Systemic Lupus Erythematosus
Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide in Clinical Innovation in Rheumatology, 2023
Despite pulse steroids demonstrating efficacy in lupus nephritis, the need for steroid-sparing therapies for SLE and lupus nephritis is obvious. Of interest, it was the first drug used for SLE that was first shown to be effective in an SLE mouse model. Shortly thereafter, several clinical studies demonstrated the efficacy of prednisone plus either cyclophosphamide (CYC) or azathioprine (AZA) compared to prednisone alone. Therefore, in 1986 the NIH investigated comparing cyclophosphamide and prednisone. This study showed better renal function in patients treated with CYC compared to those with oral prednisone. This benefit was preserved in patients with high-risk disease, which included signs of irreversible renal parenchymal destruction and active lupus glomerulonephritis.60 Likely related to issues with clinical trial study design and a desire to see results quickly, FDA approval for cyclophosphamide and other oral disease-modifying agents was not successful. Nonetheless, many studies reproduced similar results with cyclophosphamide, and this treatment remained a popular choice for lupus nephritis for many years. However, there remained concerns over its severe toxic effects, including hemorrhagic cystitis, bone marrow suppression, malignancy, opportunistic infections, and premature gonadal failure. Hence, investigators began looking into safer medications that could be used for induction therapy, leading to a comparison between mycophenolate mofetil (MMF) and CYC.61
Autoimmune Disorders across the Lifespan
Michelle Tollefson, Nancy Eriksen, Neha Pathak in Improving Women's Health Across the Lifespan, 2021
SLE is a Th2-mediated autoimmune disorder and is a chronic multisystem inflammation of the skin, joints, kidney, and brain that can be intermittent, constant, active, or quiescent. Its cause is not fully known. The incidence of SLE in the United States is 0.1%. Approximately 90% of those affected are women, predominately of childbearing age, and of African-American descent. About 10–12% of patients with SLE have a positive family history. Clinical symptoms consist of the lupus triad of fever, joint pain, and rash. Photosensitivity and ultraviolet exposure are the most widely accepted triggers associated with development and flares of SLE. Lupus nephritis is among the most common clinical complications and occurs in up to 74% of patients, accounting for significant morbidity and mortality particularly among ethnic minorities.14
Connective tissue
Brian J Pollard, Gareth Kitchen in Handbook of Clinical Anaesthesia, 2017
SLE is more common in females than males (9:1), and the usual onset is in the third and fourth decades. It is an episodic disease with periods of prolonged remission punctuated by life-threatening exacerbations. Usually the onset involves arthralgia, fever, weight loss, rash, anaemia and leucopaenia; involvement of other organs produces a wide clinical spectrum of disease (Table 9.4). The presence of lupus nephritis indicates a poor long-term prognosis although most deaths are a result of cardiovascular complications: the risk of myocardial infarction is 50 times greater in SLE than the age/sex-matched general population. Many patients with SLE have subclinical atherosclerosis but the mechanisms underlying the increased cardiovascular risks are not fully understood.
Pathological mechanisms of abnormal iron metabolism and mitochondrial dysfunction in systemic lupus erythematosus
Published in Expert Review of Clinical Immunology, 2021
Chris Wincup, Natalie Sawford, Anisur Rahman
One particular example in which abnormal iron metabolism and mitochondrial dysfunction may occur is within the kidney. Lupus nephritis is a serious manifestation of the disease, which if not promptly identified and adequately treated can result in irreversible damage and in some cases lead to end-stage renal failure [requiring renal replacement therapy]. The most common cause of renal injury is glomerulonephritis, in which there is inflammation within the glomerulus. This is an important site of nutrient reabsorption and as such has the highest concentration of mitochondria within the kidney [75]. At present, very little is known with regards to the precise way in which the glomerulus handles circulating iron but previous studies have noted that podocytes [a specialist glomerular epithelial cell type found within Bowman’s capsule] are capable of taking up iron bound to transferrin and store it as ferritin [76]. As a result, some authors have proposed elevated urinary transferrin levels to be a useful biomarker of potentially active lupus nephritis [77].
Systemic lupus erythematosus: nothing stale her infinite variety
Published in Modern Rheumatology, 2018
Renal disease develops in more than half of SLE patients, and represents the first clinical manifestation of SLE in 15–20% [31]. Lupus nephritis is an important cause of morbidity and even mortality in patients with SLE and has diverse morphologic manifestations with varying clinical presentations and consequences. The pathogeneses vary involving immune complex deposit, endothelial injury, podocytopathy or tubulointerstitial injury thus leading to various prognosis with different pathological findings. Lupus nephritis is, by definition, an IgG dominant immune complex disease and the pattern/location of the deposition determines the resulting histopathological pattern. The varying glomerular immune complex patterns are diagnosed according to the International Society of Nephrology-Renal Pathological Society modification of the WHO criteria (ISN/RPS) classification that include predominantly mesangial deposits (classes I and II), subendothelial deposits with endocapillary hypercellularity or prominent duplication of glomerular basement membranes, often with necrotizing and crescentic lesions (classes III and IV, focal and diffuse) or membranous forms (class V). Renal biopsy plays a crucial role in the diagnosis of the specific form of lupus nephritis in the diagnosis of both SLE and lupus nephritis as well as determining the treatment strategy of the disease [32]. Immuno-suppressive therapy is essential for active lesions and physician need to be aware that it has minimal effect on scarring and involves considerable toxicity.
Study of urinary interferon gamma-induced protein 10 (IP-10) and urinary soluble CD 25 (sCD25) as markers of lupus nephritis and their relation to histological class
Published in Alexandria Journal of Medicine, 2018
Montasser Mohamed Hussein Zeid, Nahed Mohamed Baddour, Dalia Abd El-Moaty El-Neily, Heba Selim Elshair, Mohamed Mamdouh
Similar findings of urinary IP-10 in lupus nephritis were reported by Marie et al.25 in their study which included thirty patients with lupus nephritis and another 30 without evidence of lupus nephritis. Avihingsanon et al.26 studied 26 patients with LN. They examined the urinary mRNA levels of IP-10, CXCR3, transforming growth factor-β (TGF-β), and vascular endothelial growth factor and concluded that class IV lupus nephritis patients had higher levels than other classes. Also, Abujam et al.27 studied 136 patients with SLE from whom 78 were active (46 active renal and 32 active non-renal) finding no difference in serum levels of monocyte chemoattractant protein 1(MCP-1) and IP-10 between active renal and active non-renal SLE; only urinary levels were higher. It seems that the increased urinary excretion of IP-10 in active LN is mainly due to active local inflammation in the kidneys.
Related Knowledge Centers
- Glomerulus
- Inflammation
- Ultrasound
- Autoimmune Disease
- Kidney
- Lupus
- Glomerulonephritis
- Blood Test
- Urinalysis
- Renal Biopsy