Lupus nephritis: An update on treatments and pathogenesis

Abstract

Immunosuppressive therapies for lupus nephritis (LN) have improved significantly over the past few decades, resulting in growing number of choices for treatment individualization and improved renal and patient outcomes. Corticosteroids combined with mycophenolate or cyclophosphamide induces a satisfactory response in a high proportion of Asian and Caucasian patients, but the rate of improvement varies considerably between patients. Relatively low disease flare rate was observed in Chinese patients receiving low‐dose prednisolone and mycophenolate maintenance. Short‐term results with calcineurin inhibitors (CNI) are encouraging, attributed both to their immunosuppressive efficacy and the action of these agents on podocyte biology leading to more rapid proteinuria suppression. Additional data, especially on the avoidance of nephrotoxicity and metabolic side effects, is required to facilitate selection of patients appropriate for this treatment. Modifications of standard regimens such as reducing corticosteroid exposure or using enteric‐coated mycophenolate might help reduce treatment‐related toxicities without compromising efficacy. While clinical outcomes of patients have improved with recent therapeutic advances, individual and ethnic variations in disease manifestations and treatment response, as well as the prevention of infections and long‐term complications still present challenges to frontline clinicians. Recent data from histological examination and translational studies also suggest that complement activation via the alternative pathway, immune deposition on renal tubular basement membrane, and local inflammatory responses involving resident kidney cells are of pathogenic relevance in LN. The progress of clinical and translational studies has improved not only the understanding of disease mechanisms but also clinical decision making in the management of LN.

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

“…Systemic lupus erythematosus (SLE) is a complicated and multisystem autoimmune disease [1][2][3]. Lupus nephritis (LN) is a serious and common manifestation of SLE, and is characterized by autoantibody-mediated activation of inflammatory response in the kidney [2,4,5]. About 35% of patients show LN symptoms when SLE is diagnosed and 50-60% will develop LN during the first 10 years of disease [6,7].…”

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

“…5), pyuria (≥ 5 white blood cells/high-power field) and casts (composed of heme, granule, or red blood cells). The scale of each parameter was 0 or 4, and total rSLEDAI score were 0, 4, 8, 12, or 16[31].…”

Educational Case: Lupus Nephritis as an Example of Immune Complex–Mediated Glomerulonephritis

“…6,7 There is also some evidence to suggest that the alternative complement pathway plays a role in the pathogenesis of lupus nephritis. 8…”

“…2,9 It is important to prevent renal injury, to the greatest extent possible, since the development of chronic kidney disease in patients with systemic lupus erythematosus is linked to higher mortality risk. 8 Once the severity and activity of lupus nephritis and the extent of chronic damage to the kidney has been determined, 9 anti-inflammatory and immunosuppressive agents are a mainstay of therapy. Anti-inflammatory agents can help attenuate the immune response to the deposition of Ag-Ab complexes in the kidney and other affected organs, thereby reducing inflammation and hopefully preventing long-term organ damage.…”