third months as predictors for remission at the sixth month. Results The patients' renal pathologies were class III (five cases), class IV (33 cases), class V (nine cases) and class V + III/IV (17 cases). All patients received standard immunosuppressive therapy. Forty-six (71.9%) patients (grouped as the remission group) achieved remission at the end of the sixth month, including 23 complete remissions and 23 partial remissions. The other 18 patients were grouped as the no-remission group. There were no significant differences in clinical data, proportion of immunosuppressive therapy or renal pathological characteristics between the remission group and no-remission group at baseline, except the serum urea nitrogen of the remission group was lower than in the no-remission group. The UPCR were significantly lower in the remission group than in the no-remission group at months 1, 2, 3 and 6, respectively, while the serum albumin was significantly higher in the remission group than in the no-remission group at months 3 and 6, respectively. There were no significant differences in serum creatinine between the remission group and no-remission group, except at month 1. The C3 levels were higher in the remission group than in the no-remission group at months 1, 2 and 3, respectively. The areas under the curve (AUC) of the change percentage of UPCR at month 3 and the serum albumin at month 3 were the most significant (AUC 0.778, p = 0.002; AUC 0.773, p = 0.001, respectively). The cutoff value of the change percentage of UPCR at month 3 was 59%. The cutoff value of serum albumin at month 3 was 32.9g/l. Conclusion The change percentage of UPCR ≥59% and the serum albumin ≥32.9 g/l at the third month were valuable for predicting remission at the sixth month in LN. Because of the small-size and retrospective nature, this study needs to be validated.

scholarly journals Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations

RMD Open ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e001263 ◽  
Author(s):  
Myrto Kostopoulou ◽  
Antonis Fanouriakis ◽  
Kim Cheema ◽  
John Boletis ◽  
George Bertsias ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Immunosuppressive Treatment ◽  
Class Iii ◽  
High Quality ◽  
Class V ◽  
High Quality Evidence ◽  
Optimal Duration ◽  
Quality Evidence

ObjectivesTo analyse the current evidence for the management of lupus nephritis (LN) informing the 2019 update of the EULAR/European Renal Association-European Dialysis and Transplant Association recommendations.MethodsAccording to the EULAR standardised operating procedures, a PubMed systematic literature review was performed, from January 1, 2012 to December 31, 2018. Since this was an update of the 2012 recommendations, the final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including literature prior to 2012.ResultsWe identified 387 relevant articles. High-quality randomised evidence supports the use of immunosuppressive treatment for class III and class IV LN (LoE 1a), and moderate-level evidence supports the use of immunosuppressive treatment for pure class V LN with nephrotic-range proteinuria (LoE 2b). Treatment should aim for at least 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (<500–700 mg/day) at 12 months (LoE 2a-2b). High-quality evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) as initial treatment of active class III/IV LN (LoE 1a). Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a). There is low-quality level evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease, all methods of kidney replacement treatment can be used, with transplantation having the most favourable outcomes (LoE 2b).ConclusionsThere is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment, but low-to-moderate quality evidence to guide treatment of class V LN, monitoring and optimal duration of immunosuppression.

CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis

2020 ◽  
Author(s):  
Matthieu Halfon ◽  
Delphine Bachelet ◽  
Guillaume Hanouna ◽  
Barbara Dema ◽  
Christophe Pellefigues ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Induction Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Diagnostic Study ◽  
Class Iii ◽  
Activation Markers ◽  
Class V ◽  
Fluorescent Intensity ◽  
Pre Treatment

Abstract Background Basophils were recently shown to contribute to lupus nephritis (LN). This study assessed blood basophil activation markers (BAMs) for the diagnosis of LN severity and as pre-treatment prognostic markers of the response to treatment in patients with severe LN. Method The diagnostic study included all the patients of a monocentric prospective observational cohort built with consecutive patients diagnosed with LN on the basis of a renal biopsy. The prognostic study selected patients of this cohort according to the following inclusion criteria: ≥18 years old, Class III or IV A ± C ± Class V or pure Class V LN at the time of inclusion and treated with an induction treatment for LN. Clinical data and BAMs were obtained at the time of the kidney biopsy. LN remission status was recorded 12 months after induction therapy initiation. Associations between baseline data and histological severity of LN or LN remission were assessed using logistic regression. Results No significant association was found between BAMs and the histological severity of LN in 101 patients. Among the 83 patients included in the prognostic study, 64 reached renal remission. CD62L expression on blood basophils at baseline was independently negatively associated with remission at 12 months [odds ratio = 0.26, 95% confidence interval 0.08–0.82, P = 0.02 for quantitative CD62L expression &gt;105 (geometric fluorescent intensity) gMFI]. CD62L &lt;105 gMFI was associated with a probability of 0.87 of LN remission in the next 12 months after the start of induction therapy. Conclusion Pre-treatment CD62L expression on blood basophils could be a first predictive biomarker of renal response to induction therapy at 12 months in patients with severe LN.

High Systemic Type I Interferon Activity is Associated with Active Class III/IV Lupus Nephritis

2021 ◽  
pp. jrheum.210391
Author(s):  
Taro Iwamoto ◽  
Jessica M. Dorschner ◽  
Shanmugapriya Selvaraj ◽  
Valeria Mezzano ◽  
Mark A. Jensen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Type I Interferon ◽  
Renal Tissue ◽  
High Serum ◽  
Complement C3 ◽  
Type I ◽  
Class Iii ◽  
Dsdna Antibody ◽  
The Impact ◽  
Active Class

Objective Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the impact of IFN in LN. Methods 221 systemic lupus erythematosus (SLE) patients were studied. Serum IFN activity was measured by WISH bioassay. mRNA in-situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, interferon-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C or BDCA2). Podocyte cell line gene expression was measured by real-time PCR. Results Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (OR=5.48, p=4.0x10-7). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely co-localized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. Conclusion Systemic high IFN is involved in the pathogenesis of severe LN. We do not find co-localization of pDCs with IFN signature in renal tissue, and instead observe the greatest intensity of IFN signature in glomerular areas, which could suggest a blood source of IFN.

scholarly journals P0266PREDICTIVE FACTORS OF COMPLETE RENAL RESPONSE IN PROLIFERATIVE LUPUS NEPHRITIS: A COLLABORATIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beatriz Sanchez Alamo ◽  
Clara Maria Cases Corona ◽  
Serena Gatius ◽  
Patricia Dominguez Torres ◽  
Elena Valdes ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Univariate Analysis ◽  
Immunosuppressive Treatment ◽  
Collaborative Study ◽  
Class Iii ◽  
Renal Response ◽  
Proliferative Lupus Nephritis

Abstract Background and Aims Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function. Method Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of &lt;25% of eGFR and the absence of proteinuria and microhematuria at the end of the follow up. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. We performed univariate analysis and logistic regression to identify independent risk factors. Results The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03]. In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments. Conclusion Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.

scholarly journals SAT0173 A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2019 UPDATE OF THE JOINT EUROPEAN LEAGUE AGAINST RHEUMATISM AND EUROPEAN RENAL ASSOCIATION–EUROPEAN DIALYSIS AND TRANSPLANT ASSOCIATION (EULAR/ERA-EDTA) RECOMMENDATIONS FOR THE MANAGEMENT OF LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1028.2-1028
Author(s):  
A. Fanouriakis ◽  
M. Kostopoulou ◽  
K. Cheema ◽  
G. Bertsias ◽  
D. Jayne ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Class Iii ◽  
Research Support ◽  
High Quality ◽  
Class V ◽  
High Quality Evidence ◽  
Optimal Duration ◽  
Quality Evidence

Background:Lupus nephritis (LN) affects ~ 40% of patients with systemic lupus erythematosus (SLE) and is associated with significant morbidity. New data has emerged since the publication of the EULAR/ERA-EDTA recommendations for the management of LN, involving a multidisciplinary panel of experts.Objectives:To analyze the current evidence, in order to inform the 2019 update of the EULAR/ERA-EDTA recommendations for the management of LN.Methods:According to the EULAR standardised operating procedures, a Medline systematic literature review (SLR) was performed, from January 2012 until 31 December 2018. The final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including the LoE of the 2012 recommendations.Results:We identified 542 relevant articles. High-quality evidence supports the use of immunosuppressive treatment for class III and IV LN (LoE 1a) there is moderate quality evidence for immunosuppression in pure class V LN, with nephrotic-range proteinuria (LoE 2b). Treatment should aim for a 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (< 500-700 mg/day) at 12 months (LoE 2a-2b). Strong evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) for the initial treatment of class III/IV LN (LoE 1a,Table); Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a,Table). There is little evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease due to LN, all methods of kidney replacement treatment have been used, but transplantation is accompanied by the most favourable outcomes (LoE 2b).Table.Randomized trials for induction therapy in LNConclusion:There is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment. There is low quality evidence to guide treatment of class V, monitoring and optimal duration of immunosuppression.Disclosure of Interests: :Antonis Fanouriakis Paid instructor for: Paid instructor for Enorasis, Amgen, Speakers bureau: Paid speaker for Roche, Genesis Pharma, Mylan, Myrto Kostopoulou: None declared, Kim Cheema: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Dimitrios Boumpas: None declared

Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction treatment of refractory lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1358-1362 ◽  
Author(s):  
D Jesus ◽  
M Rodrigues ◽  
J A P da Silva ◽  
L Inês
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Induction Therapy ◽  
Cyclosporine A ◽  
Induction Treatment ◽  
Class Iii ◽  
Class V ◽  
Renal Response ◽  
Prednisolone Dose ◽  
The Mean

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2–3 g and CsA was dosed up to 2.6–3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.

scholarly journals P0387PATHOLOGICAL FEATURES AND CLINICAL COURSE OF LATE-ONSET LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Amir Shabaka ◽  
Beatriz Sanchez Alamo ◽  
Serena Gatius ◽  
Clara Maria Cases Corona ◽  
Elena Valdes ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Early Onset ◽  
Kidney Biopsy ◽  
Clinical Course ◽  
Late Onset ◽  
Infectious Complications ◽  
Class V ◽  
Treatment Regimens ◽  
Histological Characteristics

Abstract Background and Aims It has been described that the early onset of lupus nephritis (LN) at a young age can determine the clinical course and outcome of the disease, being more aggressive with a higher mortality rate. However, no studies have explored the influence of age at onset of the disease in European cohorts of LN patients, neither have they analyzed treatment outcomes depending on age at presentation. Therefore, the aim of our study was to compare the clinical and histological characteristics of patients with late-onset LN compared to those with an onset at a younger age. Method We performed a retrospective observational study of biopsy-proven LN diagnosed between 1981 and 2018. Patients were stratified according to their age at presentation of LN, considering an onset with &gt;50 years old as late-onset. Demographic, clinical and serological data at presentation of systemic lupus and LN, during and at the end of follow-up, as well as extrarenal manifestations, histological characteristics of the kidney biopsy, clinical course, received treatment regimens and related adverse effects were registered. Results 85 LN patients were included in the study, 10 of whom had late-onset LN (11.7%). Late-onset LN patients presented significantly higher serum C3 and C4 levels at the time of kidney biopsy (92.8 ± 22.4 mg/dl vs 62.5 ± 25.7 mg/dl, p=0.002, and 18.6 ± 5.0 vs. 9.3±5.8 mg/dl, p&lt;0.001 respectively), and had lower eGFR measured by CKD-EPI (58.50±19.79 vs 90.41±30.53,p=0.003), a higher frequency of serositis manifestations (53.45% vs 17.46%, p=0.034), predominantly pleuritis (79.37% vs 51.75% p=0.013). Early-onset LN had predominantly Class IV LN (50% vs 10%, p=0.017), whereas in late-onset LN the most frequent type was Class V LN (50% vs 21.3%, p=0.048). Tubular atrophy was more common in late-onset LN (75% vs 34.9%, p=0.035). The group of patients with late-onset LN achieved complete clinical remission more frequently (87.5% vs 57.1%), but there were no differences in relapses between the groups. No differences were found in treatment regimens among the groups. Late-onset LN patients were more seronegative (100% vs 61.3%, p=0.015) at the end of follow-up. Severe infectious complications related to immunosuppression were significantly higher in late-onset LN patients (62.5% vs 22.2%, p=0.027) Conclusion Late-onset LN has a milder complement consumption at presentation compared to early-onset, and Class V LN is its most frequent form of presentation. Complete renal remission is more frequently achieved in late-onset LN compared to those with an early-onset, but present more adverse events associated with immunosuppression, particularly infectious complications.

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