The treatment of lupus nephritis.
Ontology highlight
ABSTRACT:
SUBMITTER: D'Cruz DP
PROVIDER: S-EPMC549098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus. In this review, we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis.Localized long-lived plasma cells have been identified as playing an important role in lupus nephritis. In addition, the roles of aberrant expression of microRNAs and proinflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none has been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of lupus nephritis are being studied, including belimumab which was recently approved for nonrenal systemic lupus erythematosus. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of lupus nephritis.Lupus nephritis is a potentially devastating complication of systemic lupus erythematosus. Immune cells, cytokines, and epigenetic factors have all been recently implicated in lupus nephritis pathogenesis. These recent discoveries may enable a paradigm shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific pathogenic mediators at specific points in time in the progression of disease.
| S-EPMC4221732 | biostudies-literature
Project description:ObjectiveIn light of reports of de novo LN during belimumab (BLM) treatment, we sought to determine its frequency and contributing or protective factors in a real-life setting.MethodsPatients with SLE who received BLM between 2011 and 2017 at five European academic practices were enrolled (n = 95) and followed longitudinally for a median time of 13.1 months [interquartile range (IQR): 6.0-34.7]; 52.6% were anti-dsDNA positive, 60.0% had low complement levels, and 69.5% had no renal involvement prior to/at BLM initiation [mean disease duration at baseline: 11.4 (9.3) years]. Age- and sex-matched patients with non-renal SLE who had similar serological profiles, but were not exposed to BLM, served as controls (median follow-up: 132.0 months; IQR: 98.3-151.2).ResultsWe observed 6/66 cases (9.1%) of biopsy-proven de novo LN (4/6 proliferative) among the non-renal BLM-treated SLE cases after a follow-up of 7.4 months (IQR: 2.7-22.2). Among controls, 2/66 cases (3.0%) of de novo LN (both proliferative) were observed after 21 and 50 months. BLM treatment was associated with an increased frequency and/or shorter time to de novo LN [hazard ratio (HR): 10.7; 95% CI: 1.7, 67.9; P = 0.012], while concomitant use of antimalarial agents along with BLM showed an opposing association (HR: 0.2; 95% CI: 0.03, 0.97; P = 0.046).ConclusionAddition of BLM to standard-of-care did not prevent LN in patients with active non-renal SLE, but a favourable effect of concomitant use of antimalarials was implicated. Studies of whether effects of B-cell activating factor inhibition on lymphocyte subsets contribute to LN susceptibility are warranted.
| S-EPMC8409994 | biostudies-literature
Project description:Our previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2-3 mg/d; mycophenolate mofetil, 0.50-0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.
| S-EPMC5698076 | biostudies-literature
Project description:Despite recent developments and treatment successes, the outcome, and prognosis of patients with lupus nephritis (LuN) have not greatly changed since the 1980s. This review covers the application of new concepts to the understanding of renal inflammation and the study of new pharmacologic agents to improve patient outcomes.Studies have shown that the presence of anti-vimentin antibodies and T follicular helper cells in patient biopsies is associated with more severe interstitial inflammation, which has been tied to faster disease progression and onset of end-stage renal disease. Additionally, data regarding the role of serum IgE antidouble-stranded DNA antibodies in LuN by means of mediating IFN1 production by plasmacytoid dendritic cells are highlighted. Finally, a thorough review of completed and currently open clinical trials of therapeutic agents is provided.Current management of LuN is guided almost exclusively by glomerular involvement. Based on the data provided in this review, we argue that renal tubulointerstitial inflammation is no less important and represents an overlooked feature in the current clinical approach to patients. Tubulointerstitial inflammation is driven by both adaptive and innate immune mechanisms that are still poorly understood. Studying these pathogenic processes promises to reveal new therapeutic opportunities for those LuN patients with the worst prognosis.Alternate video abstract introduction (see Video, Supplemental Digital Content 1, with introduction by two of the authors - VL and KT). Abstract Video: http://links.lww.com/COR/A35.
| S-EPMC4965286 | biostudies-literature
Project description:Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
| S-EPMC2678035 | biostudies-literature
Project description:The constant updating of lupus drug treatment guidelines has led to a question. How can the efficacy of treatment be more effectively monitored? Systemic lupus erythematosus (SLE) is a complex autoimmune disease that often presents clinically with multi-organ involvement, and approximately 30% of patients with SLE develop lupus nephritis (LN). Therefore, it is important to better track disease progression and drug efficacy. Now, kidney biopsy is still the gold standard for diagnosing and guiding the treatment of LN, but it is invasive and expensive. If simple, non-invasive and effective biomarkers can be found, drug intervention and prognosis can be better monitored and targeted. In this review, we focus on LN and explore biomarkers related to LN therapeutics, providing clinicians with more possibilities to track the therapeutic effect of drugs, improve treatment options and assess patient outcomes.
| S-EPMC10669579 | biostudies-literature
Project description:Lupus nephritis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. The general consensus is that 60% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The present review summarizes our current understanding of the pathogenic mechanisms underlying lupus nephritis and how the disease is currently diagnosed and treated.
| S-EPMC3308062 | biostudies-literature
Project description: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.
| S-EPMC5477208 | biostudies-literature
Project description:Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials.
| S-EPMC7916202 | biostudies-literature
Project description:Background: Lupus nephritis (LN) is the most common secondary glomerular diseases that will cause end-stage renal disease (ESRD) and renal-related death. The cost-effectiveness of various treatments for LN recommended by official guidelines has not been investigated in China. Our study is to evaluate clinical prognosis and cost-effectiveness of the current treatments for severe LN. Methods: A Markov model was simulated for 1,000 LN patients of 30 years old, over a 3-years and 30-years lifetime horizon respectively. We assessed the cost-effectiveness of six therapeutic strategies from a societal perspective, with cyclophosphamide (CYC) or mycophenolate mofetil (MMF) induction therapy followed by CYC, MMF or azathioprine (AZA) maintenance therapy. Main outcomes included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER) and clinical prognosis. One and three times gross domestic product (GDP) per capita were used as the willingness-to-pay (WTP) thresholds. We also carried out sensitivity analysis under a lifetime horizon. Results: Compared with the baseline strategy of CYC induction and maintenance, for a 3-years horizon the most cost-effective strategy was CYC induction and AZA maintenance with $448 per QALY gained, followed by MMF induction and AZA maintenance which however was not cost-effective under the one times GDP per capita WTP threshold. For a lifetime horizon, CYC induction and AZA maintenance remained the most cost-effective strategy but MMF induction and maintenance became cost-effective under the one times GDP per capita WTP threshold and achieved a higher complete remission rate (57.2 versus 48.9%) and lower risks of ESRD (3.3 versus 5.8%) and all-cause mortality (36.0 versus 40.8%). The risk of developing ESRD during maintenance was the most influential parameter affecting ICER. Conclusions: The strategy of CYC induction followed by AZA maintenance was the most cost-effective strategy in China for short-term treatment, while the strategy of MMF in both induction and maintenance became cost-effective and yielded more desirable clinical outcomes for lifetime treatment. The uncertainty analysis supported the need for monitoring the progression to ESRD.
| S-EPMC8450585 | biostudies-literature