Abstract：
:Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in part be due to an inadequate comparability of human disease and animal models that often capture only a few aspects of disease. Here we overcome this limitation by developing a multimolecular noninvasive humanized readout of diabetic nephropathy based on urinary peptidomics. The disease-modified urinary peptides of 2 type 2 diabetic nephropathy mouse models were identified and compared with previously validated urinary peptide markers of diabetic nephropathy in humans to generate a classifier composed of 21 ortholog peptides. This classifier predicted the response to disease and treatment with inhibitors of the renin-angiotensin system in mice. The humanized classifier was significantly correlated with glomerular lesions. Using a human type 2 diabetic validation cohort of 207 patients, the classifier also distinguished between patients with and without diabetic nephropathy, and their response to renin-angiotensin system inhibition. Thus, a combination of multiple molecular features common to both human and murine disease could provide a significant change in translational drug discovery research in type 2 diabetic nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Klein J,Ramirez-Torres A,Ericsson A,Huang Y,Breuil B,Siwy J,Mischak H,Peng XR,Bascands JL,Schanstra JPdoi
10.1016/j.kint.2016.06.023subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1045-1055issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30313-1journal_volume
90pub_type
杂志文章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：:Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Dep...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.42
更新日期：2011-06-01 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：:Vascular calcification (VC) is an important reason for the high burden of vascular disease among chronic dialysis patients. Chronic kidney disease (CKD) is associated with increased promoters and decreased inhibitors of VC. The circulating levels of fetuin-A, a well-described inhibitor of calcification, regulate the c...
journal_title：Kidney international
pub_type： 评论,杂志文章,评审
doi：10.1038/sj.ki.5002355
更新日期：2007-07-01 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：:Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.05.007
更新日期：2019-10-01 00:00:00
abstract：:Current practice recommends metabolic evaluation of patients who have formed multiple renal stones, but not those with one stone or temporally remote stones. This presumes that recentness and recurrence imply greater risk of new future stones. We hypothesize that number of stones reflects how long patients are permitt...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.224
更新日期：1994-06-01 00:00:00
abstract：:The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL pla...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/ki.1997.221
更新日期：1997-05-01 00:00:00
abstract：:The OSCAR study was a multicenter, prospective randomized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker (ARB) uptitration to an ARB plus calcium channel blocker (CCB) combination. In this prospective study, we performed presp...
journal_title：Kidney international
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/ki.2012.326
更新日期：2013-01-01 00:00:00
abstract：:We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second pha...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1997.442
更新日期：1997-11-01 00:00:00
abstract：:The present studies were undertaken to assess the effects of 5'-N-ethylcarboxamideadenosine (NECA), an adenosine analogue, on erythropoietin (Epo) production. NECA (0.05 and 0.1 mumol/kg i.v.) produced significant increases in serum Epo levels (368.8 +/- 56.1 and 384.6 +/- 45.9 mU/ml, respectively) in exhypoxic polycy...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1993.307
更新日期：1993-10-01 00:00:00
abstract：BACKGROUND:alpha 2 Macroglobulin (alpha 2M), a protease inhibitor, is often increased in plasma of patients with the nephrotic syndrome. Although it has been speculated that synthesis is increased, no direct measurements have been performed. METHODS:alpha 2M synthesis in both normal subjects (N = 4) and nephrotic pati...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00018.x
更新日期：1998-08-01 00:00:00
abstract：:Mitochondria are critical in determining a cell's energy homeostasis and fate, and mitochondrial dysfunction has been implicated in the pathogenesis of chronic kidney disease (CKD). We sought to identify causative mitochondrial microRNAs. A microarray screen of kidney tissue from healthy mice identified 97 microRNAs t...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2018.12.028
更新日期：2019-06-01 00:00:00
abstract：:Hyperlipidemia can induce or aggravate renal tubulointerstitial injury. Experiments in a complex rat model with chronic glomerulonephritis and long-standing, coexisting hyperlipidemia suggested that induction of xanthine oxidase (XO), with increased oxygen radical generation, is involved in aggravation of tubulointers...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000121
更新日期：2006-02-01 00:00:00
abstract：BACKGROUND:Gap junctional intercellular communication (GJIC) plays an important role in the regulation of cell growth, migration, and differentiation. Ultrastructural and histochemical studies indicate the existence of a high density of gap junctions among mesangial cells (MCs), but little is known about their regulati...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2000.00041.x
更新日期：2000-05-01 00:00:00
abstract：:To analyze the role of clusterin in renal diseases involving a regenerative process, we have used a novel rodent model to compare temporal and spatial expression of clusterin mRNA. Thus, renal artery stenosis was used to induce unilateral non-infarctive renal atrophy. After several weeks, when cellular pathology of at...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1995.54
更新日期：1995-02-01 00:00:00
abstract：:We have analyzed the protein content of proximal tubular fluid (PTF) by ultramicro disc electrophoresis and measured total protein excretion rates both in control conditions and during angiotensin infusion to the rat. Under control conditions PTF albumin concentration was 1.49 +/- 1.12 (SD) mg/100 ml and did not incre...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1975.83
更新日期：1975-08-01 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：:These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.121
更新日期：1992-04-01 00:00:00
abstract：:Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-induc...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2017.03.010
更新日期：2017-08-01 00:00:00
abstract：:Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the b...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.91
更新日期：2009-07-01 00:00:00
abstract：:Progression of diabetic nephropathy appears directly related to renal tubulointerstitial injury, but the involved genes are incompletely delineated. To identify such genes, DNA microarray analysis was performed with RNA from renal proximal tubules (RPTs) of streptozotocin-induced diabetic Wistar rats, spontaneously di...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000206
更新日期：2006-03-01 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：:When the endotoxin-lipopolysaccharide (LPS) derived from the cell wall of gram-negative bacteria is given to the rat in vivo, there are prompt, marked decreases in glomerular filtration rate (GFR), renal blood flow (RBF) and % Na+ reabsorption (%T-Na+). However, it has not been determined whether the endotoxin itself ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.105
更新日期：1990-05-01 00:00:00
abstract：BACKGROUND:The purpose of this study was to evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultrahigh doses of irbesartan in type 2 diabetic patients with microalbuminuria. METHODS:This double-masked randomized crossover trial included 52 (41 males) hypertensive type 2 diabetic ...
journal_title：Kidney international
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1523-1755.2005.00511.x
更新日期：2005-09-01 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：:Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended t...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1111/j.1523-1755.2004.66001.x
更新日期：2004-12-01 00:00:00
abstract：:The impacts of IgA nephropathy and pregnancy on each other were evaluated in 118 women who conceived 168 times between 1970 and 1988. Rates of spontaneous abortion, normal delivery, live birth and perinatal death were 9, 66, 87 and 4%, respectively. Infants born to women with glomerular filtration rates (GFR) lower th...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.320
更新日期：1991-12-01 00:00:00
abstract：:Mesangial cells are known to secrete metalloproteinases that are capable of degrading the constituents of the GBM, and hence are potentially involved not only in the regular maintenance of the ECM components in the glomerulus, but also of contributing to any damage to these components that occurs in disease states. In...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.345
更新日期：1994-09-01 00:00:00
abstract：:Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 wee...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.283
更新日期：1990-11-01 00:00:00
