Management Of Lupus Nephritis Research Articles

Management of lupus nephritis in children needs special considerations, but more paediatric data are required

Management of lupus nephritis in children needs special considerations, but more paediatric data are required

Role of Surveillance Kidney Biopsy in Management of Lupus Nephritis

Role of Surveillance Kidney Biopsy in Management of Lupus Nephritis

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An article reviews current management of lupus nephritis according to the KDIGO 2024 clinical practice guidelines.

KDIGO 2024 Clinical Practice Guideline for the management of lupus nephritis. Translated into Russian by E.V. Zakharova

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Management of Lupus Nephritis represents a focused update of the Lupus nephritis chapter from the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. The aim is to assist clinicians caring for individuals with lupus nephritis. The update takes into consideration evidence from randomized controlled trials published since February 2022. As in 2021, the chapter follows the same template, providing guidance related to diagnosis, treatment, and special situations. Based on the evidence, this update is focused on guidance related to treatment of lupus nephritis. This guideline update followed an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the strength of recommendations and certainty of the evidence following the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach. Limitations of the evidence are discussed and areas of future research are presented.

Serum DNase1, sTNFR1 and sTNFR2 as Risk Factors for Lupus Nephritis in Systemic Lupus Erythematosus Patients

BACKGROUND: Early detection and management of lupus nephritis (LN) in systemic lupus erythematosus (SLE) are essential to prevent irreversible kidney damage and improve patient outcomes; therefore, identifying reliable biomarkers to predict LN is paramount. However, there are still relatively few studies examining the potential biomarkers for LN in SLE patients. This study was conducted to investigate serum deoxyribonuclease I (DNase), soluble tumor necrosing factor 1 (sTNFR1) and soluble tumor necrosing factor 2 (sTNFR2) as a risk factor for LN in SLE patients.METHODS: A case-control study involving SLE patients aged 20-60 years was conducted. Blood was withdrawn from each subject for the measurement of serum level of DNase1, sTNFR1, and sTNFR2 that was performed using enzyme-linked immunoassay (ELISA) methods. Data was then analyzed using Chi-Square test and logistic regression tests.RESULTS: A total of 22 patients with LN and 22 without LN were included. The cut-off value for DNase1, sTNFR1, and sTNFR2 were 5.05 ng/mL, 6.52 ng/mL, and 7.02 ng/mL, respectively. The risk factors of LN in SLE patients were the low level of serum DNase1 (aOR=6.64; 95%CI: 1.25-35.29; p=0.026), low level of serum sTNFR1 (aOR=8.12; 95% CI: 1.56-42.10; p=0.013), and low level of serum sTNFR2 (aOR=5.57; 95%CI: 1.03-30.11; p=0.046).CONCLUSION: Serum DNase1 lower than 5.05 ng/mL, sTNFR1 lower than 6.52 ng/mL, and sTNFR2 lower than 7.02 ng/mL were risk factors for lupus nephritis in SLE patients. Hence, serum DNase1, sTNFR1 and sTNFR2 could be used as risk factors predictors for LN in SLE patients.KEYWORDS: DNase1, sTNFR1, sTNFR2, SLE, lupus nephritis

Unforeseen Detection of Klinefelter Syndrome During the Management of Lupus Nephritis in An Adolescent– a Case

Autoimmune disease is common in males with Klinefelter syndrome (KS) as testosterone deficiency predisposes them to the disease. A 20-year-old male who was diagnosed with lupus nephritis and he presented with bilateral progressive gynecomastia associated with signs of hypogonadism. Further workup confirmed the incidental diagnosis of Klinefelter syndrome (KS). This case illustrates the importance of investigating the cause of hypogonadism in males with autoimmune disease as early treatment with testosterone therapy can be beneficial in treating the clinical disease and preventing complications.

Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

IntroductionCurrent therapeutic management of lupus nephritis (LN) fails to induce long-term remission in over 50% of patients, highlighting the urgent need for additional options. MethodsWe analysed differentially expressed genes in peripheral blood from active LN (n=41) and active non-renal lupus (n=62) patients versus healthy controls (n=497) from the European PRECISESADS project (NTC02890121), and dysregulated gene modules in a discovery (n=26) and a replication (n=15) set of active LN cases. ResultsReplicated gene modules qualified for correlation analyses with serological markers, and regulatory network and druggability analysis. Unsupervised co-expression network analysis revealed 20 dysregulated gene modules and stratified the active LN population into three distinct subgroups. These subgroups were characterised by low, intermediate, and high interferon (IFN) signatures, with differential dysregulation of the “B cell” and “plasma cells/immunoglobulins” modules. Drugs annotated to the IFN network included CC-motif chemokine receptor 1 inhibitors, programmed death-ligand 1 inhibitors, and irinotecan, while the anti-CD38 daratumumab and proteasome inhibitor bortezomib showed potential for counteracting the “plasma cells/immunoglobulins” transcriptomic signature. In silico analysis demonstrated the low-IFN subgroup to benefit from calcineurin inhibition and the intermediate-IFN subgroup from B cell targeted therapies. High-IFN patients exhibited greater anticipated response to anifrolumab while daratumumab appeared beneficial for the intermediate-IFN and high-IFN subgroups. ConclusionIn summary, IFN upregulation and B and plasma cell gene dysregulation patterns revealed three LN patient subgroups, which may not necessarily represent distinct disease phenotypes but rather phases of the inflammatory processes during a renal flare, providing a conceptual framework for precision medicine in LN.

Insights into future management of lupus nephritis

Lupus nephritis (LN) is a common and serious manifestation of systemic lupus erythematosus and is a major cause of mortality and morbidity. The current standard-of-care treatment for LN include conventional immunosuppressive treatments such as mycophenolate mofetil, cyclophosphamide, or azathioprine, combined with glucocorticoids. However, this treatment approach has several unmet needs, such as achieving only modest remission rates, potential toxicities, and prolonged cumulative steroid exposure, resulting in suboptimal patient outcomes. The LN treatment landscape is evolving rapidly to meet these unmet needs, with belimumab and voclosporin being the first drugs approved specifically for treatment of LN in 2020 and 2021, respectively. Here, we review the likely roles in LN therapy for several targeted therapies, including select therapies under investigation, and interventions in early development such as therapies targeting B cells (obinutuzumab, atacicept, ianalumab, and CD19 chimeric antigen T-cell therapy), inflammatory cytokines (secukinumab and anifrolumab), and the immunoproteasome (zetomipzomib); we also review treatment strategies designed to minimize steroid exposure. Treatments in development have demonstrated encouraging short- and long-term efficacy and steroid-sparing potential, potentially paving the way for improved treatment regimens and patient outcomes in LN.

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review.

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, theexact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.

EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis— the European Renal Association (ERA) — Immunonephrology Working Group (ERA-IWG) perspective

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EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis: the European Renal Association-Immunonephrology Working Group (ERA-IWG) perspective.

EULAR 2023 recommendations for SLE treatment: synopsis for the management of lupus nephritis: the European Renal Association-Immunonephrology Working Group (ERA-IWG) perspective.

Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis.

Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney's filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations. Voclosporin (VOC), a novel CNI, no longer requires drug level monitoring and seems to lack these adverse effects, although hypertension and drug-drug interactions still occur. VOC demonstrated efficacy superior to standard-of-care in controlling active lupus nephritis in the phase 2 AURA-LV and the phase 3 AURORA-1 trials and was approved for the treatment of active lupus nephritis. However, how to implement VOC into the current and changing treatment landscape of lupus nephritis is still debated. Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL). These include: 1. patient stratification to either VOC or BEL, 2. VOC/BEL combination therapy, 3. VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.

Management of Lupus Nephritis: New Treatments and Updated Guidelines.

Management of lupus nephritis (LN) has evolved considerably over the past years. Here we provide a comprehensive review of clinical trials that form the basis for the KDIGO and EULAR/ERA-EDTA updated guidelines and present-day trials that will change the landscape of LN therapy in years to come. Additionally, we highlight issues related to cost of therapy, resistant disease, and downstream adverse effects of specific therapies.

OA01 A case report of a patient with Type 1 diabetes mellitus and systemic lupus erythematosus: a management dilemma

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. Up to 30% of patients with SLE will develop other autoimmune conditions. A few cases of SLE and Type 1 Diabetes Mellitus (T1DM) have been reported in literature. Corticosteroids which is key in induction therapy increases the risk of hyperglycemia and hypertension. Other immunosuppressive agents such as mycophenolate mofetil used in management of lupus nephritis increase the risk of hyperglycemia. This poses a challenge in the management of SLE in a patient with T1DM. Aim To describe a management dilemma in caring for a child with T1DM and SLE at a tertiary referral teaching hospital in Nairobi, Kenya. Method Retrospective chart review of a child with T1DM and SLE at Aga Khan University Medical College East Africa, Nairobi, Kenya. Results We discuss a 16-year-old male patient with T1DM since nine years of age on insulin and on follow up in the endocrine clinic. He presented with complaints of facial and lower limb swelling of three days and severe frontal headache associated with nausea for one day. He was also noted to have a strong family history of Sjogren’s disease and diabetes. His initial examination revealed hypertension with a blood pressure of 184/118 mmHg, facial and lower limb oedema. He was commenced on labetalol infusion and amlodipine for blood pressure control, and was to continue with his insulin regimen. Initial urinalysis showed proteinuria and hematuria. An impression of hypertensive emergency with nephropathy was made. Rheumatology review was requested. Investigations revealed an ANA titer of > 1:1280; anti-smith and anti dsDNA antibodies were positive; low C3 and low C4. Echo showed pleural effusion. The kidney biopsy showed features of proliferative lupus nephritis class IV with no features of diabetic nephropathy. A diagnosis of SLE was made and management initiated with hydroxychloroquine, methylprednisolone for three days then oral prednisolone and mycophenolate mofetil. During methylprednisolone therapy, the patient was noted to have unrecordably high blood glucose necessitating an insulin infusion for six days and close adjustment of insulin doses by the endocrinologist. Initially, after the 1st dose of methylprednisolone, his blood pressure seemed to improve. During the course of treatment, his blood pressure was elevated and difficult to control despite being on labetalol infusion, amlodipine, enalapril and carvedilol. Adjustment of antihypertensive drug doses and addition of hydralazine were made by the nephrologist, cardiologist and critical care specialist. He was eventually discharged with controlled blood glucose and blood pressure. He is currently doing well and is on follow up in the nephrology, rheumatology and endocrinology clinics. Conclusion Our case report highlights the challenges that arise while managing patients with SLE and other illnesses such as T1DM. It also points out the necessity of multi-disciplinary care. This may be a challenge in many African health facilities due to a low number of specialized doctors.

Novel Therapeutics for Management of Lupus Nephritis: What Is Next?

Lupus nephritis is a severe, organ-threatening manifestation of systemic lupus erythematosus. The current standard of care in the treatment of lupus nephritis is limited to broad-spectrum immunosuppressants, which have significant concerns of short- and long-term toxicity. With traditional approaches, kidney survival and patient outcomes have remained suboptimal. Robust research in the therapeutics of lupus nephritis has resulted in development of many novel drugs targeting specific inflammatory response pathways. Some newer agents have shown a definitive signal of benefit when added to standard of care. With the advent of precision medicine in nephrology, lupus nephritis treatment may undergo a shift toward incorporating approaches using these newer drugs and individualizing care of our patients. This review highlights major advances in management of lupus nephritis over the last 25 years and explores the ongoing trials of emerging therapies in lupus nephritis.

#6843 CITATION CLASSICS IN LUPUS NEPHRITIS: A BIBLIOMETRIC ANALYSIS

Abstract Background and Aims Lupus nephritis is an important risk factor for morbidity and mortality in systemic lupus erythematosus. During the past three decades, extensive research has been done to address this important complication and devise better management strategies. In this article we aimed to perform a thorough assessment of the research productivity in lupus nephritis by identifying the 100 most-cited articles in lupus nephritis. Methods The top 100 most-cited English language articles on lupus nephritis from 1990 were examined by bibliometric analysis from the Google Scholar database of ‘Harzing's Publish or Perish’ software. These articles were subsequently analysed in detail and the chief characteristics are presented here. Results From 1990-2022, there were 111358 citations with 3480 cites/year and an average of 111 cites/paper. Thirty articles had greater than 400 citations, with 9 having more than1000 citations. Majority of the publications were from the United States of America (46%) with maximum publications from the National Institute of Health (NIH), Bethesda. Among these 100 most-cited articles, there were a median of 7 (5-12) authors per article with a mean of 9.6 authors. Twenty-six percent of the top-100 most-cited articles were randomized controlled trials while cohort and in-vivo studies addressing pathophysiology and biopsy related data accounted for one-fourth each. Among rheumatology journals, ‘Arthritis Rheum’, ‘Ann Rheum Dis’ and ‘Lupus’ were the most preferred journals for researchers working on lupus nephritis. Conclusion This article gives an overview of the research productivity, landmark publications and emerging trends in lupus nephritis. Increased emphasis on high-quality data from randomized controlled trials is revolutionising the management of lupus nephritis.

Four trajectories of 24-hour urine protein levels in real-world lupus nephritis cohorts

ObjectivesA 24-hour urine protein (24hUP) is a key measurement in the management of lupus nephritis (LN); however, trajectories of 24hUP in LN is poorly defined.MethodsTwo LN cohorts that underwent renal...

Immunological and translational key challenges in systemic lupus erythematosus: A symposium update

The first LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium convened on December 16, 2022 in Toulouse, France to address challenging questions in systemic lupus erythematosus (SLE). Special focus was put on (i) the role played by genes, sex, TLR7, and platelets on SLE pathophysiology; (ii) autoantibodies, urinary proteins, and thrombocytopenia contribution at the time of diagnosis and during follow-up; (iii) neuropsychiatric involvement, vaccine response in the COVID-19 era, and lupus nephritis management at the clinical frontline; and (iv) therapeutic perspectives in patients with lupus nephritis and the unexpected adventure of the Lupuzor/P140 peptide. The multidisciplinary panel of experts further supports the concept that a global approach including basic sciences, translational research, clinical expertise, and therapeutic development have to be prioritized in order to better understand and then improve the management of this complex syndrome.

Lupus Nephritis: Current Perspectives and Moving Forward.

Lupus nephritis is a severe organ manifestation of systemic lupus erythematosus, and its pathogenesis involves complex etiology and mechanisms. Despite significant knowledge gains and extensive efforts put into understanding the development and relapsing disease activity, lupus nephritis remains a substantial cause of morbidity and mortality in lupus patients. Current therapies retain a significant unmet medical need regarding rates of complete response, preventing relapse of lupus nephritis, progression of chronic kidney disease to kidney failure, drug toxicity, and pill burden-related drug non-adherence. Connected to progression of chronic kidney disease are the associated risks for disabling or even lethal cardiovascular events, as well as chronic kidney disease-related secondary immunodeficiency and serious infections. In this regard, biomarkers are needed that can predict treatment response to specific drugs to enable personalized precision medicine. A series of clinical trials with innovative immunomodulatory drugs are ongoing and raise expectations for improvements in the management of lupus nephritis. Here, we review how new developments in pathogenesis connect with current and future perspectives for the management of lupus nephritis.

Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III–IV and 21.4% have class V. Around 67.5% of patients with LN classes III–IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III–IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III–IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.