Abstract:
:Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Here we address this in a factor H mutant mouse (FHR/R) which developed complement-mediated TMA as well as macrovascular thrombosis caused by an aHUS-related factor H point mutation (mouse W1206R, corresponding to human W1183R). C5 deficiency and anti-C5 mAb treatment blocked all disease manifestations in FHR/R mice. C5aR1 gene deficiency prevented macrovascular thrombosis in various organs but did not improve survival or reduce renal TMA. Conversely, C6 or C9 deficiency significantly improved survival and markedly diminished renal TMA but did not prevent macrovascular thrombosis. Interestingly, as they aged both FHR/R C6-/- and FHR/R C9-/- mice developed glomerular disease reminiscent of C3 glomerulonephritis. Thus, C5aR and C5b-9 pathways drove different aspects of disease in FHR/R mice with the C5aR pathway being responsible for macrovascular thrombosis and chronic inflammatory injury while the C5b-9 pathway caused renal TMA. Our data provide new understanding of the pathogenesis of complement-mediated TMA and macrovascular thrombosis in FHR/R mice and suggest that C5 blockade is more effective for the treatment of aHUS than selectively targeting the C5aR or C5b-9 pathway alone.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Ueda Y,Miwa T,Ito D,Kim H,Sato S,Gullipalli D,Zhou L,Golla M,Song D,Dunaief JL,Palmer MB,Song WCdoi
10.1016/j.kint.2019.01.009subject
Has Abstractpub_date
2019-07-01 00:00:00pages
67-79issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30050-Xjournal_volume
96pub_type
杂志文章abstract:BACKGROUND:Dendritic cells (DCs) uniquely serve as conduits between innate and cognate arms of the immune system. The normal kidney contains an extensive population of interstitial DCs but their role in the pathogenesis of acute renal injury is not known. METHODS:Renal DCs were studied by flow cytometric analysis of c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00502.x
更新日期:2005-09-01 00:00:00
abstract::Quartan malarial infection causes an immune complex nephritis in some individuals, which, once established, is sustained by mechanisms not yet fully explained, but which probably involve autoimmune processes. The presenting clinical and biochemical findings of the quartan malarial nephrotic syndrome are similar to tho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.103
更新日期:1979-07-01 00:00:00
abstract::Vascular sclerosis has been linked to many risk factors, including smoking, family history, low birth weight, and hypertension. In interesting studies, Goforth et al. show an increased rate of mutations in thrombophilic molecules in patients with vascular sclerosis in renal biopsies, suggesting yet another mechanism. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001721
更新日期:2006-08-01 00:00:00
abstract::In this study, we have evaluated 50 children (30 girls and 20 boys; mean age, 10.1 years) with a variety of renal diseases in whom renal biopsy specimens showed crescents in greater than or equal to 50% of glomeruli. Initial clinical features included edema in 61%; hypertension in 51%; gross hematuria in 73%; 3 to 4+ ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.30
更新日期:1985-02-01 00:00:00
abstract:BACKGROUND:The alteration of renal cell growth is one of the early abnormalities in the diabetic nephropathy. However, the effects of high glucose and its action mechanism in renal proximal tubule cell (PTC) proliferation have not been elucidated. METHODS:The effects of 25 mmol/L glucose on cell proliferation, thymidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051695.x
更新日期:2001-05-01 00:00:00
abstract::Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001679
更新日期:2006-09-01 00:00:00
abstract::Angiotensin II (Ang II) is a major contributor to the progression of renal fibrosis. Wang and colleagues provide evidence that signaling through the prolyl-4-hydroxylase domain (PHD)-hypoxia-inducible factor-1 (HIF-1) pathway mediates profibrotic effects of Ang II in rat renal medullary interstitial cells under normox...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.434
更新日期:2011-02-01 00:00:00
abstract::The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.03.019
更新日期:2018-08-01 00:00:00
abstract::An expression profile is a list based on a large scale sequencing of 1000 cDNA clones, showing the expressed genes and the abundance of their transcripts in a given cell or tissue (Okubo K et al: Nature Genet 2:173, 1992). We constructed an expression profile of mouse renal proximal tubules (PT) carefully isolated by ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00808.x
更新日期:1998-03-01 00:00:00
abstract::Transgenic rats [TGR; strain name TGR(mRen2)27] harboring the mouse Ren-2 renin gene have been recently generated as a model for the study of primary hypertension that offers the advantage of a clearly-defined genetic alteration. Expression of the mouse Ren-2 gene causes severe hypertension (200 to 260 mm Hg) which is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.4
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Bioimpedance, a noninvasive technique to analyze body composition, has attracted interest in determining body hydration in hemodialysis patients. However, the so-called whole-body (wrist-to-ankle) bioimpedance analysis (WBIA) is sensitive to changes in regional fluid distribution and tends to underestimate f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00588.x
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003855.x
更新日期:2001-03-01 00:00:00
abstract::Antibodies against purified rat-kidney-cortex pyruvate carboxylase were raised in rabbits. These polyspecific antibodies recognize pyruvate carboxylase enzymes alone without cross reactivity with other carboxylases as detected by immunoblotting. The abundance of pyruvate carboxylase in the various renal fractions was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.147
更新日期:1991-06-01 00:00:00
abstract::We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208 type ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000377
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:It is suggested that either arginine or its metabolites, nitric oxide and polyamines play a role in the renal hemodynamic alterations observed in the early stages of diabetes. Yet, the regulation of arginine transport in diabetic kidneys has never been studied. METHODS:Arginine uptake was determined in glom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00508.x
更新日期:2004-04-01 00:00:00
abstract::Prior studies reported associations of APOL1 nephropathy risk variants with subclinical atherosclerosis. However, these findings were limited to older individuals with high comorbidities. To evaluate this in younger individuals, we calculated associations of APOL1 risk variants (high risk [2 risk variants] vs. low ris...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.08.019
更新日期:2018-03-01 00:00:00
abstract::Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.224
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:The peritoneum is progressively denuded of its mesothelial cell monolayer in patients on continuous ambulatory peritoneal dialysis (CAPD). These alterations of the mesothelium cause membrane dysfunction and progressive peritoneal fibrosis. Integrins regulate cell motility and play an important role in wound ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00772.x
更新日期:2003-02-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract::Urinary proteomics is a promising tool for biomarker investigation, particularly in complex kidney diseases. Fabris and colleagues report that urinary laminin subunit alpha-2 is a potential diagnostic marker of medullary sponge kidney (MSK) disease by using a label-free quantitative proteomics platform and a clinicall...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.032
更新日期:2017-02-01 00:00:00
abstract::Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Lon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.327
更新日期:2013-01-01 00:00:00
abstract::Iron is critical for cellular, organismal, and possibly universal existence. Use of iron complexes to treat human diseases is ancient and is described in detail in Ayurveda/Siddha systems of medicine. Old aphorisms from Siddha medicine ("Alavukku Minjinal Amirdhamum Nanjagum," an elixir turns poisonous when taken in e...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.02.035
更新日期:2016-07-01 00:00:00
abstract::Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, converting heme to biliverdin, during which iron is released and carbon monoxide (CO) is emitted; biliverdin is subsequently converted to bilirubin by biliverdin reductase. At least two isozymes possess HO activity: HO-1 represents the isozyme...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5001565
更新日期:2006-08-01 00:00:00
abstract::Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.ki.5000088
更新日期:2006-03-01 00:00:00
abstract::We designed a study to provide reversibility and comparative injury data for several candidate urinary biomarkers of kidney injury in the United States Food and Drug Administration biomarker qualification process. The nephrotoxin gentamicin was given to rats once on each of three days and the animals were killed durin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.463
更新日期:2011-06-01 00:00:00
abstract::Females across their lifespan and certain male populations are susceptible to urinary tract infections (UTI). The influence of female vs. male sex on UTI is incompletely understood, in part because preclinical modeling has been performed almost exclusively in female mice. Here, we employed established and new mouse mo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.04.023
更新日期:2018-09-01 00:00:00
abstract::Serum fibroblast growth factor 23 (FGF23) is a novel phosphaturic factor and important for the regulation of inorganic phosphate (Pi) homeostasis. In this study, we examined an acute effect of oral Pi loading on serum FGF23 levels to clarify the role in rapid adjustment of serum Pi level. We performed a randomized, do...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5002000
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:The continuous chemical, physical, and inflammatory insults of prolonged continuous ambulatory peritoneal dialysis (CAPD) incite mesothelial cell responses, which may result in peritoneal fibrosis. The transforming growth factor-beta (TGF-beta), especially the isoform TGF-beta 1, has long been known to play ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00861.x
更新日期:2003-04-01 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::Renal proximal tubule cells from spontaneously hypertensive rats (SHR), compared with normotensive Wistar-Kyoto rats (WKY), have increased oxidative stress. The contribution of mitochondrial oxidative phosphorylation to the subsequent hypertensive phenotype remains unclear. We found that renal proximal tubule cells fr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.397
更新日期:2014-03-01 00:00:00