Abstract:
:Meprins are zinc-dependent metalloproteinases that are highly expressed in the brush-border membranes of both the kidney and the intestines. Meprins are capable of proteolytically degrading extracellular matrix proteins, proteolytically processing bioactive proteins, and play a role in inflammatory processes. In this study, the function of meprin A in the acute kidney injury (AKI) model of cisplatin nephrotoxicity was examined. Normal linear localization of meprin A in the brush border membranes of proximal tubules was altered in AKI. The meprin A alpha-subunit was detected in the urine of both control and cisplatin-treated mice. A cleaved product of the meprin A beta-subunit, undetected in the urine of control mice, was found to be significantly increased in the urine during the progression of cisplatin nephrotoxicity. The excretion of this beta-fragment was found to be before the rise in serum creatinine and blood urea nitrogen (BUN) suggesting usefulness as a biomarker for AKI. Pretreatment of mice with a meprin A inhibitor afforded protection from cisplatin nephrotoxicity as reflected by significant decreases in serum creatinine, BUN, and the excretion of kidney injury molecule-1. These decreases in serum and urine biomarkers were accompanied by significant decreases in histologic markers such as leukocyte infiltration and apoptosis. Meprin A appears to be an important therapeutic target and urinary excretion appears to be a potential biomarker of AKI.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Herzog C,Seth R,Shah SV,Kaushal GPdoi
10.1038/sj.ki.5002189subject
Has Abstractpub_date
2007-05-01 00:00:00pages
1009-18issue
10eissn
0085-2538issn
1523-1755pii
S0085-2538(15)52252-7journal_volume
71pub_type
杂志文章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:Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the pathogenesis of diabetic nephropathy. The objective of this study was to determine whether alterations of the plasma and urinary VEGF and sFLT-1 levels were related to the stages and risk factors of diabetic nephropathy. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00067.x
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00392.x
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Previous experiments from our laboratory have demonstrated that HKalpha(2) coimmunoprecipitated with beta(1)-Na(+),K(+)-ATPase. Although HKalpha(2) is expressed abundantly in the apical membrane of distal colon, the demonstration that beta(1) localizes to this same membrane in distal colon has not been demon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00856.x
更新日期:2004-09-01 00:00:00
abstract::The clinical utility of cisplatin is limited by nephrotoxicity. Oh et al. report that β-lapachone prevents this nephrotoxicity but not cisplatin's cytotoxicity for cancers. In addition to its potential clinical importance, the beneficial effect of β-lapachone on cisplatin acute kidney injury may illustrate fundamental...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.419
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:The long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear. METHODS:The United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00636.x
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND:Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is mark...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00580.x
更新日期:2004-05-01 00:00:00
abstract::The acutely injured mammalian kidney mounts a cellular and molecular response to repair itself. However, in patchy regions such intrinsic processes are impaired and dysregulated leading to chronic kidney disease. Currently, no therapy exists to treat established acute kidney injury per se. Strategies to augment human ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.07.030
更新日期:2018-01-01 00:00:00
abstract::Chronic kidney disease (CKD) has received increased attention as a leading public health problem worldwide. Globally surveillance systems for kidney disease are still lacking, especially in developing countries like China, which constitutes an obstacle to develop effective preventive strategies. China Kidney Disease N...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.11.011
更新日期:2019-03-01 00:00:00
abstract::Because the size of renal cysts in the native kidneys of patients with ADPKD who have been transplanted was found to be reduced when rapamycin was the immunosuppressant, we tested the involvement of the mTOR pathway in cyst enlargement. Here, male pcy mice, with mutation in one of the nephronophthisis genes, were trea...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.147
更新日期:2009-07-01 00:00:00
abstract::Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.201
更新日期:2008-09-01 00:00:00
abstract::It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.376
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:The aim of this study was to establish whether there is a differential effect of mode of dialysis, hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) on the dyslipidemia of renal failure. METHODS:The lipoprotein profile was determined in 61 non-diabetic patients on chronic HD (N = 30) an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00375.x
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND:Dopamine (DA) is thought to regulate renal proximal transport through the inhibition of the Na+,K+-ATPase and/or Na+/H+ exchanger. Defects in this dopaminergic system are proposed to be a pathogenic factor of genetic hypertension. However, microperfusion studies have not consistently confirmed direct tubular...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00873.x
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Podocytes play an important role in the development of proteinuria and focal glomerulosclerosis. Previously we have demonstrated that a combination of two monoclonal antibodies (mAb) against aminopeptidase A (APA), an enzyme present on podocytes, induces a massive acute albuminuria in mice. The present study...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00428.x
更新日期:2002-07-01 00:00:00
abstract::Hypoalbuminemia is the most powerful predictor of mortality in end-stage renal disease. Since protein-calorie malnutrition can decrease albumin synthesis it is assumed that hypoalbuminemia results principally from malnutrition in these patients, but albumin synthesis may also be decreased as part of the acute-phase re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.321
更新日期:1995-08-01 00:00:00
abstract::It is well known that uremia causes an increase in the serum anion gap (AG); however, whether changes in the AG occur earlier in the course of chronic kidney disease is not known. Here we investigated whether different measures of the AG, as a marker of kidney function, are associated with mortality. To do this, we an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.196
更新日期:2012-09-01 00:00:00
abstract::Genetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polym...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.251
更新日期:2010-10-01 00:00:00
abstract::The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding activity that specifically recognizes an 8 bp hypoxia response element (HRE) known to be essential for oxygen-regulated erythropoietin gene expression. In electrophoretic mobility shift assays (EMSAs) HIF-1 DNA binding activity is only detecta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.80
更新日期:1997-02-01 00:00:00
abstract::Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.482
更新日期:2013-06-01 00:00:00
abstract::Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.024
更新日期:2018-08-01 00:00:00
abstract::Recent advances have led to a greater appreciation of how mitochondrial dysfunction contributes to diverse acute and chronic pathologies. Indeed, mitochondria have received increasing attention as a therapeutic target in a variety of diseases because they serve as key regulatory hubs uniquely situated at crossroads be...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2017.05.034
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:High-dose folinic acid is used to accelerate methotrexate elimination to avoid renal toxicity of the drug. The present study was carried out to examine the role of the renal organic anion transporters OAT-K1 and OAT-K2 in the urinary excretion of methotrexate, especially in the methotrexate-folinic acid resc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0600031058.x
更新日期:2001-09-01 00:00:00
abstract:BACKGROUND:To study the molecular mechanism responsible for cadmium-induced Fanconi syndrome, an in vitro mouse model has been used. We have previously shown that exposure of primary cultures of kidney cortical cells to micromolar concentrations of cadmium inhibited uptake of the glucose analog, [14C] methyl alpha-d-gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00201.x
更新日期:2003-10-01 00:00:00
abstract::Defective cholesterol metabolism primarily linked to reduced ATP-binding cassette transporter A1 (ABCA1) expression is closely associated with the pathogenesis and progression of kidney diseases, including diabetic kidney disease and Alport Syndrome. However, whether the accumulation of free or esterified cholesterol ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.06.040
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:While metabolically generated oxidants are produced locally in experimental glomerular diseases, little is still known of their significance and the respective scavenger systems in human glomerular diseases. METHODS:Here we studied kidneys from patients with congenital nephrotic syndrome of the Finnish type...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002481.x
更新日期:2001-02-01 00:00:00
abstract::Isolated perfused rat kidneys were passively sensitized by addition of either mouse ascitic fluid containing monoclonal IgE against dinitrophenol (DNP) or DNP-specific purified IgE. After washing the organ, defined doses of DNP-bovine serum albumin were given as bolus injection via the kidney artery. Antigen challenge...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.197
更新日期:1987-08-01 00:00:00
abstract::Adaptive increases in renal bicarbonate reabsorption occur in response to acute increases in filtered bicarbonate (FLHCO3). In a previous study, we showed that an increase in FLHCO3 induced by plasma volume expansion increased the Vmax for Na+/H+ exchange activity in renal cortical brush border membrane vesicles (BBMV...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.351
更新日期:1997-08-01 00:00:00
abstract::The molecular mechanism of Na+ and phosphate transport by the intestinal brush border membrane Na+/phosphate cotransporter was examined using anion and cation exchange columns interfaced to a light-activated microsecond timer. The nature of ion:cotransporter interaction was examined for sensitivity to itself versus no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.141
更新日期:1996-04-01 00:00:00
abstract::Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.115
更新日期:2012-07-01 00:00:00