单克隆免疫性球蛋白相关性肾病,cfDNA基本知识

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图表来源互连网

基本属性

  • 长度
    澳门新葡8455最新网站 1

    Azad A A, Volik S V, Wyatt A W, et al. Androgen Receptor Gene
    Aberrations in Circulating Cell-Free DNA: Biomarkers of
    Therapeutic Resistance in Castration-Resistant Prostate
    Cancer.[J]. Journal of Urology, 2015, 194(3):704-704.

澳门新葡8455最新网站 2
在167bp左右(对应染色小体长度)有2个峰,并且其余的峰有着十.五bp的周期波动,对应着核小体大旨DNA的螺距

Snyder M W, Kircher M, Hill A J, et al. Cell-free DNA comprises an in
vivo nucleosome footprint that informs its tissues-of-origin[J].
Cell, 2016, 164(1-2):57.

  • 生物学来源
  1. 凋亡和坏死

    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, et
    al. (2001) DNA fragments in the blood plasma of cancer patients:
    quantitations and evidence for their origin from apoptotic and
    necrotic cells Cancer Res 61:1659–65. pmid:11245480
    Giacona M B, Ruben G C, Iczkowski K A, et al. Cell-free DNA in
    human blood plasma: length measurements in patients with
    pancreatic cancer and healthy controls[J]澳门新葡8455最新网站,. Pancreas, 1998,
    17(1):89.

  2. 移植物恐怕胎儿的游离DNA(参考文献见下)

  3. 独立自主激活的DNA的自由

    Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P (2001)
    About the possible origin and mechanism of circulating DNA
    apoptosis and active DNA release. Clin Chim Acta 313:139–42.
    pmid:11694251

  • 应用
  1. 胚胎的DNA会游离到孕妇的血液中,怀男孩的产妇血液可以检验到Y染色体,还可用于产前检验,二一和1八③体

    Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman
    CWG,et al. Presence of fetal DNA in maternal plasma and serum.
    Lancet
    1997;350:485–7
    Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das
    AF,et al. DNA sequencing versus standard prenatal aneuploidy
    screening.N Engl J Med 2014;370:799–808

  2. 器官移植免疫性排斥发生的细胞病逝,DNA会释放到血液中,因而用于器官移植状态的监督检查

    Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U,
    et al.Donor-derived cell-free DNA is a novel universal biomarker
    for allograft rejection in solid organ transplantation. Transplant
    Proc 2015;47:2400–3

  3. cfDNA浓度与外伤、久痢的侵蚀程度有关

    Butt AN, Swaminathan R. Overview of circulating nucleic acids in
    plasma serum. Ann N Y Acad Sci 2008;1137:236–42

  4. 高浓度cfDNA也用于ICU仙逝的前瞻,也可用于预测脓毒症和脓毒性休克,无菌性炎症,心肌梗死和无影象学结果的闭合性脑外伤伤者患病意况。

    Volik S, Alcaide M, Morin R D, et al. Cell-free DNA (cfDNA):
    Clinical Significance and Utility in Cancer Shaped By Emerging
    Technologies[J]. Molecular Cancer Research Mcr, 2016:898-908.

  5. 肿瘤来源的cfDNA,能够窥见肿瘤相关的剧变、杂合子缺点和失误(LOH)、基因扩大与扩展、癌病毒DNA、抑癌基因运维子区的超芳香烃化,由此能够完毕在无创条件下商讨肿瘤DNA

    Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M.
    Neoplastic characteristics of the DNA found in the plasma of
    cancer patients.
    Oncology 1989;46:318–22
    Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et
    al.Microsatellite alterations in plasma DNA of small cell lung
    cancer patients.
    Nat Med 1996;2:1033–5
    Chiang P-W, Beer DG, Wei W-L, Orringer MB, Kurnit DM. Detection
    oferbB-2 amplifications in tumors and sera from esophageal
    carcinoma
    patients. Clin Cancer Res 1999;5:1381–6
    Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong
    V,Lertsanguansinchi P, Yenrudi S, et al. Epstein-Barr viral DNA in
    serum of
    patients with nasopharyngeal carcinoma. Clin Cancer Res
    1998;4:665–9
    Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB,
    HermanJG. Detection of aberrant promoter hypermethylation of tumor
    suppressor
    genes in serum DNA from non-small cell lung cancer patients.
    Cancer Res1999;59:67–70.

  6. 核小体在TSS区是不是占据,影响cfDNA的深度,因而得以用来推论基因的公布情状

    Ulz P, Thallinger G G, Auer M, et al. Inferring expressed genes by
    whole-genome sequencing of plasma DNA.[J]. Nature Genetics,
    2016, 48(10):1273.

AstraZeneca

2、 Nasr SH, Valeri AM, Cornell LD, Fidler
ME,Sethi S, D’Agati
VD, et al.: Renal monoclonalimmunoglobulin deposition disease:
A reportof 64 patients from a single
institution.Clin J Am Soc Nephrol 7: 231–239,
2012.

肿瘤放射治疗组(大切诺基TOG)9804考试同样评估了无放射性治疗时DCIS治疗成效。与ECOG和丹娜法伯的单组试验不一样,该考试病人接受保乳手术(BCS)后随机分入有放射治疗组和无放射治疗组。该考试低危机定义与ECOG试验稍有例外,肿瘤大小≤2.5cm、肿瘤边缘中性(neuter gender)最小距离为三mm、四分之二级DCIS病者。由于收入不强烈,提前终止了试验。但是即使在低风险人群中,放射疗法能强烈降低同侧浸润性月经不调复发率(IBTCR-V)(七年随同访问,有放疗一%
vs
无放射性治疗七%;P<0.00一)。其它,病人对放射性治疗的耐受性卓绝。两组的三级慢性毒性产生率相同(约肆%),放射性治疗组晚期毒性反应发生率<1%。HavalTOG
980四试验回应了ECOG试验结果,低危害病人只要不用放射性治疗每年净增复发风险一%。需求留意的是,这么些研商未有正规使用抗雌激素治疗。抗雌激素治疗比例分别为丹娜法伯试验0%、ECOG试验3/10、智跑TOG
980四考试两组加起来6二%。假如全数的病者都领受抗雌激素治疗,那么援助放射性治疗成效不那么明白。不过固然在从严监测的试验中激素治疗依从性也不高。专门评估内分泌治疗的NSABP
B-3伍试验中病人依从性只有12分之7。

定义

Circulating free DNA or Cell free DNA
(cfDNA):循环游离DNA或许细胞游离DNA,释放到血浆中的降解的DNA片段。

Phase 2

前段时间有战友已对该文举行总论翻译,个人觉得各论部分也杰出值得阅读与收藏,特整理为七个表格,便于翻看。

参考文献
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Nurses Health Study. Cancer. 2005;103:1778-84.
4.Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of
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5.Narod SA, Iqbal J, Giannakeas V, et al. Breast cancer mortality after
a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;1:888-96.
6.Eusebi V, Feudale E, Foschini MP, et al. Long-term follow-up of in
situ carcinoma of the breast. Semin Diagn Pathol. 1994;11:223-35.
7.Wapnir IL, Dignam JJ, Fisher B, et al. Long-term outcomes of invasive
ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and
B-24 randomized clinical trials for DCIS. J Natl Cancer Inst.
2011;103:478-88.
8.Fisher B, Costantino J, Redmond C, et al. Lumpectomy compared with
lumpectomy and radiation therapy for the treatment of intraductal breast
cancer. N Engl J Med. 1993;328:1581-6.
9.Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for
local recurrence after postoperative radiotherapy after sector resection
for ductal carcinoma in situ of the breast. J Clin Oncol.
2008;26:1247-52.
10.Julien JP, Bijker N, Fentiman IS, et al. Radiotherapy in
breast-conserving treatment for ductal carcinoma in situ: first results
of the EORTC randomised phase III trial 10853. EORTC Breast Cancer
Cooperative Group and EORTC Radiotherapy Group. Lancet.
2000;355:528-33.
11.Houghton J, George WD, Cuzick J, et al. Radiotherapy and tamoxifen in
women with completely excised ductal carcinoma in situ of the breast in
the UK, Australia, and New Zealand: randomised controlled trial. Lancet.
2003;362:95-102.
12.Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of
intraductal breast cancer: National Surgical Adjuvant Breast and Bowel
Project B-24 randomised controlled trial. Lancet. 1999;353:1993-2000.
13.Early Breast Cancer Trialists’ Collaborative Group, Correa C, McGale
P, et al. Overview of the randomized trials of radiotherapy in ductal
carcinoma in situ of the breast. J Natl Cancer Inst Monogr.
2010;2010:162-77.
14.Solin LJ, Gray R, Hughes LL, et al. Surgical excision without
radiation for ductal carcinoma in situ of the breast: 12-year results
from the ECOG-ACRIN E5194 study. J Clin Oncol. 2015;33:3938-44.
15.Wong JS, Chen YH, Gadd MA, et al. Eight-year update of a prospective
study of wide excision alone for small low- or intermediate-grade ductal
carcinoma in situ (DCIS). Breast Cancer Res Treat. 2014;143:343-50.
16.McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective
randomized trial for good-risk ductal carcinoma in situ comparing
radiotherapy with observation. J Clin Oncol. 2015;33:709-15.
17.Margolese RG, Cecchini RS, Julian TB, et al. Anastrozole versus
tamoxifen in postmenopausal women with ductal carcinoma in situ
undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised,
double-blind, phase 3 clinical trial. Lancet. 2016;387:849-56.
18.Sagara Y, Freedman RA, Vaz-Luis I, et al. Patient prognostic score
and associations with survival improvement offered by radiotherapy after
breast-conserving surgery for ductal carcinoma in situ: a
population-based longitudinal cohort study. J Clin Oncol.
2016;34:1190-6.
19.Smith GL, Smith BD, Haffty BG. Rationalization and regionalization of
treatment for ductal carcinoma in situ of the breast. Int J Radiat Oncol
Biol Phys. 2006;65:1397-1403.
20.Early Breast Cancer Trialists’ Collaborative Group, Darby S, McGale
P, et al. Effect of radiotherapy after breast- conserving surgery on
10-year recurrence and 15-year breast cancer death: meta-analysis of
individual patient data for 10,801 women in 17 randomised trials.
Lancet. 2011;378:1707-16.
21.Silverstein MJ, Poller DN, Waisman JR, et al. Prognostic
classification of breast ductal carcinoma-in-situ. Lancet.
1995;345:1154-7.
22.Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to
predict local recurrence risk for ductal carcinoma in situ of the
breast. J Natl Cancer Inst. 2013;105:701-10.
23.Rakovitch E, Nofech-Mozes S, Hanna W, et al. A population-based
validation study of the DCIS Score predicting recurrence risk in
individuals treated by breast-conserving surgery alone. Breast Cancer
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24.Raldow AC, Sher D, Chen AB, et al. Cost effectiveness of the Oncotype
DX DCIS Score for guiding treatment of patients with ductal carcinoma in
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25.Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of
Breast Radiotherapy (START) trials of radiotherapy hypofractionation for
treatment of early breast cancer: 10-year follow-up results of two
randomised controlled trials. Lancet Oncol. 2013;14:1086-94.
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hypofractionated radiation therapy for breast cancer. N Engl J Med.
2010;362:513-20.
27.Ciervide R, Dhage S, Guth A, et al. Five year outcome of 145 patients
with ductal carcinoma in situ (DCIS) after accelerated breast
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28.Lalani N, Paszat L, Sutradhar R, et al. Long-term outcomes of
hypofractionation versus conventional radiation therapy after
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Int J Radiat Oncol Biol Phys. 2014;90:1017-24.
29.Shah C, Vicini F, Wazer DE, et al. The American Brachytherapy Society
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Accessed July 9, 2017.

June 2008

参考文献

United States放射性治疗协会(ACWrangler)和美利哥国家综合癌症网络(NCCN)指南协理扶持放射性治疗作为具有DCIS病人常规疗法。因为,未有分明性数据证实方可屏弃放射性治疗。然则年龄较大和/或有显著合并症伤者单做乳房肿瘤切除。那个指南中提到的影响治疗决策的因素有,伤者年龄、合并症、局地复发的恐怕(基于肿瘤级别、边缘、受体状态)等。须要记住的是三级以上或边缘中性(neuter gender)肿瘤病者复发风险高。

June 2008

原标题:图解 | 单克隆免疫性球蛋白相关性肾病(进阶版)

ACR指南和NCCN指南

Phase 1

澳门新葡8455最新网站 3

DCIS治疗去不掉放疗

Phase 3

1、 Kourelis TV, Kumar SK, Gertz MA, Lacy
MQ,Buadi FK, Hayman SR, et al.:
Coexistentmultiplemyeloma or increased bone
marrowplasma cells define
equally high-risk populationsin
patients with immunoglobulinlight
chain amyloidosis. J Clin Oncol
31:4319–4324,
2013.

展望因素能够帮衬医务卫生人士区分哪些伤者更合乎做放射性治疗。前面所讲的Smith预测验评定分是实惠的臆想工具;另二个评分工具Van
Nuys预测指数,但不曾普遍运用,未有得到外界普遍认同。肿瘤基因分析成为区分低、中、高危机DCIS伤者的新措施。先前关系的ECOG亚组分析结果呈现,低、中、高风险DCIS病人浸润性复发率分别为4%、1贰%、1玖%。近年来的大样本量基因分析再度评释Oncotype
DX
DCIS评分能够测度局地复发。方今,关怀点在低风险病人的高复发率(10年复发率为一三%)和性价比。预测工具或肿瘤基因检验能够区分哪些病人受益于援助放射性治疗的数据较少。在某些病例中,这么些工具得以辅助医师和病者决定是不是利用放射疗法。

View MoreCollapse

14、 Aishwarya Ravindran, Ronald S. Go, Fernando C.
Fervenza and Sanjeev Sethi. Thrombotic microangiopathy associated with
monoclonal gammophathy. Kidney Int 91:691-698, 2017

DCIS治疗去放射性治疗的尝尝

NCT00639158

The Complexity and Heterogeneity of
Monoclonal Immunoglobulin-Associated Renal Diseases. J Am Soc Nephrol.
2018 Jul;29(7):1810-1823.

另2个关心点是支援放射性治疗DCIS的治病周期。随机临床试验结果显示,全乳房大分割放疗(3周)与正式放射性治疗(5周)的疗效和安全性相同。加拿大单中央试验和区域分析斟酌也观测了大分割放射疗法治疗DCIS病者效果。其它,乳腺局地加快放射性治疗时间低于1周(帮助放射性治疗),且并未有减退局地控制率,可看做特定DCIS病者的行业内部治疗方案。特定DCIS病者接受大分割和乳腺局地加快放射性治疗能减小治疗时间超越一半,既能治疗肿瘤,又能确定保障胸部完整性。

NCT00673881

责编:

由于放射疗法未能延长伤者总生存时间,研讨人口观望了低危害DCIS病人不用放射性治疗的法力。U.S.西部肿瘤合营组(ECOG)E51玖四试验纳入肿瘤大小≤二.5cm的低级别/中等级别DCIS伤者、肿瘤大小≤壹.0cm的高级别DCIS伤者共700名。肿瘤边缘中性(neuter gender)最小距离为叁mm。随同访问1二年后,3/陆级DCIS伤者产生同侧浸润性麦格综合征复发率(IBT本田CR-V)为14%、3级DCIS病人产生IBT奥迪Q5为二五%。在那里面两组的复发率都保持平静状态。

AbbVie (prior sponsor, Abbott)-AbbVie

图解 | 单克隆免疫性球蛋白相关性肾病

四个里程碑式试验明确了放射疗法治疗DCIS的地位。陆个随机试验比较了胸部肿瘤切除后救助放射性治疗和无放射性治疗的效能,分别是美利坚合众国国家眼科学技术协会助治疗乳腺和肠道项目(NSABP)B-一七试验、SweDIC试验、欧洲癌症研商和看病团队10八伍三检查评定、大不列颠及苏格兰联合王国癌症切磋合作组织考试。各类试验都认证加用放射疗法能裁减5/10的同侧浸润性妊高征复发率(IBTLacrosse)。全数6个钻探都证实了加用放射性治疗能鲜明收缩浸润性复发、收缩宫颈癌过逝率。可是这个考试或对这几个考试的荟萃分析结果未能证实放射疗法能拉开伤者总生存时间。

NCT00681395

12、 Vignon M, Javaugue V, Alexander MP, El-Karoui
K, Karras A, Roos-Weil D, et al.: Currentanti-myeloma therapies in renal
manifestationsof monoclonal light
chain-associatedFanconi syndrome: A retrospectiveseries of
49 patients. Leukemia 31: 123–129,2017.

1967年间,第贰次发现了乳腺导管内原位癌(DCIS)。在美利坚协作国,每年有五千0例DCIS病例,约占新确诊乳头内陷病例的伍分之1。就算DCIS属于癌前病变,不过要求积极治疗。若是不治疗,DCIS能够发展为浸润性癌,引起谢世。200五年的回想性传播疾病例分析结果展现,在个别病例中,无积极治疗的细菌性阴道炎病逝率约为一成-伍分一。如今的数量展现,积极治疗后的DCIS驾鹤归西率只有叁.三%。那种分歧与一成的同侧浸润性阴道炎复发率(IBT猎豹CS陆)有关,固然接受治疗(无放射治疗)的患儿也是那样。近日,依据多少个里程碑式试验结果来明确DCIS治疗方案。乳房肿瘤切除必须与放射治疗合用,以便减弱部分复发率(尤其是浸润性复发),随后加用抗雌激素治疗升高部分控制率。但是对DCIS的医治特点和基因特点有越多精晓后,治疗相关风险不仅涉及到看病强度和不良反应,而且关系到人身、心思、经济等各方面。

April 2008

5、 Ramos-CasalsM, Stone JH,CidMC, Bosch
X:The cryoglobulinaemias. Lancet 379: 348–360,
2012.

丹娜法伯医院的试验提供了另一份数据。该试验纳入肿瘤大小<二.5cm、肿瘤边缘阴性≥一cm、百分之五十级DCIS术后伤者。在那一个低危机伤者中,八年的部分复发率>一三%,在那之中三分之1的患儿是浸润性复发。

[2].Mohiuddin SM, Pepine CJ, Kelly MT et al. Efficacy and safety of
ABT-335 (fenofibric acid) in combination with simvastatin in patients
with mixed dyslipidemia: a phase 3, randomized, controlled study. Am
Heart J. 2009
Jan;157(1):195-203.

4、 Bhutani G, Nasr SH, Said SM, Sethi
S,Fervenza FC,Morice WG, et
al.:Hematologiccharacteristics of proliferative
glomerulonephritideswith nonorganized monoclonalimmunoglobulin deposits. Mayo Clin
Proc90: 587–596,2015.

结论:研商者认为保乳手术救助放射性治疗是绝超越四分之一乳腺导管内原位癌病人的科班治疗方案。放射性治疗不仅减少1些复发,而且还足以减掉浸润性复发。预测后果评分和肿瘤基因检查测试等工具尚不可能分别哪些伤者接受放射性治疗后减去浸润性复发。

University of Pennsylvania-Abbott

10、 Rajkumar SV, Dimopoulos MA, Palumbo
A,Blade J, Merlini G, Mateos M-V, et al.:
Internationalmyelomaworking group updatedcriteria
for the diagnosis of multiple myeloma.Lancet
Oncol 15: e538–e548, 2014.

澳门新葡8455最新网站 4

Dyslipidemia-Coronary Heart Disease-Mixed Dyslipidemia

3、 Lin J,Markowitz GS, Valeri AM, Kambham
N,Sherman WH, Appel GB, et al.: Renalmonoclonal immunoglobulin deposition
disease:The disease spectrum. J Am Soc
Nephrol12: 1482–1492, 2001.

分明放射疗法治疗DCIS的身份

NCT00680017

7、 Sethi S, Cuiffo BP, Pinkus GS, Rennke
HG:Crystal-storing histiocytosis involving
thekidney in a low-grade B-cell
lymphoproliferativedisorder.AmJ Kidney Dis 39:
183–188,2002.

有点人认为,由于并未有人身自由临床试验能证实帮衬放射性治疗能延长病人总生存时间,那么很多DCIS病人乳房肿瘤切除后不用接受放射性治疗。在随同访问进程中精心监测病情,如有指征时放射性治疗可看做挽救性治疗。可是放射性治疗无法拉开病人生活时间不对等没效果。10年的DCIS相关宫颈息肉特定过逝率唯有三%。

NCT00300469

事先的始末参见

Smith等在200陆年第贰遍提议了展望评分方法,涉及会诊年龄、肿瘤级别、肿瘤大小、粉刺病史等要素。Sagara等的考察结果彰显,预测后果评分五分或陆分(包蕴4分以上评分)病人使用放射性治疗后减去了12分之7的病逝率,预测后果评分四分病员中也存在5%的反差(P=0.0叁)。这一个意识在最初乳房棘球蚴病同盟组织浸润性癌荟萃分析中收获印证,成为早期浸润性非淋菌性尿道炎病者接受保乳手术和放射性治疗能减小与世长辞率的基本点证据。

NCT00683176

8、 Gupta V, El TersM, Kashani K, Leung N,
NasrSH: Crystalglobulin-induced nephropathy.
JAm Soc Nephrol 26: 525–529, 2015.

相比总生存时间上的显然性差别,要求充足大的样本量。那正是基于人口的数目变得实惠的案由。大数据不仅能够提供国家主旨景况,而且能够让医师有充裕的样本量评估治疗方案是或不是对疾病发生鲜明医疗效果。

Dyslipidemia-Coronary Heart Disease-Mixed Dyslipidemia

(友情提醒:图片可点开放大,看得更精通)

对米利坚DCIS治疗和疗效的监测、流行病学、最后效果的切磋(Sagara等)结果给了些提醒。三千0名伤者的寿终正寝率约为2%。不过加用放射性治疗能减低驾鹤归西率,有放射性治疗一.8%
vs
无放射性治疗贰.壹%。纵然有那么些创新,约有百分之四十的DCIS病人从未接受过放射性治疗。值得注意的是放射性治疗改正病人生活时间与以下二个因素有关:高级别肿瘤、年龄低于陆十虚岁、较大肿瘤。这几个发现是个别随机对照试验中得不到涉及的。

Phase 1

参考文献:

Radiant Research

9、 Vankalakunti M, Bonu R, Shetty S, Siddini
V,Babu K, Ballal SH: Crystalloid
glomerulopathyin monoclonal gammopathy of renalsignificance (MGRS). Clin Kidney J 7: 296–298,
2014.

NCT00680017

澳门新葡8455最新网站 5

Adverse Events-Pharmacokinetic Variables

13、 Ravindran A, Fervenza FC, Smith RJ, Sethi
S:C3 glomerulopathy associated with
monoclonalIg: A distinct subtype. Kidney Intdoi:
10.1016/j.kint.2018.01.037.

Phase 3

6、 Nasr SH, Fidler ME, Cornell LD, Leung
N,Cosio FG, Sheikh SS, et al.:
Immunotactoidglomerulopathy: Clinicopathologic and
proteomicstudy. Nephrol Dial Transplant 27:4137–4146, 2012.

NCT00728780

11、 Stokes MB, Valeri AM, Herlitz L, Khan
AM,Siegel DS, Markowitz GS, et al.: Light
chainproximal tubulopathy: Clinical and
pathologiccharacteristics in the modern
treatmentera. J Am Soc Nephrol 27: 1555–1565,
2016.

AstraZeneca

澳门新葡8455最新网站 6

NCT00826358

NCT00491530

February 2009

Phase 3

April 2007

Phase 3

AstraZeneca

生物活性

June 2007

Phase 1

Abbott

NCT00491530

NCT00826358

June 2007

NCT00683176

NCT00681525

February 2008

AstraZeneca

Abbott

AstraZeneca

Abbott

April 2007

Phase 1

Abbott

February 2008

Dyslipidemia

AstraZeneca

September 2006

NCT00681525