Abstract:
:Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naïve adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Rondeau E,Scully M,Ariceta G,Barbour T,Cataland S,Heyne N,Miyakawa Y,Ortiz S,Swenson E,Vallee M,Yoon SS,Kavanagh D,Haller H,311 Study Group.doi
10.1016/j.kint.2020.01.035subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1287-1296issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(20)30152-6journal_volume
97pub_type
杂志文章abstract::The role of immunoglobulin (Ig) Fc-macrophage cell surface receptor affinity (macrophage Fc-affinity) in determining the mediation systems responsible for immune glomerular injury has been studied. Glomerular injury was initiated in rabbits by the passive administration of immunoglobulin preparations directed against ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.228
更新日期:1989-10-01 00:00:00
abstract::Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.03.012
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00203.x
更新日期:2000-08-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2019.02.009
更新日期:2019-08-01 00:00:00
abstract::Tissandié and colleagues report in this issue on their studies of IgA1 glycosylation and biological activities of IgA1-containing circulating immune complexes in patients with alcoholic cirrhosis who developed secondary renal disease with IgA deposits, secondary IgA nephropathy. Their seminal findings demonstrate abno...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.302
更新日期:2011-12-01 00:00:00
abstract::Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 pro...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001630
更新日期:2006-08-01 00:00:00
abstract::Leptin is an adipocyte-derived hormone that acts as a major regulator of food intake and energy homeostasis. It circulates both as a free and as a protein-bound entity. Leptin is released into the blood in proportion to the amount of body fat and exerts sustained inhibitory effects on food intake while increasing ener...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000182
更新日期:2006-03-01 00:00:00
abstract::The beta-amino acid transport capabilities of rat renal epithelium were assessed using brushborder membrane vesicles (BBMV). Taurine, a metabolically inert sulfur-containing amino acid, was studied with emphasis on the renal adaptation to dietary sulfur amino acid alteration. Three isoproteinic diets were given to Spr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.198
更新日期:1983-11-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00245.x
更新日期:2005-04-01 00:00:00
abstract::The remnant kidney (RK) exhibits an enhanced fractional excretion of phosphate (FEPi) even in the absence of parathyroid hormone (PTH). Thus, factors other than PTH contribute to this adaptive phosphaturia. Dopamine (DA) infusion is phosphaturic, whereas stimulation of adrenoreceptors is antiphosphaturic. Therefore, t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.144
更新日期:1993-05-01 00:00:00
abstract::The family of bone morphogenetic proteins. Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-beta (TGF-beta) superfamily of growth factors. The first BMPs were originally identified by their ability to induce ectopic bone formation when implanted under the ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2000.00081.x
更新日期:2000-06-01 00:00:00
abstract::Insulin-like growth factor I (IGF-I) has been found in the kidney, particularly in the collecting duct in the rat. Since cultured rabbit collecting duct cells constitute a convenient system for in vitro studies, we have examined whether these cells secrete IGF-I. Culture medium conditioned by collecting duct cells was...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.3
更新日期:1991-01-01 00:00:00
abstract::Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Dep...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.42
更新日期:2011-06-01 00:00:00
abstract::Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney sensitive to necroptosis mediated by a second dose. Unresolved injury and sustained necrosis, therefore, may represent a pathophysiological means of tra...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.12.004
更新日期:2019-04-01 00:00:00
abstract::From September 9 to October 3, 1994, five patients on maintenance hemodialysis in a dialysis unit in Tokyo contracted hepatitis B virus (HBV) infection successively, and four of them died of fulminant hepatitis. The unit treated 181 patients three times a week on eight shifts, and all five afflicted patients were on t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.499
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:Determinants of inter-individual variation in blood pressure (BP) response to antihypertensive therapy remain largely unknown. Although differences in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have been associated with variation in blood pressure response to hydrochlorothiazid...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00200.x
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00440.x
更新日期:2000-12-01 00:00:00
abstract::Diagnosis and treatment of atherosclerotic renal artery stenosis (ARAS) in the elderly is a never-ending challenge for every nephrologist. Kalra et al. report that adjusted hazard ratios for ARAS increased threefold from 1992 to 2004 in 16 million United States Renal Data System participants aged 66 years or older. Ho...
journal_title:Kidney international
pub_type: 信件
doi:10.1038/ki.2009.326
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:To chart the epidemiology of primary glomerular disease by means of a prospective regional study in the southern part of The Netherlands. METHODS:Experienced renal technicians collected renal biopsies, blood, and 24-hour urine samples at the bed site in each of the participating hospitals. The material was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00835.x
更新日期:2004-09-01 00:00:00
abstract::Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.168
更新日期:2009-09-01 00:00:00
abstract::To date direct evidence for the presence of a H-K-ATPase in the medulla comes from proton and potassium transport studies performed on K-restricted animals and K dependent ATP hydrolysis and Rb uptake in both normal and K-depleted animals. The present work examines K-dependent acidification in the medulla of rabbits o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.392
更新日期:1992-11-01 00:00:00
abstract::Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman's capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.528
更新日期:2009-01-01 00:00:00
abstract::beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.368
更新日期:1992-10-01 00:00:00
abstract::The role of peritoneal dialysis (PD) in renal replacement therapy (RRT) remains unclear. There are no controlled trials to provide hard evidence of its efficacy. Comparative studies with haemodialysis from different centres and countries have given conflicting results even when allowing for case mix. Data from the Uni...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.1998.00183.x
更新日期:1998-12-01 00:00:00
abstract::On a typical Western diet, the body is faced with the generation of a metabolically derived acid load that must be excreted to maintain systemic acid-base balance. The kidney is responsible for this task and matches daily acid excretion with daily acid production. Multiple nephron segments are involved in the process,...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002543
更新日期:2007-12-01 00:00:00
abstract::The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a s...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.118
更新日期:2011-08-01 00:00:00
abstract::Membranous nephropathy is characterized by deposition of immune complexes along the glomerular basement membrane. PLA2R and THSD7A are target antigens in 70% and 1-5% of primary membranous nephropathy cases, respectively. In the remaining cases, the target antigen is unknown. Here, laser microdissection of glomeruli f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.014
更新日期:2020-01-01 00:00:00
abstract::Tenascin-C is an extracellular matrix glycoprotein that plays a critical role in kidney fibrosis by orchestrating a fibrogenic niche. Here, we demonstrate that tenascin-C is a biomarker and a mediator of kidney fibrogenesis by impairing tubular integrity. Tenascin-C was found to be increased in kidney biopsies from pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.026
更新日期:2020-05-01 00:00:00
abstract::Elevated serum levels of uric acid consistently correlate with hypertension, but the directionality of the association remains debated. To help define this relationship, we used a controlled setting within a homogeneous Amish community and the Mendelian randomization of a nonsynonymous coding single-nucleotide polymor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.414
更新日期:2012-03-01 00:00:00