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 followed by mass spectrometry was used to identify novel antigen(s) in PLA2R-negative membranous nephropathy. An initial pilot mass spectrometry study in 35 cases of PLA2R-negative membranous nephropathy showed high spectral counts for neural tissue encoding protein with EGF-like repeats, NELL-1, in six cases. Mass spectrometry failed to detect NELL-1 in 23 PLA2R-associated membranous nephropathy and 88 controls. NELL-1 was localized by immunohistochemistry, which showed bright granular glomerular basement membrane staining for NELL-1 in all six cases. Next, an additional 23 NELL-1 positive cases of membranous nephropathy were identified by immunohistochemistry in a discovery cohort of 91 PLA2R-negative membranous nephropathy cases, 14 were confirmed by mass spectrometry. Thus, 29 of 126 PLA2R-negative cases were positive for NELL-1. PLA2R-associated membranous nephropathy and controls stained negative for NELL-1. We then identified five NELL-1 positive cases of membranous nephropathy out of 84 PLA2R and THSD7A-negative cases in two validation cohorts from France and Belgium. By confocal microscopy, both IgG and NELL-1 co-localized to the glomerular basement membrane. Western blot analysis showed reactivity to NELL-1 in five available sera, but no reactivity in control sera. Clinical and biopsy findings of NELL-1 positive membranous nephropathy showed features of primary membranous nephropathy. Thus, a subset of membranous nephropathy is associated with accumulation and co-localization of NELL-1 and IgG along the glomerular basement membrane, and with anti-NELL-1 antibodies in the serum. Hence, NELL-1 defines a distinct type of primary membranous nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sethi S,Debiec H,Madden B,Charlesworth MC,Morelle J,Gross L,Ravindran A,Buob D,Jadoul M,Fervenza FC,Ronco Pdoi
10.1016/j.kint.2019.09.014subject
Has Abstractpub_date
2020-01-01 00:00:00pages
163-174issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30995-0journal_volume
97pub_type
杂志文章abstract:BACKGROUND:A nationwide survey of urolithiasis in Japan was made in order to evaluate the chronological trend of upper urinary tract stones in the Japanese. It succeeded previous studies done in 1955, 1966, 1979, and 1990. METHODS:All outpatient visits to urologists that resulted in a diagnosis of first-episode upper ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00754.x
更新日期:1999-11-01 00:00:00
abstract:BACKGROUND:Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy (RRT), concerns remain regarding the bioincompatible nature of standard PD fluid. In order to evaluate whether a newly formulated fluid of neutral pH, and containing low levels of glucose degradation products (GDP), resu...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1523-1755.2004.00747.x
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:The p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00044.x
更新日期:2001-12-01 00:00:00
abstract::We have previously established that interferon (IFN)-gamma stimulated, antigen-pulsed tubular epithelial cells (TEC) stimulate antigen (Ag) specific activation of T cell hybridomas to express IL-2. In contrast, these Ag pulsed TEC do not stimulate T helper 1 (Th1) clones to proliferate, but rather render them unrespon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.147
更新日期:1994-04-01 00:00:00
abstract::Pulse wave velocity (PWV) was measured in the aorta, right leg and arm of 90 control subjects (CS) and 92 hemodialysis patients (HD) of the same age and mean arterial pressure (MAP). Blood chemistry, including blood lipids, and echographic dimensions of the aorta, were measured in all subjects. Presence of aortic calc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.19
更新日期:1990-01-01 00:00:00
abstract::The clinical value of biocompatible peritoneal dialysis solutions is uncertain because of inconsistent findings in randomized controlled trials. A systematic review by Cho et al. examining 20 such trials suggests a beneficial effect on residual renal function. However, the finding is not robust and may relate to decre...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.303
更新日期:2013-11-01 00:00:00
abstract::In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.242
更新日期:1991-09-01 00:00:00
abstract::Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascul...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.644
更新日期:2009-05-01 00:00:00
abstract::A number of clinical laboratory and biopsy-derived parameters were assessed for their prognostic significance in the short (24 months), intermediate (60 months) and long terms in 45 patients (43 female, 2 male) with diffuse proliferative lupus glomerulonephritis (DPGN). The factors evaluated were serum creatinine (SCr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.211
更新日期:1988-10-01 00:00:00
abstract::Unilateral ureteral obstruction results in marked changes in renal function throughout the nephron, including impaired acid and potassium secretion and salt wastage. The nephron site believed responsible for the acidification defect is the collecting duct. It has been presumed, although not demonstrated, that the cell...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.11
更新日期:1990-01-01 00:00:00
abstract::Normal urine contains thousands of proteins, largely due to the presence of 'exosomes,' tiny vesicles secreted into the urine by renal epithelial cells. These exosomes, demonstrated by Keller and colleagues to be also retrievable from amniotic fluid, offer great promise for future disease biomarker discovery studies. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002510
更新日期:2007-11-01 00:00:00
abstract::Defective recycling of megalin consequent to impaired phosphatidylinositol metabolism has been implicated as a mechanism causing tubular proteinuria in patients with Lowe syndrome. In this issue, Berquez et al. describe an innovative approach using a clinically approved drug to "rebalance" phosphatidylinositols and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.06.018
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND:The clinical demographics of chronic dialysis patients are changing worldwide. However, long-term data from regional dialysis registries have not yet been analyzed and reported. METHODS:The Okinawa Dialysis Study (OKIDS) registry included all chronic dialysis patients treated in Okinawa, Japan, since 1971. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00147.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:In addition to nitric oxide (NO) and prostacyclin (PGI2), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00910.x
更新日期:2003-05-01 00:00:00
abstract::The pathogenesis of the multiple structural lesions in diabetic nephropathy remains debated, and likely is multifactorial. The uniform thickening of the renal basement membranes lining the glomerular and tubular elements appears to be a consequence of the metabolic perturbations which are directly related to hyperglyc...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1993.19
更新日期:1993-01-01 00:00:00
abstract:INTRODUCTION:Transforming growth factor-beta (TGF-beta) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00919.x
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in thr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00904.x
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Proteinase 3 is the major autoantigen in Wegener's granulomatosis (WG). Membrane PR3 expression is bimodal; low expressing cells (mPR3(low)) can be distinguished from cells with high expression (mPR3(high)) within a given individual. High mPR3 expression is a WG risk factor and is associated with relapse. Ho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00640.x
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. The chromosomal locus for MCKD2 was localized on chromosome 16p12. Within this chromosomal region...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00269.x
更新日期:2003-11-01 00:00:00
abstract::This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this seg...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1986.13
更新日期:1986-01-01 00:00:00
abstract::IgA1 proteins from sera of patients with IgA nephropathy (IgAN) are galactosylated to a lesser degree than those from healthy controls. The increased reactivity of intact or de-sialylated serum IgA1 with N-acetylgalactosamine (GalNAc)-specific lectins, Helix aspersa (HAA) and Caragana arborescens (CAA) and de-sialylat...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.361
更新日期:1997-08-01 00:00:00
abstract::A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.368
更新日期:1994-10-01 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:BACKGROUND:Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00933.x
更新日期:2003-05-01 00:00:00
abstract::Many approaches to blocking profibrotic TGFbeta overexpression are under way. Therapeutic targeting of TGFbeta-Smad signaling holds promise for slowing or halting progressive renal disease. In this issue, Fukasawa et al., using the unilateral ureteral obstruction model, provide a new target for therapeutic interventio...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000260
更新日期:2006-05-01 00:00:00
abstract::Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-beta1, a key cytokine associated with kidney disease, responds to circul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.109
更新日期:2010-08-01 00:00:00
abstract::As the worldwide prevalence of end-stage renal disease increases it is important to evaluate the rate of living kidney donation in various countries; however there is no comprehensive global assessment of these rates. To measure this, we compiled data from representatives, renal registries, transplant networks, publis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.20
更新日期:2009-05-01 00:00:00
abstract::Monocyte and macrophage markers are among the most highly overexpressed genes in cpk mouse kidneys with severely progressive renal cystic disease. We show here that one of these markers, CD14, is abnormally transcribed, activated and shed in cystic kidneys. However, these abnormalities were not associated with an incr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.175
更新日期:2010-09-01 00:00:00
abstract::11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.91
更新日期:1994-03-01 00:00:00
abstract::The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.260
更新日期:1992-07-01 00:00:00