The Experts below are selected from a list of 35148 Experts worldwide ranked by ideXlab platform
Brad H. Rovin - One of the best experts on this subject based on the ideXlab platform.
-
Update on Lupus Nephritis
Clinical journal of the American Society of Nephrology : CJASN, 2016Co-Authors: Salem Almaani, Alexa Meara, Brad H. RovinAbstract:SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus Nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for Lupus Nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with Lupus.
-
Current and Emerging Therapies for Lupus Nephritis
Journal of the American Society of Nephrology : JASN, 2016Co-Authors: Samir V. Parikh, Brad H. RovinAbstract:The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative Lupus Nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing Lupus Nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of Lupus Nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of Lupus Nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for Lupus Nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care Lupus Nephritis treatments.
-
Lupus Nephritis induction therapy in severe Lupus Nephritis should mmf be considered the drug of choice
Clinical Journal of The American Society of Nephrology, 2013Co-Authors: Brad H. Rovin, Tak Mao Chan, Samir Parikh, Lee A Hebert, C C Mok, Ellen M Ginzler, Lai Seong Hooi, Paul G Brunetta, Romeo Maciuca, Neil SolomonsAbstract:Summary Severe Lupus Nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe Lupus Nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe Lupus Nephritis. We performed a systematic review of the outcomes of treating severe Lupus Nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe Lupus Nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe Lupus Nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolatemofetilandcyclophosphamideareaboutequalininducingremission.However,long-termoutcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe Lupus Nephritis. Clin J Am Soc Nephrol 8: ccc–ccc, 2013. doi: 10.2215/CJN.03290412
-
Lupus Nephritis: guidelines for Lupus Nephritis--more recommendations than data?
Nature reviews. Nephrology, 2012Co-Authors: Brad H. RovinAbstract:Several management guidelines for Lupus Nephritis have been published this year. All of the guidelines provide clear and consistent recommendations, but although evidence-based, many of the recommendations are not supported by high-quality clinical data. The guidelines reveal these evidence gaps and are thus an important roadmap for future Lupus Nephritis clinical research.
Hans-joachim Anders - One of the best experts on this subject based on the ideXlab platform.
-
Treatment Options for Refractory Lupus Nephritis
Clinical journal of the American Society of Nephrology : CJASN, 2019Co-Authors: Hans-joachim Anders, Falk HiepeAbstract:Lupus Nephritis, one of several organ manifestations of SLE, affects mostly young women and imposes a risk to develop ESKD and premature cardiovascular disease. Every episode or flare of Lupus Nephritis implies irreversible nephron loss and therefore, shortens kidney lifespan ([1][1]). Only
-
Immunopathology of Lupus Nephritis
Seminars in Immunopathology, 2014Co-Authors: Hans-joachim Anders, Agnes B. FogoAbstract:When patients with systemic Lupus erythematosus (SLE) present with urinary abnormalities, a renal biopsy is usually needed to rule out or confirm Lupus Nephritis. Renal biopsy is also needed to define the type of renal manifestation as different entities are associated with different outcomes; hence, renal biopsy results shape Lupus management. But why does Lupus Nephritis come in different shapes? Why do patients with SLE often show change over time in class of Lupus Nephritis or have mixed forms? How does autoimmunity in SLE evolve? Why does loss of tolerance against nuclear antigens preferentially affect the kidney? Why are immune complex deposits in different glomerular compartments associated with different outcomes? What determines crescent formation in Lupus? In this review, we discuss these questions by linking the latest information on Lupus pathogenesis into the context of the different classes of Lupus Nephritis. This should help the basic scientist, the pathologist, and the clinician to gain a more conceptual view on the immunopathology of Lupus Nephritis.
-
The pathogenesis of Lupus Nephritis.
Journal of the American Society of Nephrology : JASN, 2013Co-Authors: Maciej Lech, Hans-joachim AndersAbstract:Lupus Nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of Lupus Nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic Lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic Lupus resemble those of viral infection. In Lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of Lupus Nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to Lupus Nephritis and provide the rationale for the latest and novel treatment strategies.
-
Lupus Nephritis: Implications of the new ACR Lupus Nephritis guidelines.
Nature reviews. Nephrology, 2012Co-Authors: Hans-joachim Anders, Gerald B. AppelAbstract:The American College of Rheumatology recently published guidelines for the screening, treatment, and management of Lupus Nephritis. How will or should these guidelines impact our current daily practice?
Liz Lightstone - One of the best experts on this subject based on the ideXlab platform.
-
Lupus Nephritis and Pregnancy: Concerns and Management
Seminars in nephrology, 2017Co-Authors: Liz Lightstone, Michelle A. HladunewichAbstract:Pregnancy associated with Lupus, especially Lupus Nephritis, is often fraught with concern for both the mother and fetus. Thus, it is paramount that care begins preconception so that proper planning in terms of optimizing the medical regimen, discontinuation of fetotoxic agents, and treatment of active disease can occur. It is well known that active Nephritis at the time of conception is associated with poor outcomes. Even with quiescent disease, recent data indicate that being Lupus anticoagulant-positive, nonwhite or Hispanic, and using antihypertensive medications were all predictors of worse pregnancy outcomes. Further, prior Lupus Nephritis also predicts higher rates of preeclampsia and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Differentiating Lupus Nephritis from preeclampsia often presents as a conundrum, but Lupus Nephritis can be confirmed by the presence of decreasing complement levels and increasing double-stranded DNA (dsDNA) antibody levels in addition to new onset hypertension and proteinuria. We hope that the more mechanistic approach of measuring angiogenic markers, which are diagnostic for preeclampsia, will be the standard of care in the future. Women with Lupus and prior Lupus Nephritis can have successful pregnancies, but outcomes are dependent on "the art of planning" as well as close communication between the obstetrician, the nephrologist, and the rheumatologist.
-
Lupus Nephritis management guidelines compared
Nephrology Dialysis Transplantation, 2016Co-Authors: Suzanne Wilhelmus, Dimitrios T. Boumpas, Liz Lightstone, Ingeborg M Bajema, George Bertsias, Caroline Gordon, Vladimir Tesar, David JayneAbstract:In the past years, many (randomized) trials have been performed comparing the treatment strategies for Lupus Nephritis. In 2012, these data were incorporated in six different guidelines for treating Lupus Nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of Lupus Nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature.
-
Lupus Nephritis: where are we now?
Current opinion in rheumatology, 2010Co-Authors: Liz LightstoneAbstract:Purpose of reviewTo consider the challenges in the management of Lupus Nephritis with respect to diagnosis and optimal therapy for induction and maintenance of response.Recent findingsDespite several large clinical trials in Lupus Nephritis, no second line drug is licensed for use in induction of re
Chi Chiu Mok - One of the best experts on this subject based on the ideXlab platform.
-
Con: Cyclophosphamide for the treatment of Lupus Nephritis
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2016Co-Authors: Chi Chiu MokAbstract:Kidney involvement is a major determinant for morbidity and mortality in patients with systemic Lupus erythematosus. The treatment target of Lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of Lupus Nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of Lupus Nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of Lupus Nephritis. Although MMF as induction-maintenance therapy has been increasingly used in Lupus Nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of Lupus Nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of Lupus Nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with Lupus Nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of Lupus Nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomeruloNephritis or as salvage therapy for recalcitrant disease.
-
Mycophenolate mofetil for Lupus Nephritis: an update.
Expert review of clinical immunology, 2015Co-Authors: Chi Chiu MokAbstract:Renal disease in systemic Lupus erythematosus carries significant morbidity and mortality. Intensive immunosuppression to dampen kidney inflammation timely and maintenance therapy to prevent renal flares is necessary to reduce the long-term risk of renal failure. Mycophenolate mofetil (MMF) has emerged to be the first-line treatment of Lupus Nephritis for its better safety profile compared with cyclophosphamide. In controlled trials, MMF is non-inferior to cyclophosphamide for induction therapy but is superior to azathioprine as maintenance therapy. Although biologics have shown promise in refractory Lupus Nephritis, combining MMF with a number of novel biological agents does not enhance the therapeutic efficacy. Recently, low-dose combination of MMF and tacrolimus has been shown to be more efficacious than intravenous pulse cyclophosphamide in inducing remission of Lupus Nephritis in Chinese patients. Therapeutic monitoring of the serum mycophenolic acid level to enhance the efficacy of MMF in Lupus Nephritis is being explored.
-
Therapeutic Options for Resistant Lupus Nephritis
Seminars in arthritis and rheumatism, 2006Co-Authors: Chi Chiu MokAbstract:Objectives To summarize the therapeutic options for proliferative and membranous Lupus Nephritis that is resistant to conventional treatment. Methods Treatment trials in human Lupus Nephritis from years 1985 to 2005 that have been published in the English literature were searched by Medline using the keywords "Lupus," "Nephritis," "glomeruloNephritis," "renal," "refractory," "resistant," "recalcitrant," "cyclophosphamide," "mycophenolate," "cyclosporin," "tacrolimus," "leflunomide," "intravenous immunoglobulin," "apheresis," "plasmapheresis," "immunoadsorption," "marrow transplantation," "stem cell transplantation," "immunoablative," "rituximab," and "biologics." Laboratory, histological, and nonrenal Lupus studies were excluded. Results There is no universal definition of treatment resistance in Lupus Nephritis. Controlled trials in refractory Lupus Nephritis are largely unavailable. Open-labeled studies have reported success of newer immunosuppressive drugs, immunomodulatory therapies, and the biological agents such as mycophenolate mofetil (MMF), calcineurin inhibitors, leflunomide, intravenous immunoglobulin, immunoadsorption, and rituximab in the treatment of cyclophosphamide (CYC) resistant proliferative Lupus Nephritis. More aggressive CYC regimens have been used in Lupus Nephritis, but at the expense of more toxicities. For membranous Lupus Nephritis (MLN), a combination of corticosteroids with either azathioprine, chlorambucil, cyclosporin A, MMF, or CYC is initially effective in two-thirds of patients. More aggressive and costly regimens should be reserved for truly refractory disease with persistent nephrotic syndrome or declining renal function. Evidence regarding the efficacy of MMF in refractory MLN is conflicting and controlled trials are necessary to resolve the controversy. Conclusions The treatment of refractory Lupus Nephritis remains anecdotal. An international consensus in the renal response criteria should be developed and validated so that controlled trials can be performed to compare the efficacy of various treatment modalities.
-
Treatment for Lupus Nephritis: A revisit
Nephrology (Carlton Vic.), 2005Co-Authors: Kar Neng Lai, Sydney C.w. Tang, Chi Chiu MokAbstract:The optimal treatment of severe Lupus Nephritis remains unclear. Regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective. Infection and gonadal toxicity is a major concern of CYC use in patients of reproductive age. In addition, failure to respond or refractory to CYC treatment may lead to the development of end-stage renal disease. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that selectively inhibits activated lymphocytes and renal mesangial cells. Data from experimental Lupus Nephritis and controlled studies, albeit small and lacking statistical power, have revealed that MMF is as effective in Lupus patients as CYC in the induction of renal remission or as maintenance therapy to reduce renal flare in the short term. The significantly less ovarian toxicity and infection when compared to CYC are particularly attractive for the consideration of MMF in Lupus Nephritis. The potential of other new therapeutic agents is discussed together with the need for patient recruitment in future trials of Lupus Nephritis to address the importance of ethnicity as well as histological grading.
Tak Mao Chan - One of the best experts on this subject based on the ideXlab platform.
-
Treatment of severe Lupus Nephritis: the new horizon
Nature reviews. Nephrology, 2014Co-Authors: Tak Mao ChanAbstract:Lupus Nephritis is a common and severe manifestation of systemic Lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, Lupus Nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for Lupus Nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of Lupus Nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with Lupus Nephritis.
-
Lupus Nephritis induction therapy in severe Lupus Nephritis should mmf be considered the drug of choice
Clinical Journal of The American Society of Nephrology, 2013Co-Authors: Brad H. Rovin, Tak Mao Chan, Samir Parikh, Lee A Hebert, C C Mok, Ellen M Ginzler, Lai Seong Hooi, Paul G Brunetta, Romeo Maciuca, Neil SolomonsAbstract:Summary Severe Lupus Nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe Lupus Nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe Lupus Nephritis. We performed a systematic review of the outcomes of treating severe Lupus Nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe Lupus Nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe Lupus Nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolatemofetilandcyclophosphamideareaboutequalininducingremission.However,long-termoutcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe Lupus Nephritis. Clin J Am Soc Nephrol 8: ccc–ccc, 2013. doi: 10.2215/CJN.03290412
-
Lupus Nephritis—An Enriching Opus
Hong Kong Journal of Nephrology, 2009Co-Authors: Tak Mao ChanAbstract:There has been a continuing quest for better treatments for Lupus Nephritis over the past few decades. Against the backdrop of a veritable clinical exigency, our group has sought to refine existing treatments and to establish new therapies that can improve patient outcomes. Our original research on mycophenolate mofetil, which demonstrated its efficacy and tolerability, has led to a change in the treatment paradigm for proliferative Lupus Nephritis. This article reviews our clinical research studies in the different types of Lupus Nephritis.
