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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ELupus nephritis (LN) is a serious complication of systemic lupus erythematosus. This article discusses best practices in the diagnosis and management of patients with LN, as well as the use of oral steroids for the treatment of this disease.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELupus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELupus\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003ELupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). Michelle Petri, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, presented advice on how to diagnose and manage patients with LN. In Dr Petri\u0027s research program, LN is more common and more severe in men. To detect LN, it is often helpful to perform serological testing. Anti-C1q in combination with anti-double-stranded DNA antibodies and low complement levels has the strongest serological association with renal involvement [Orbai AM et al. \u003Cem\u003ELupus\u003C\/em\u003E. 2014].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EHowever, the gold standard for measuring renal disease activity remains kidney biopsy (using the International Society of Nephrology [ISN] class I-VI, and the US National Institutes of Health [NIH] activity index and chronicity index). To assess renal activity clinically, the Systemic Lupus International Collaborating Clinics renal activity score is helpful. The score, derived from a regression analysis using the physician\u0027s rating of renal activity, is top-heavy on proteinuria data.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ETo detect LN, the gold standard is the 24-hour urine protein-to-creatinine ratio (UPCR) [Christopher-Stine L et al. \u003Cem\u003EJ Rheumatol\u003C\/em\u003E. 2004]. Spot UPCRs are acceptable in clinical practice.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EOnce LN is detected, blood pressure (BP) control is key. A systolic BP goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion \u0026gt; 1.0 g\/d [Jafar JH et al. \u003Cem\u003EAnn Intern Med.\u003C\/em\u003E 2003]. Systolic BP \u0026lt; 110 mm Hg may be associated with a higher risk for kidney disease progression (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Systolic Blood Pressure and Its Treatment in Chronic Kidney Disease\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-902246152\u0022 data-figure-caption=\u0022Effect of Systolic Blood Pressure and Its Treatment in Chronic Kidney Disease\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15620\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EEffect of Systolic Blood Pressure and Its Treatment in Chronic Kidney Disease\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EACEI, angiotensin-converting enzyme inhibitor; BP, blood pressure; RCT, randomized clinical trial.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003ESource: Jafar JH et al. \u003Cem\u003EAnn Intern Med.\u003C\/em\u003E 2003.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from Michelle Petri, MD, MPH.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EBP lowering in patients with LN can be achieved effectively with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) [Pohl MA et al. \u003Cem\u003EJ Am Soc Nephrol\u003C\/em\u003E. 2005]. ACEIs and ARBs not only can be used to lower BP but also may function as renal-protective agents [Dur\u00e0n-Barrag\u00e0n S et al. \u003Cem\u003ERheumatology (Oxford)\u003C\/em\u003E. 2008; Perna A et al. \u003Cem\u003EKidney Int.\u003C\/em\u003E 2000]. Patients with LN also should be treated with hydroxychloroquine (HCQ), Dr Petri said, because one study shows that it improves complete response rates with mycophenolate mofetil (MMF) [Kasitanon N et al. \u003Cem\u003ELupus\u003C\/em\u003E. 2006]. Although HCQ is frequently stopped in patients with LN, this study suggests it should be maintained.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EIncreasing 25-hydroxyvitamin D improves UPCR and the Physician\u0027s Global Assessment (PGA) score [Petri M et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E. 2013]. Following vitamin D treatment, there was a 13% decrease in the odds of having a PGA score \u2265 1, a 21% decrease in the odds of having a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score \u2265 5, and a 15% decrease in the odds of having a UPCR \u0026gt; 0.5.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ESLEDAI and visual analog scale renal activity scores worsen during pregnancy. Mycophenolate, though, cannot be used in pregnancy because it causes fetal malformations. The recommendation is to continue prednisone and other treatments to management SLE flares during pregnancy but to never use MMF.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EEthnicity may affect MMF and intravenous (IV) cyclophosphamide treatment response. For example, black and Hispanic patients respond better to MMF than IV cyclophosphamide [Isenberg D et al. \u003Cem\u003ERheumatology\u003C\/em\u003E. 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EThe ALMS maintenance trial [Dooley MA et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2011] showed MMF was significantly superior to azathioprine for maintaining a renal response and in preventing relapse in patients with LN who had a response to induction therapy (\u003Cem\u003EP\u003C\/em\u003E = .003).\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EDr Petri suggests that for the best response, the MMF dosing should be split, the dose should be adjusted for different ethnic groups, and the trough levels should be monitored. A recommended starting dose for MMF is 1000 mg BID. In the future, Dr Petri anticipates the use of multitarget therapies, adding biologics or a calcineurin inhibitor to MMF, tracking disease activity without renal biopsies, and new therapies to reduce renal fibrosis.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003ELiz Lightstone, MD, PhD, Imperial College London, London, United Kingdom, presented on her belief that oral steroid use could be replaced by rituximab for treating LN.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EIn the LUNAR trial [Rovin BH et al. \u003Cem\u003EArthritis Rheum\u003C\/em\u003E. 2012], rituximab plus MMF plus steroids was not superior to MMF plus steroids compared with the proportion of patients with LN who achieved a complete or partial response at week 52. A significant difference favoring rituximab was seen for some of the secondary end points such as a \u2265 50% reduction in proteinuria (\u003Cem\u003EP\u003C\/em\u003E = .04) and complete-response or partial-response proteinuria (\u003Cem\u003EP\u003C\/em\u003E = .04).\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003ELong-term steroid use is problematic because it is associated with significant morbidity and premature mortality [Petri M. \u003Cem\u003ELupus\u003C\/em\u003E. 2000]. Recent studies have supported the use of lower doses of steroids being associated with improved or similar efficacy with fewer side effects. For instance, the Lupus group from Bilbao has shown that a combination of rapidly tapered oral prednisone, methylprednisolone (MP) pulses, and MMF or cyclophosphamide, always with HCQ, is more effective in achieving remission of LN than historical regimens containing high-dose prednisone (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Ruiz-Irastorza G et al. \u003Cem\u003EAutoimmun Rev.\u003C\/em\u003E 2014]. There was less toxicity, better response, and fewer adverse events (AEs) with less steroid use.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Low-Dose Steroids Produce Better Response and Fewer Adverse Events\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-902246152\u0022 data-figure-caption=\u0022Low-Dose Steroids Produce Better Response and Fewer Adverse Events\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/24\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15621\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-16\u0022 class=\u0022first-child\u0022\u003ELow-Dose Steroids Produce Better Response and Fewer Adverse Events\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003ECPC, Cruces protocol cohort; HC, historic cohort.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003EAdapted from Ruiz-Irastorza G et al. Prednisone in lupus nephritis: How much is enough? \u003Cem\u003EAutoimmun Rev.\u003C\/em\u003E 2014;13:206\u2013214. Copyright (2014), with permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EThere is also evidence from renal transplant medicine that adding a biologic is safe, effective, and steroid sparing [Borrows R et al. \u003Cem\u003EAm J Transplant\u003C\/em\u003E. 2004], although in transplantation the biologics have predominantly focused on anti-T cell effects. In LN, there are a lot of registry and case series data to support the use of rituximab in refractory LN. In one report, a complete or partial therapeutic response in predominantly refractory LN was achieved with rituximab in 67% of patients at 12 months [D\u00edaz-Lagares C. \u003Cem\u003EAutoimmun Rev.\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EDr Lightstone and her colleagues have gone a step further and developed the steroid-avoiding Rituxilup protocol. The initial results of a prospective cohort treated with rituximab, MP, and MMF but no oral steroids and followed for at least 1 year were published in 2013 [Condon MB et al. \u003Cem\u003EAnn Rheum Dis.\u003C\/em\u003E 2013]. The regimen was used to treat biopsy-proven active ISN\/Renal Pathology Society (RPS) class III, IV, or V LN, and it showed that oral steroids can be safely avoided when treating LN with Rituxilup. The Rituxilup regimen led to remission, preservation of renal function, and minimal oral steroid use in the majority of the 50 patients.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EIn the first 50 consecutive patients treated with 2 doses of rituximab (1 g) and MP (500 mg) with maintenance treatment with MMF alone, 90% of patients achieved complete biochemical remission (CR) or partial remission (PR) by a median time of 37 weeks (range, 4\u2013200). By 52 weeks, CR and PR had been achieved in 52% (n = 26) and 34% (n = 17), respectively.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EIn a 5-year follow-up analysis from this study that included 42 patients, the majority (88%) achieved CR or PR. Median time to remission was 9 months with 77% never requiring oral steroids. AEs were similar to those in the initial study. The majority had preserved renal function.\u003C\/p\u003E\n         \u003Cp id=\u0022p-21\u0022\u003ETo conclude, Dr Lightstone stated that predictors of poor outcomes in the Rituxilup cohort were baseline creatinine \u0026gt; 120 \u03bcmol\/L and a \u0026lt; 50% reduction in proteinuria at 6 months. In addition, the minimal use of oral steroids in the majority would be expected to have long-term benefits in terms of cardiovascular disease risk and reduced side effects. The Rituxilup regimen will now be evaluated formally in a phase 3, open-label, multicenter, international, randomized controlled trial where the Rituxilup regimen will be compared with MMF and oral steroids [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01773616\u0026amp;atom=%2Fspmdc%2F14%2F51%2F24.atom\u0022\u003ENCT01773616\u003C\/a\u003E].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/51\/24.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzlv6q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzlv6q\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}