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lupus nephritis treatment

Susan Yung, Claudia Yc Ng, Kin Yi Au, Kwok Fan Cheung, Qing Zhang, Chenzhu Zhang, Desmond Yh Yap, Mel Km Chau, Tak Mao Chan
Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody deposition on tubulo-interstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA antibodies on inflammatory processes in cultured proximal renal tubular epithelial cells (HK-2 cells) and their association with serum levels of IL-6, IL-8 and MCP-1 in patients. Binding of anti-dsDNA antibodies to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry...
October 25, 2016: Clinical Science (1979-)
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
Agnes Gardet, Wei C Chou, Taylor L Reynolds, Diana B Velez, Kai Fu, Julia M Czerkowicz, Jeffrey Bajko, Ann M Ranger, Normand Allaire, Hannah M Kerns, Sarah Ryan, Holly M Legault, Robert W Dunstan, Robert Lafyatis, Matvey Lukashev, Joanne L Viney, Jeffrey L Browning, Dania Rabah
Mouse models lupus nephritis (LN) have provided important insights into disease pathogenesis, although none have been able to recapitulate all features of the human disease. Using comprehensive longitudinal analyses, we characterized a novel accelerated mouse model of lupus using pristane treatment in SNF1 (SWR X NZB F1) lupus prone mice (pristane-SNF1 mice). Pristane treatment in SNF1 mice accelerated the onset and progression of proteinuria, autoantibody production, immune complex deposition and development of renal lesions...
2016: PloS One
Jan Klocke, Katharina Kopetschke, Anna-Sophie Grießbach, Valerie Langhans, Jens Y Humrich, Robert Biesen, Duska Dragun, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Renal infiltration of inflammatory cells contributes to the pathogenesis of Lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity...
October 18, 2016: European Journal of Immunology
Laura C Cappelli, Ami A Shah, Clifton O Bingham
Immune checkpoint inhibitors (ICIs) are newly approved treatments for advanced malignancies that are increasing survival. The mechanism of these drugs, non-specifically activating T cells, also leads to immune-mediated damage of tissue or immune-related adverse events (IRAE). IRAEs with rheumatic phenotypes are increasingly being recognised. Inflammatory arthritis, sicca syndrome, inflammatory myopathy, vasculitis and lupus nephritis have been described as a result of ICIs. Use of ICIs will be expanding in the coming years for several reasons...
2016: RMD Open
Chao-Yi Wu, Huang-Yu Yang, Tsung-Chieh Yao, Su-Hsun Liu, Jing-Long Huang
An urge of biomarker identification is needed to better monitor lupus nephritis (LN) disease activity, guide clinical treatment, and predict patient's long-term outcome. With the proinflammatory effect and its association with inflammasomes, the significance of interleukin-18 (IL-18) among pediatric-onset systemic lupus erythematous (pSLE) patient, especially, its importance in predicting long-term renal outcome was investigated.In a pSLE cohort of 96 patients with an average follow-up period of 10.39 ± 3...
October 2016: Medicine (Baltimore)
Stephen M Korbet, William L Whittier, Edmund J Lewis
BACKGROUND/AIM: We assess the impact of serum creatinine at baseline on complete remission rate and long-term outcome in severe lupus nephritis (SLN). METHODS: A total of 86 adult patients with SLN [International Society of Nephrology/Renal Pathology Society (ISN/RPS) class IV lesions] were evaluated based on baseline serum creatinine levels (≤1.0, 1.01-1.5, 1.51-2.0, 2.01-3.0, and >3.0 mg/dl; n = 22, 23, 16, 12, and 13, respectively). The complete remission rates (serum creatinine level of ≤1...
May 2016: Nephron Extra
Mahesh R Sigdel, Mukunda P Kafle, Dibya Singh Shah
BACKGROUND: The current standard for induction phase treatment of lupus nephritis is steroid combined with mycophenolate mofetil or pulse intravenous cyclophosphamide (IVC). The lowest dose of IVC recommended for induction therapy is that used in the Euro-Lupus Trial. It is not known whether same cumulative dose of IVC would be effective when given over six months. METHODS: We carried out a prospective, observational study on 41 patients of biopsy-proven lupus nephritis (class III, IV, V or mixed)...
October 7, 2016: BMC Nephrology
Kenneth Carekin Kalunian, Mimi Kim, Xianhong Xie, Amrutha Baskaran, Rossi Paola Daly, Joan Tenenbaum Merrill
OBJECTIVE: Most clinical trials for systemic lupus erythematosus (SLE) study the efficacy and safety of investigational agents added to variable background immunosuppressants, which has resulted in high response rates in patients treated with placebo plus standard of care (SOC) plus rescue measures. This project compared the impact of different SOC treatments and disease variables on the outcomes of SLE trials. MATERIAL AND METHODS: Data were obtained from 981 patients receiving only SOC treatments in three nephritis and three general SLE trials to compare response and flare rates on the basis of the British Isles Lupus Assessment Group (BILAG) index, a measure common to all trials...
March 2016: Eur J Rheumatol
Satoshi Suzuki, Shihoko Nakajima, Taiki Ando, Keisuke Oda, Manabu Sugita, Kunimi Maeda, Yutaka Nakiri, Yoshinari Takasaki
A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT...
2016: Case Reports in Rheumatology
Frank Ward, Joanne M Bargman
Membranous lupus nephritis (MLN) has a favorable prognosis compared to proliferative lupus nephritis (PLN) or combined MLN/PLN, although a significant proportion of cases will progress to end-stage kidney disease. There is considerable morbidity associated with thrombotic complications and treatment. Nondirected care includes renin-angiotensin-aldosterone system blockade, cardiovascular risk management, and antimalarial agents. There may be a role for corticosteroid monotherapy in some patients, but this requires further investigation...
September 20, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Monica Rydén-Aulin, Dimitrios Boumpas, Irene Bultink, Jose Luis Callejas Rubio, Luis Caminal-Montero, Antoni Castro, Agustín Colodro Ruiz, Andrea Doria, Thomas Dörner, Cristina Gonzalez-Echavarri, Elisa Gremese, Frederic A Houssiau, Tom Huizinga, Murat Inanç, David Isenberg, Annamaria Iuliano, Søren Jacobsen, Juan Jimenéz-Alonso, Lászlo Kovács, Xavier Mariette, Marta Mosca, Ola Nived, Joaquim Oristrell, Manuel Ramos-Casals, Javier Rascón, Guillermo Ruiz-Irastorza, Luis Sáez-Comet, Gonzalo Salvador Cervelló, Gian Domenico Sebastiani, Danilo Squatrito, Gabriella Szücs, Alexandre Voskuyl, Ronald van Vollenhoven
OBJECTIVES: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. METHODS: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy...
2016: Lupus Science & Medicine
Geetika Singh, Lavleen Singh, Ranajoy Ghosh, Devajit Nath, Amit Kumar Dinda
AIM: To describe the technique of immunofluorescence on paraffin embedded tissue sections and discuss the potential pitfalls with an in depth review of literature. METHODS: Immunofluorescence is integral to diagnostic renal pathology. Immunofluorescence on paraffin embedded renal biopsies (IF-P) after enzyme treatment has been described in literature, however has not found widespread use in renal pathology laboratories. In our laboratory proteinase K digestion of paraffin embedded renal biopsy material was standardized and applied prospectively in cases where immunofluorescence on fresh frozen tissue was non contributory or not possible...
September 6, 2016: World Journal of Nephrology
Y H Lee, G G Song
AIMS: This study aimed to assess the relative efficacy and safety of tacrolimus, mycophenolate mofetil (MMF), azathioprine (AZA), and cyclophosphamide (CYC) as maintenance therapy for lupus nephritis. METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of tacrolimus, MMF, AZA, and CYC for maintenance therapy in lupus nephritis patients were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs...
September 8, 2016: Zeitschrift Für Rheumatologie
Ranjan Gupta, Akhilesh Yadav, Amita Aggarwal
Urinary MCP-1 (uMCP-1) levels reflect lupus nephritis (LN) disease activity. However, long-term prospective studies evaluating it as a biomarker are lacking. SLE patients with active nephritis (AN), active disease without nephritis (ANR), and inactive disease (ID) were enrolled. AN patients were followed up every 3 months for 1 year. Urine and serum samples were collected at baseline from all and at follow-up visits in AN group. Urine samples from healthy subjects (HC), rheumatoid arthritis (RA), and diabetic nephropathy (DM) patients (20 each) served as controls...
November 2016: Clinical Rheumatology
Jasvinder A Singh, Alomgir Hossain, Ahmed Kotb, George Wells
BACKGROUND: To perform a systematic review and network meta-analysis (NMA) to compare the risk of serious infections with immunosuppressive medications and glucocorticoids in lupus nephritis. METHODS: A trained librarian performed two searches: (1) PubMed for all lupus nephritis trials from the end dates for the systematic review for the 2012 American College of Rheumatology (ACR) lupus nephritis treatment guidelines and the 2012 Cochrane Systematic Review on treatments for lupus nephritis, to September 2013; and (2) PubMed and SCOPUS for all lupus trials (excluding lupus nephritis) from inception to February 2014, to obtain additional trials for harms data in any lupus patient...
2016: BMC Medicine
Jasvinder A Singh, Alomgir Hossain, Ahmed Kotb, George A Wells
BACKGROUND: There is a lack of high-quality meta-analyses and network meta-analyses of immunosuppressive drugs for lupus nephritis. Our objective was to assess the comparative benefits and harms of immunosuppressive drugs and corticosteroids in lupus nephritis. METHODS: We conducted a systematic review and network meta-analysis (NMA) of trials of immunosuppressive drugs and corticosteroids in patients with lupus nephritis. We calculated odds ratios (OR) and 95 % credible intervals (CrI)...
2016: Systematic Reviews
M N Salem, H A Taha, M Abd El-Fattah El-Feqi, N N Eesa, R A Mohamed
BACKGROUND: Renal involvement in systemic lupus erythematosus (SLE), known as lupus nephritis (LN), is a common and severe complication and a major predictor of poor outcome. Long-term survival in SLE can be improved with early diagnosis and prompt treatment of LN. A number of biochemical markers are currently used to clinically assess disease activity in patients; however, they lack sensitivity and specificity for differentiating renal activity and damage in LN. A reliable clinical biomarker that can forecast LN flare and which could be sequentially followed would help to optimize initiation and escalation of therapy at the time of active or relapsing disease...
September 12, 2016: Zeitschrift Für Rheumatologie
G Camicia, S A Muñoz, A Allievi, A O Orden, S Perés Wingeyer, R Trobo, A Eimon, J C Barreira, E Schneeberger, J Sarano, J Hofman, G de Larrañaga, F Aranda
UNLABELLED: Objetives: Systemic lupus erythematosus is a multifactorial autoimmune disease and the glomerulonephritis is one of the most severe complications, which leads to severe persistent proteinuria, chronic renal failure, and end-stage renal disease. This multicenter study investigated the genetic associations of a non-synonymous single-nucleotide polymorphism in DNase I with the risk of lupus and its influence on development of nephropathy in an Argentinean population. METHODS: Using the Polymerase chain reaction restriction fragment length polymorphism method, the Q222R (+2373A→G; Gln244Arg) DNase I polymorphism was studied in 156 systemic lupus erythematosus patients and 170 healthy controls...
April 2016: Acta Reumatológica Portuguesa
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