In the United States, approximately 35% of adults with Systemic Lupus Erythematosus (SLE) have clinical evidence of nephritis at the time of diagnosis; with an estimated total of 50–60% developing nephritis during the first 10 years of disease [1–4]. The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians, and is higher in men than in women. Renal damage is more likely to develop in non-Caucasian groups [2–4]. Overall survival in patients with SLE is approximately 95% at 5 years after diagnosis and 92% at 10 years [5, 6]. The presence of lupus nephritis significantly reduces survival, to approximately 88% at 10 years, with even lower survival in African Americans [5, 6].

The American College of Rheumatology (ACR) last published guidelines for management of systemic lupus erythematosus (SLE) in 1999 [7]. That publication was designed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE. Recommendations for management of lupus nephritis (LN) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication, with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis. Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned. Since that time, many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published, some of which are high quality prospective trials, and some not only prospective but also randomized. Thus, the ACR determined that a new set of management recommendations was in order. A combination of extensive literature review and the opinions of highly qualified experts, including rheumatologists, nephrologists and pathologists, has been used to reach the recommendations. The management strategies discussed here apply to lupus nephritis in adults, particularly to those receiving care in the United States of America, and include interventions that were available in the United States as of April 2011.

While these recommendations were developed using rigorous methodology, guidelines do have inherent limitations in informing individual patient care; hence the selection of the term “recommendations.” While they should not supplant clinical judgment or limit clinical judgment, they do provide expert advice to the practicing physician managing patients with lupus nephritis.

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American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

https://ard.bmj.com/content/annrheumdis/78/6/736.full.pdf

2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

Objectives To develop recommendations for the management of adult and paediatric lupus nephritis (LN).

https://ard.bmj.com/content/annrheumdis/71/11/1771.full.pdf

Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis

142 Summary of Recommendation Statements 143 Chapter 1: Introduction 154 Chapter 2: General principles in the management of glomerular disease 156 Chapter 3: Steroid-sensitive nephrotic syndrome in children 163 Chapter 4: Steroid-resistant nephrotic syndrome in children 172 Chapter 5: Minimal-change disease in adults 177 Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults 181 Chapter 7: Idiopathic membranous nephropathy 186 Chapter 8: Idiopathic membranoproliferative glomerulonephritis 198 Chapter 9: Infection-related glomerulonephritis 200 Chapter 10: Immunoglobulin A nephropathy 209 Chapter 11: Henoch-Schönlein purpura nephritis 218 Chapter 12: Lupus nephritis 221 Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis 233 Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis 240 Methods for guideline development 243 Biographic and Disclosure Information 252

KDIGO Clinical Practice Guideline for Glomerulonephritis

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.

Systemic lupus erythematosus.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomized prospective trial comparing low-dose (LD) versus high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data regarding survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomized in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (11% vs 4%, 14% vs 11% and 5% vs 9%, respectively) nor did mean serum creatinine, 24-h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressants and blood pressure lowering drugs. We confirm, after 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy. CONCLUSION: Our data confirm that a LD IVCY regimen followed by AZA - the "Euro-Lupus regimen" - achieves good clinical results in the very long-term.

https://ard.bmj.com/content/annrheumdis/69/01/61.full.pdf

J-P Cosyns

Papers

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide