Abstract：
:Chronic kidney disease (CKD) remains one of the leading causes of death in the developed world, and acute kidney injury (AKI) is now recognized as a major risk factor in its development. Understanding the factors leading to CKD after acute injury are limited by current animal models of AKI, which concurrently target various kidney cell types including epithelial, endothelial, and inflammatory cells. Here, we developed a mouse model of kidney injury using the Six2-Cre-LoxP technology to selectively activate expression of the simian diphtheria toxin (DT) receptor in renal epithelia derived from the metanephric mesenchyme. By adjusting the timing and dose of DT, a highly selective model of tubular injury was created to define the acute and chronic consequences of isolated epithelial injury. The DT-induced sublethal tubular epithelial injury was confined to the S1 and S2 segments of the proximal tubule rather than being widespread in the metanephric mesenchyme-derived epithelial lineage. Acute injury was promptly followed by inflammatory cell infiltration and robust tubular cell proliferation, leading to complete recovery after a single toxin insult. In striking contrast, three insults to renal epithelial cells at 1-week intervals resulted in maladaptive repair with interstitial capillary loss, fibrosis, and glomerulosclerosis, which was highly correlated with the degree of interstitial fibrosis. Thus, selective epithelial injury can drive the formation of interstitial fibrosis, capillary rarefaction, and potentially glomerulosclerosis, substantiating a direct role for damaged tubule epithelium in the pathogenesis of CKD.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Grgic I,Campanholle G,Bijol V,Wang C,Sabbisetti VS,Ichimura T,Humphreys BD,Bonventre JVdoi
10.1038/ki.2012.20subject
Has Abstractpub_date
2012-07-01 00:00:00pages
172-83issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55520-8journal_volume
82pub_type
杂志文章abstract：:In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.312
更新日期：1989-12-01 00:00:00
abstract：BACKGROUND:Previous reports have shown the presence of erythrogenic toxin type B (ETB), apoptosis, proliferation, and leukocyte infiltration in biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). METHODS:Attempting to correlate the apoptotic and proliferative events with the interaction of ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.059003950.x
更新日期：2001-03-01 00:00:00
abstract：:Fibroblasts in parenchymal organs potentially contribute extracellular matrix to local fibrogenic processes. This contribution, in some circumstances, may be initiated by cytokines disseminated from inflammatory lesions. Different populations of fibroblasts, however, might respond distinctively to this cytokine bath d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.3
更新日期：1992-01-01 00:00:00
abstract：:Class II gene products of the major histocompatibility complex (MHC) are not expressed usually in abundance on normal epithelium. The cell surface visibility of such proteins for the immune system is thought to be limited protectively in order to minimize inflammation consequent to the recognition of self-antigens in ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.191
更新日期：1991-07-01 00:00:00
abstract：:In his hypothesis of the evolution of renal functions Homer Smith proposed that the formation of glomerular nephron and body armor had been adequate for the appearance of primitive vertebrates in fresh water and that the adaptation of homoiotherms to terrestrial life was accompanied by the appearance of the loop of He...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1996.220
更新日期：1996-06-01 00:00:00
abstract：BACKGROUND:Acute renal failure (ARF) has a high morbidity and mortality. Many therapies have worked in animals but were unsuccessful in clinical trials. The inability to diagnose ARF early may have impaired the success of these trials. METHOD:We screened a subtraction library to search for potential disease markers th...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00633.x
更新日期：2002-11-01 00:00:00
abstract：UNLABELLED:Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. BACKGROUND:In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcit...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1523-1755.2000.00819.x
更新日期：2000-01-01 00:00:00
abstract：BACKGROUND:Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced exclusively by cells of the thick ascending limb of Henle's loop (TALH). This study examined whether dietary salt altered renal THP production. METHODS:Male Sprague-Dawley rats were examined on days 1, 4, and 15 following placement in met...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00117.x
更新日期：1998-10-01 00:00:00
abstract：:The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.31
更新日期：1991-02-01 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：:To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.289
更新日期：2009-10-01 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：:Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-ac...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.75
更新日期：1991-04-01 00:00:00
abstract：:Ambulatory blood pressure monitoring (ABPM) remains a reference standard, but the minimal number of ABPM readings required to diagnose hypertension has not been empirically validated. Among 360 patients with chronic kidney disease and 38 healthy controls, 24-hour blood pressure was recorded 2 times per hour during the...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2018.08.021
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:To identify susceptibility genes for diabetic nephropathy, GeneChip Expression Analysis was employed to survey the gene expression profile of diabetic KK/Ta mouse kidneys. METHODS:Kidneys from three KK/Ta and two BALB/c mice at 20 weeks of age were dissected. Total RNA was extracted and labeled for hybridiz...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00312.x
更新日期：2003-12-01 00:00:00
abstract：:Methods for estimating glomerular volume were compared in Zenker-fixed, paraffin-embedded biopsies from 10 patients with insulin-dependent diabetes mellitus and 6 normal kidney donors. Two methods of measurement of individual glomerular volumes were used: the Cavalieri method (considered the "gold standard") and the m...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.165
更新日期：1992-04-01 00:00:00
abstract：BACKGROUND:Several examinations have been performed to identify the genes involved in chronic renal failure using 5/6 nephrectomized rats. Recently, many systematic techniques for examining molecular expression have been developed. They might also be effective in elucidating the molecular mechanism of progressive renal...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2004.00704.x
更新日期：2004-07-01 00:00:00
abstract：BACKGROUND:Adrenomedullin (ADM) exerts antiproliferative effects on rat mesangial cells in vitro and, therefore is a possible renoprotective agent. In contrast, nitric oxide (NO) is capable of exerting both cytoprotective and cytotoxic actions. It was the objective of the present study to examine whether NO stimulates ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00330.x
更新日期：2002-05-01 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：:The introduction of two-photon microscopy, along with the development of new fluorescent probes and innovative computer software, has advanced the study of intracellular and intercellular processes in the tissues of living organisms. Researchers can now determine the distribution, behavior, and interactions of labeled...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/sj.ki.5002315
更新日期：2007-08-01 00:00:00
abstract：:A genome-wide association scan of the Genetics of Kidneys in Diabetes (GoKinD) collections identified four novel susceptibility loci, located on chromosomes 7p14.3, 9q21.32, 11p15.4, and 13q33.3 associated with type 1 diabetic nephropathy. A recent evaluation of these loci in Japanese patients with type 2 diabetes sup...
journal_title：Kidney international
pub_type： 杂志文章,meta分析
doi：10.1038/ki.2011.64
更新日期：2011-07-01 00:00:00
abstract：:In previous studies from this laboratory it has been shown that ATP-ase activity in situ in the glomerular basement membrane (GBM) is clearly reduced in rats rendered nephrotic after treatment with adriamycin (ADR). The question was raised whether this reduction of ATP-ase activity in the GBM is due to toxic activity ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1987.55
更新日期：1987-03-01 00:00:00
abstract：:As new components of the renin-angiotensin system (RAS) are elucidated, our understanding of the complexities of their interactions also advances. Previous studies have determined that podocytes possess a local RAS that can generate angiotensin II. Podocytes have also been shown to express angiotensin-converting enzym...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2012.127
更新日期：2012-08-01 00:00:00
abstract：:Administration of antibody, directed against glomerular basement membrane (GBM) heparan sulfate-proteoglycan, into a presensitized rat results in the induction of membranous nephropathy with subepithelial immune-complex deposits. In this investigation, we examined the mechanisms responsible for the formation of subepi...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1988.166
更新日期：1988-08-01 00:00:00
abstract：:Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rh...
journal_title：Kidney international
pub_type： 杂志文章,多中心研究
doi：10.1016/j.kint.2017.11.019
更新日期：2018-04-01 00:00:00
abstract：:Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, the...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1988.58
更新日期：1988-03-01 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：BACKGROUND:The detailed mechanisms of glucocorticoid action in idiopathic nephrotic syndrome and progressive glomerulonephritides have not been clearly elucidated. The pharmacological actions of glucocorticoids are mediated by their binding to an intracellular protein, the glucocorticoid receptor (GR). The determinatio...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00503.x
更新日期：1999-07-01 00:00:00
abstract：BACKGROUND:Transplantation of developing metanephroi into adult hosts has been proposed as a means to augment host renal function. METHODS:We implanted whole metanephroi from embryonic day 15 (E15) rats subcapsularly in kidneys or into the omentum of non-immunosupressed adult rat hosts. At the time of implantation, so...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00971.x
更新日期：1998-07-01 00:00:00
abstract：:The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjecte...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1995.230
更新日期：1995-06-01 00:00:00
