Abstract:
:Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuates IRI, cellular inflammation, and long-term effects on renal interstitial fibrosis. We used a porcine model of kidney IRI and used Texas Biotechnology Corporation (TBC)-1269, a selectin ligand inhibitor. Renal function, tissue inflammation, and tubulointerstitial fibrosis development were evaluated up to 16 weeks. Both warm and cold ischemia models were studied for relevance to native and transplant kidney injury. Pigs treated with TBC-1269 during 45 min of warm ischemia (WI) showed significantly increased glomerular filtration rate compared to control animals. In pigs with severe IRI (WI for 60 min), TBC-1269 treatment during IRI significantly increased renal recovery. Cellular inflammation was strongly reduced, particularly influx of CD4 cells. Quantitative measurement of fibrosis by picrosirius red staining showed strong reduction in TBC-1269-treated groups. TBC-1269 also reduced cold IRI, inflammation, and fibrosis in kidneys preserved for 24 h at 4 degrees C and autotransplanted. The selectin ligand inhibitor TBC-1269 provides a novel and effective approach to attenuate IRI in both warm and cold ischemia in large mammals, in both short and long terms. Selectin ligand inhibition is an attractive strategy for evaluation in human kidney IRI.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Jayle C,Milinkevitch S,Favreau F,Doucet C,Richer JP,Deretz S,Mauco G,Rabb H,Hauet Tdoi
10.1038/sj.ki.5000335subject
Has Abstractpub_date
2006-05-01 00:00:00pages
1749-55issue
10eissn
0085-2538issn
1523-1755pii
S0085-2538(15)51353-7journal_volume
69pub_type
杂志文章abstract:BACKGROUND:It is not known to what extent intravascular phenotypic alterations in adhesion molecule expression induced by hemodialysis influence the recruitment of monocytes and their ability to up-regulate CD11b at the local site of inflammation in the interstitium. Using a skin suction chamber technique, we addressed...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00060.x
更新日期:2000-05-01 00:00:00
abstract::Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosupp...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002306
更新日期:2007-06-01 00:00:00
abstract::We have developed an immunological procedure for measuring advanced glycosylation end-products (AGEs) in serum. Using this method, we measured AGEs in healthy volunteers, patients with diabetes, renal failure without treatment and in patients with renal failure, treated with hemodialysis (HD) or continuous ambulatory ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.262
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:Acute renal allograft rejection with intimal arteritis is designated by the widely used Banff 97 classification as type 2A or 2B depending on the extent of arteritis, without regard to interstitial inflammation or tubulitis. We examined whether the distinction between type 2A and 2B is relevant to short- and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00254.x
更新日期:2002-04-01 00:00:00
abstract::Early kidney transplant results in children lagged behind corresponding results in adults. Multiple advances over the past three decades have eliminated that gap. Most children now have equal or superior long-term allograft and patient survival compared with adult recipients. However, black children in the United Stat...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.366
更新日期:2015-03-01 00:00:00
abstract::Stimulation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) production was studied during in vitro hemodialysis (HD) of whole blood using cuprammonium (Cup) or polysulfone (PS) dialyzers. In the absence of LPS, circulation of whole blood for two hours through Cup or PS dialyzers was not suffici...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1990.12
更新日期:1990-01-01 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::Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin-angiotensin-aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.270
更新日期:2015-12-01 00:00:00
abstract::Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.195
更新日期:1980-12-01 00:00:00
abstract::Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic b...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2018.02.029
更新日期:2018-08-01 00:00:00
abstract::Erythropoiesis stimulating agent (ESA) treatment has been a major advance in the care of patients with kidney disease, resulting in reduced symptoms and blood transfusions, and improved quality of life. Recent studies, however, have indicated that attempts to treat to near normal Hgb targets may result in increased ri...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.467
更新日期:2009-02-01 00:00:00
abstract::Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outc...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2015.12.001
更新日期:2016-03-01 00:00:00
abstract::A morphometric technique is used to estimate the absolute and relative surface areas of the brush border microvilli and cell walls bordering lateral intercellular spaces. In isolated, perfused proximal tubule from rabbit, the luminal and lateral surfaces are equal in area. For proximal convoluted tubules (PCT) each su...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.125
更新日期:1975-12-01 00:00:00
abstract::Modern dietary habits are characterized by high-sodium and low-potassium intakes, each of which was correlated with a higher risk for hypertension. In this study, we examined whether long-term variations in the intake of sodium and potassium induce lasting changes in the plasma concentration of circulating steroids by...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.15
更新日期:2011-08-01 00:00:00
abstract::The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.63
更新日期:2009-06-01 00:00:00
abstract::In view of the increasing concern about methicillin-resistant Staphylococcus aureus (MRSA) infections, we studied the characteristics and outcome of MRSA nasal carriage and infections in our CAPD program. All patients entering into the CAPD program from January 1989 to December 1991 were enrolled into the study. The p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.191
更新日期:1993-06-01 00:00:00
abstract::In the epidemiologic study of end-stage renal disease (ESRD), accurate adjustment for comorbidity is essential to controlling bias in the comparison of outcomes across groups of patients or dialysis facilities. Liu et al. derive and validate a novel comorbidity index using data from the United States Renal Data System...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.431
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model. METHODS:Rats were treated for 12 weeks with either lead...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00670.x
更新日期:1999-10-01 00:00:00
abstract::Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that acts primarily on the kidney and parathyroid. With declining kidney function there is an increase in circulating FGF23 levels, which is associated with vascular calcification and mortality in chronic kidney disease. Whether FGF23 exerts direct ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.332
更新日期:2014-05-01 00:00:00
abstract::The kallikrein-kininogen-kinin system (KKK) has been implicated in the renal sodium excretion response to changes in dietary sodium. However, both increases and decreases in the activity of this system have been observed when urinary sodium excretion is augmented by a variety of maneuvers. To further evaluate the pote...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1987.74
更新日期:1987-03-01 00:00:00
abstract::Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.482
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Hemodialysis access thrombosis is a significant cause of morbidity for hemodialysis patients and results from decreased access flow caused by venous outflow tract stenosis. Ultrasound dilution (UD) is a practical, noninvasive, and reliable indicator of access flow and is effective in predicting venous stenos...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2001.00753.x
更新日期:2001-06-01 00:00:00
abstract::We examined the role of the plasminogen activator/plasmin system in extracellular matrix (ECM) degradation by human mesangial cells cultured on thin films of 125I-labeled ECM (Matrigel). ECM degradation (release of 125I into the medium) was dependent on exogenous plasminogen, proportional to the number of mesangial ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.150
更新日期:1995-04-01 00:00:00
abstract::Recent studies suggest the presence of local angiotensin generating system in the kidney. By using in situ hybridization technique, mRNA for angiotensinogen has been shown to be present in the proximal tubule. In the present study, we have attempted to examine the production of angiotensinogen and renin-like activity ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.117
更新日期:1991-05-01 00:00:00
abstract::Thrombotic microangiopathy (TMA) is a poorly recognized cause of collapsing glomerulopathy. The frequency and significance of collapsing glomerulopathy associated with renal TMA have not been specifically studied in native kidney biopsy specimens. Here we retrospectively documented clinicopathologic features of 53 pat...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.07.021
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Podocyte loss contributes to the development of glomerulosclerosis. Although podocytes have been detected in the urine in certain glomerular diseases, the viability of detached cells is not known. METHODS:Urine was collected from rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00217.x
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:In renal cells, hyperosmolarity has been shown to induce the accumulation of myo-inositol, via the Na+/myo-inositol cotransporter (SMIT). Previously we showed that SMIT mRNA in the kidney is localized in the medullary thick ascending limb of Henle (TALH). Here we used renal cells derived from the rabbit oute...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00235.x
更新日期:1999-01-01 00:00:00
abstract::Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when p...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.314
更新日期:2009-10-01 00:00:00
abstract::The sympathetic nervous system modulates renal function through its receptors namely beta1 (cardiac output and renin release), alpha1 (systemic and renovascular constriction), and beta2 renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to i...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5001835
更新日期:2006-12-01 00:00:00
abstract::Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in the renal glomerulus, may oppose the deleterious effects of the type I receptor (AT1) through vasodilatation and growth inhibition. We determined whether t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000348
更新日期:2006-05-01 00:00:00