{"title":"Nephrogenic systemic fibrosis symptoms alleviated by renal transplantation","authors":"Nannie Bangsgaard MD, Jesper Melchior Hansen MD, PhD, DMSc, Peter Marckmann MD, DMSc, Lone Skov MD, PhD, DMSc","doi":"10.1002/dat.20507","DOIUrl":"10.1002/dat.20507","url":null,"abstract":"<p>Nephrogenic systemic fibrosis (NSF) is a rare, serious, and life-threatening disease of patients with severe renal impairment. Gadolinium-containing contrast agents have been shown to be the crucial trigger. There is no proven medical cure for the disease, and symptomatic treatment options are limited. Anecdotal reports have shown partial or complete resolution of NSF following successful renal transplantation early in the course of NSF. In this report, we describe alleviation of NSF symptoms in two women following successful renal transplantation more than 3 years after onset of NSF. Dial. Transplant.</p>","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 2","pages":"86-87"},"PeriodicalIF":0.0,"publicationDate":"2011-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dat.20507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51496772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rx Report†","authors":"","doi":"10.1002/dat.20540","DOIUrl":"https://doi.org/10.1002/dat.20540","url":null,"abstract":"<p>A new injectable antibiotic, ceftaroline fosamil (Teflaro), has been approved by the United States (U.S.) Food and Drug Administration (FDA) to treat adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).<span>1</span> A dosage adjustment is necessary in patients with moderately impaired renal function (CrCl 30 mL/min to < 50 mL/min) or severely impaired renal function (CrCl < 30 mL/min).<span>2</span> The most common side effects in trials were diarrhea, nausea, and rash.</p><p>Daptomycin for injection (Cubicin) was recently FDA-approved as a oncedaily two-minute intravenous (IV) injection.<span>3</span> Previously it was approved as a 30-minute infusion for treating MRSA-complicated skin infections and bacteremia.</p><p>Atrasentan (Xinlay), a highly selective endothelin-A receptor antagonist (SERA), which antagonizes the effect of endothelin-l (ET-l), led to reductions in residual albuminuria in diabetic nephropathy patients when added to angiotensin receptor blocker or angiotensin-converting-enzyme inhibitor therapy.<span>4</span> The middle atrasentan dose reduced the urine albumin-to-creatinine (UACR) ratio by 42% compared with reductions of 34% and 21% with the highest and lowest doses, respectively.<span>5</span> Half the patients who received the middle dose also realized a >40% reduction in UACR from baseline versus 17% for placebo-treated patients.</p><p>Bardoxolone, a first-in-class antioxidant inflammation modulator for treating chronic kidney disease (CKD), was shown in mid-stage clinical trials to significantly improve renal function in patients with CKD and type 2 diabetes mellitus (T2DM).<span>6</span> Phase 3 clinical trials are expected to be started soon.</p><p>A complete response letter related to the potential approval of exenatide extended-release for injectable suspension (Bydureon), was received by its manufacturer on October 19, 2010.<span>7</span> The FDA has requested that exenatide extended-release undergo a comprehensive QT study at higher dose exposure levels to determine the effect of the drug on patient heart rate.<span>8</span> The dose to be studied will be supratherapeutic. Additional efficacy data from studies already conducted were also requested by the FDA. It is anticipated that the response to the FDA letter will be completed by the end of 2011. It is intended for once-weekly injection.</p><p>Ferric citrate (Zerenex) is currently in Phase 3 clinical trials to treat hyperphosphatemia in end-stage renal disease (ESRD) patients on dialysis.<span>9</span> The strength of this oral formulation is 1 gram. Patients who received 6 grams of ferric citrate daily had a decrease in serum phosphorous levels of 25% after 28 days, those who took 8 grams had a 29% drop in 28 days, and those who took 1 gram daily showed no serum phosphorous reduction. A 58-week study is ongoing","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 2","pages":"89-90"},"PeriodicalIF":0.0,"publicationDate":"2011-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dat.20540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137685846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A community at home†","authors":"Brian Riddle","doi":"10.1002/dat.20541","DOIUrl":"10.1002/dat.20541","url":null,"abstract":"<p>When I was 22 months old, I was diagnosed with cystinosis. My parents knew the day would come when I would need renal-replacement therapy, and researched my options. After my kidneys failed when I was 10 years old, I received a transplant from a cadaver, but it was rejected after six months. A few months later, my mother donated one of her kidneys. It lasted four wonderful years before rejection. I then received a kidney from my father, which lasted only 13 months. Between each transplant, I would undergo in-center hemodialysis (HD). I often felt exhausted and depressed. When the last kidney failed during my high school years, I decided to seek at-home therapy through peritoneal dialysis (PD).</p><p>PD was a successful treatment for me for more than 12 years. It wasn't always easy, but I graduated from high school on time with honors, went on to college to study at the University of Pittsburgh, and got a fulltime job with a major insurance company. I later developed encapsulated peritoneal sclerosis (EPS), a rare condition associated with long-term peritoneal dialysis use that causes fibrotic changes of the peritoneal membrane and ultrafiltration failure, making my continued PD therapy impossible.</p><p>When I returned to in-center HD in 2006, I was very sick from living with my kidney disease and other health conditions. I weighed just 86 pounds, and it was hard to put on weight with the EPS and the restrictive diet I needed to follow as an in-center HD patient. That same year, my nephrologist informed me about another option—the NxStage System One, which would allow me to dialyze at home with a trained partner using a machine about the size of a portable TV. Additionally, the system would allow me to undergo more-frequent dialysis, better resembling natural kidney function and providing more clinical benefits. I trained to dialyze at home as soon as I could with my mother as my care partner.</p><p>Almost immediately, I started to feel better. I was able to eliminate all blood pressure medications and could eat more to gain weight. Traveling and other day-to-day activities became easier, and I now had more control of my life.</p><p>In 2007, I became involved with an online group comprised of 20 to 30 people discussing home dialysis. With my new found health and quality of life, I wanted to learn more and share my experiences with others in the group. I became acquainted with the group creator, Rich Berkowitz, a fellow NxStage HD patient. Rich conceived the idea of formalizing the group, and I teamed with him to became a group moderator. Eventually, we created the website now known as NxStageUsers (the group is independent of NxStage Medical and all dialysis cen-ters). More people joined the group every day, and eventually we wanted to expand the group's goals.</p><p>Our aim was to support fellow dia-lyzors and prospective ones, share our personal experiences, and post current events and the latest news on dialysis and Centers for Medicare and","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 2","pages":"92"},"PeriodicalIF":0.0,"publicationDate":"2011-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dat.20541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51498600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The D&T Report","authors":"","doi":"10.1002/dat.20543","DOIUrl":"https://doi.org/10.1002/dat.20543","url":null,"abstract":"<p>The disparity in the burden and outcomes of chronic kidney disease (CKD) between whites and racial and ethnicminorities in the United States is well documented.<span>1</span> There are several factors that may contribute to this discrepancy among specific groups. Blacks and Hispanics have genetic predispositions toward hypertension and diabetes, respectively. These populations as a whole, when compared with whites, are often comprised of a higher number of low-income families, more isolated or impoverished neighborhoods, and they often have less education and poorer access to healthcare. As a result, there are nearly 33% more minorities who receive renal replacement therapy than there are whites.<span>2</span></p><p>Socioeconomic status may be even more important than racial or ethnic factors. In an analysis of data from the National Health and Nutrition Examination Survey, Rajnish Mehrotra, MD, a nephrologist and professor of medicine at the University of California, LosAngeles School of Medicine, and colleagues found that black and Hispanic patients with endstage renal disease (ESRD) who were younger than 65 had a significantly higher risk of mortality than their white counterparts. However, the difference became insignificant when the authors adjusted their calculations for socioeconomic and access- to-care variables.<span>3</span> “What this tells me is that the higher risk for death [among black and Hispanic patients] is related to issues that can be summarized in terms of socioeconomic characteristics,” says Dr. Mehrotra. In other words, a large part of the difference relates to sociology rather than biology, he says.</p><p>Poverty may take a greater toll on blacks than on whites. Deidra Crews, MD, a nephrologist and associate professor of medicine at Johns Hopkins School of Medicine in Baltimore, and colleagues found that the prevalence of CKD was 27% higher among Baltimore residents with family incomes below the federal poverty level, as compared with those above it. However, blacks living below the poverty level were 33% more likely to have CKD than whites of similar income. <span>4</span> “Poverty may have a different impact on black than white patients in determining who's at risk for CKD,” says Dr. Crews. “One possible explanation is that, in an urban setting like ours, there may be some factors that affect blacks differentially over whites.”</p><p>In another study from Johns Hopkins, senior author L. Ebony Boulware, MD, MPH, and colleagues at the university's School of Public Health examined racial differences in sources of healthcare, health insurance, and incidence of CKD in 3,883 white and 1,607 black participants. The black patients were significantly less likely to have access to healthcare, and significantly more likely to have CKD. Adjustment for demographic, socioeconomic, lifestyle, and clinical factors accounted for 64% of that increased risk, and limited access to healthcare accounted for an additional 10%. Their conclu","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 2","pages":"54-58"},"PeriodicalIF":0.0,"publicationDate":"2011-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dat.20543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137685845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New and emerging treatments for lupus nephritis","authors":"Pietro A.A. Canetta MD, Gerald B. Appel MD","doi":"10.1002/dat.20514","DOIUrl":"10.1002/dat.20514","url":null,"abstract":"<p>The last decade has witnessed con-siderable progress in the thera-peutic approach to systemic lupus erythematosus (SLE), and particu-larly its renal manifestations. Advances in understanding the immunological basis of SLE, the development of increasingly specific and better tolerated pharmacologic agents, and an increased emphasis on rigor-ous clinical trial design have combined to produce validated treatment regimens with greater efficacy and less toxicity compared with the past.<span>1</span></p><p>Despite these advances, there remains room for continued improvement. Lupus nephritis continues to carry substantial morbidity and mortality, affecting patients mostly in the prime of their youth.<span>2</span>, <span>3</span> Even with aggressive regimens, treatment-refrac-tory lupus nephritis may occur in a significant proportion of patients,<span>4</span>, <span>5</span> and disease relapses are both common and associated with worse prognosis.<span>6-8</span> For these reasons, a large number of novel therapies are pres-ently in various stages of development and promise to provide further options for the treating physician. In this article, we sum-marize current therapeutic standards of care and review novel and emerging treatments for lupus nephritis.</p><p>While SLE may have a variety of presen-tations in the kidney, glomerulonephritis remains the most common and the most well studied.<span>9</span> The International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of lupus nephritis provides a standardized, repro-ducible classification of disease that has essentially replaced the older World Health Organization classification.<span>10</span> At present, the histologic pattern of disease as classified by ISN/RPS broadly determines the therapeutic approach, placed in the appro-priate context of an individual patient's clinical parameters.</p><p>In the setting of mild disease, repre-sented by ISN/RPS class I nephritis (nor-mal glomeruli by light microscopy with mesangial deposits on immunofluorescence or electron microscopy) and the majority of class II nephritis (pure mesangial hyper-cellularity by light microscopy with mesan-gial immune deposits), immunosuppressive treatment is not indicated. Most patients with these forms of disease will have good long-term renal outcomes. The cornerstone of therapy is control of blood pressure and suppression of proteinuria through block-ade of the renin-angiotensin-aldosterone system (RAAS) with either an angioten-sin-converting enzyme inhibitor (CEI) or angiotensin receptor blocker (ARB).</p><p>The rationale for this approach is based on extrapolation from human studies in other chronic proteinuric kidney diseases<span>11</span> as well as an abundance of animal studies.<span>12-14</span> Additional support has been provided by a recent report from the lupus in minorities: nature versus nurture (LUMINA) cohort.<span>15</span> In this cohort, 80 of 378 patients (21%) were CEI users. CEI ","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 2","pages":"67-71"},"PeriodicalIF":0.0,"publicationDate":"2011-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/dat.20514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51497394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The three‐signal hypothesis of lymphocyte activation/targets for immunosuppression","authors":"S. Goral","doi":"10.1002/DAT.20527","DOIUrl":"https://doi.org/10.1002/DAT.20527","url":null,"abstract":"Kidney transplantation is the preferred mode of renal replacement therapy for most patients with end-stage renal disease. Despite the increasing success of transplantation over the years, allograft rejection remains a major problem. Recently, there has been considerable improvement in understanding the role of the immune system in rejection. In the setting of transplantation, T cells have proved to be crucial players in the immune response, and their activation has been shown to be a very tightly regulated process involving numerous interactions of receptors including the T-cell receptor (TCR):CD3 complex, co-stimulatory receptors, and appropriate signaling molecules, resulting in production of cytokines as well as clonal expansion and differentiation of effector T lymphocytes. In this review, current knowledge of the mechanisms of lymphocyte activation as well as potential targets for various immunosuppressive agents are discussed.","PeriodicalId":51012,"journal":{"name":"Dialysis & Transplantation","volume":"40 1","pages":"14-16"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/DAT.20527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51498082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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