Abstract:
:Complement factor 5a (C5a) interaction with its receptor (C5aR1) contributes to the pathogenesis of inflammatory diseases, including acute kidney injury. However, its role in chronic inflammation, particularly in pathogen-associated disorders, is largely unknown. Here we tested whether the development of chronic inflammation and renal fibrosis is dependent on C5aR1 in a murine model of chronic pyelonephritis. C5aR1-deficient (C5aR1-/-) mice showed a significant reduction in bacterial load, tubule injury and tubulointerstitial fibrosis in the kidneys following infection, compared with C5aR1-sufficient mice. This was associated with reduced renal leukocyte infiltration specifically for the population of Ly6Chi proinflammatory monocytes/macrophages and reduced intrarenal gene expression of key proinflammatory and profibrogenic factors in C5aR1-/- mice following infection. Antagonizing C5aR1 decreased renal bacterial load, tissue inflammation and tubulointerstitial fibrosis. Ex vivo and in vitro studies showed that under infection conditions, C5a/C5aR1 interaction upregulated the production of proinflammatory and profibrogenic factors by renal tubular epithelial cells and monocytes/macrophages, whereas the phagocytic function of monocytes/macrophages was down-regulated. Thus, C5aR1-dependent bacterial colonization of the tubular epithelium, C5a/C5aR1-mediated upregulation of local inflammatory responses to uropathogenic E. coli and impairment of phagocytic function of phagocytes contribute to persistent bacterial colonization of the kidney, chronic renal inflammation and subsequent tubulointerstitial fibrosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Choudhry N,Li K,Zhang T,Wu KY,Song Y,Farrar CA,Wang N,Liu CF,Peng Q,Wu W,Sacks SH,Zhou Wdoi
10.1016/j.kint.2016.04.023subject
Has Abstractpub_date
2016-09-01 00:00:00pages
540-54issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30197-1journal_volume
90pub_type
杂志文章abstract::Efficacy and safety of antibiotic 'locks', in prevention of thrombotic and infectious complication-related morbidity and mortality, among diabetics dialyzed through tunneled-cuffed catheters (TCCs) has not been effectively investigated. This trial was designed to investigate the outcome of TCCs (n = 109), inserted amo...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001776
更新日期:2006-11-01 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::Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) dai...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.93
更新日期:1975-09-01 00:00:00
abstract::In male Wistar rats, renal adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were measured by 31phosphorus nuclear magnetic resonance (31P NMR) and correlated with renal function before, during, and for one hour after a period of 30 to 40 minutes hemorrhagic hypotension. In animals which suff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.192
更新日期:1986-09-01 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::Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.236
更新日期:2014-10-01 00:00:00
abstract::Protein energy wasting is a common feature of patients with chronic kidney disease (CKD) and is associated with poor outcomes. Protein energy wasting and cachexia, a severe form of protein energy wasting, are characterized by increased resting energy expenditure but the underlying mechanisms are unclear. Browning corr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.03.027
更新日期:2020-09-01 00:00:00
abstract::We describe a rat model of renal failure that separates catabolic and anabolic states from each other. Muscle protein synthesis was compared during the anabolic period between sham (S) operated and renal failure (RF) rats that were fed different levels of dietary protein. Male rats weighing between 60 and 80 g first h...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.104
更新日期:1991-05-01 00:00:00
abstract::In summary, it is evident that malnutrition is highly prevalent in ESRD patients. This is clearly related to multiple factors encountered during the pre-dialysis stage, as well as during maintenance dialysis therapy. A body of evidence highlights the existence of relationship between malnutrition and outcome in this p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.323
更新日期:1996-08-01 00:00:00
abstract::Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.035
更新日期:2020-06-01 00:00:00
abstract::Pathogenesis of vascular calcification in chronic kidney disease. Background. Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the pro...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00421.x
更新日期:2005-08-01 00:00:00
abstract::We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intak...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.295
更新日期:1990-11-01 00:00:00
abstract::There is a paucity of studies describing malignancy-related mortality after kidney transplantation. To help quantify this, we extracted data for all kidney-alone transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.458
更新日期:2014-06-01 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: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: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::Albumin is an acceptor of lysophosphatidylcholine (LPC), product of the lecithin:cholesterol acyl transferase (LCAT) reaction, and it has been suggested that low LCAT activity and reduced cholesterol esterification rate in patients with the nephrotic syndrome may be linked to depletion of albumin. Effects of low plasm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.248
更新日期:1994-07-01 00:00:00
abstract::The impact of pediatric chronic kidney disease (CKD) on acquisition of volumetric bone mineral density (BMD) and cortical dimensions is lacking. To address this issue, we obtained tibia quantitative computed tomography scans from 103 patients aged 5-21 years with CKD (26 on dialysis) at baseline and 12 months later. G...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.347
更新日期:2013-03-01 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:BACKGROUND:The renin-angiotensin system has been known to regulate blood pressure and body fluid homeostasis. Several lines of evidence have shown that renin gene expression and release are up-regulated by beta-adrenergic stimulation, sodium depletion, and angiotensin converting enzyme inhibition, but down-regulated by...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00209.x
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:Recent advances in the understanding of the molecular biology of rodent renal development have lead to the ability to culture the components of the developing rat kidney-the ureteric bud (UB) and the metanephric mesenchyme (MM)-in isolation from one another. Here we here describe a method for subculturing an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00694.x
更新日期:2002-12-01 00:00:00
abstract::In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resista...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.321
更新日期:1991-12-01 00:00:00
abstract:BACKGROUND:Cux-1 is a murine homeodomain protein that functions as a cell cycle-dependent transcriptional repressor in proliferating cells. Targets of Cux-1 repression include the cyclin kinase inhibitors p21 and p27. In the kidney, Cux-1 is spatially and temporally regulated, and ectopic expression of Cux-1 in transge...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67099.x
更新日期:2005-02-01 00:00:00
abstract::Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.12.013
更新日期:2020-12-22 00:00:00
abstract::The parathyroid hormone (PTH) response to hypocalcemia was studied in 18 hemodialysis patients with osteitis fibrosa, and the relationship with PTH and bone histology in 26 hemodialysis patients. Hypocalcemia was produced during hemodialysis by the use of a dialysate devoid of calcium. Both amino (N) (P less than 0.05...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.37
更新日期:1984-02-01 00:00:00
abstract::The X-linked Hyp and Gy mutations are murine homologues of X-linked hypophosphatemia (XLH), a dominant disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets, hypophosphatemia and decreased renal tubular maximum for Pi reabsorption relative to glomerular filtration rate (Tmp/GFR). In Hyp a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.149
更新日期:1996-04-01 00:00:00
abstract::While it is known that risk of death from sepsis is higher in patients with pre-existing chronic kidney disease its mechanism is unknown. To study this we established a two-stage mouse model where renal disease was first induced by folic acid injection followed by sub-lethal cecal ligation and puncture to induce sepsi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.346
更新日期:2008-10-01 00:00:00
abstract::Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 pro...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001630
更新日期:2006-08-01 00:00:00
abstract::Undecalcified sections of doubly tetracycline-labeled transiliac bone biopsy specimens obtained from ten hemodialyzed patients before and 10 to 16 months after parathyroidectomy (PTX) were analyzed. Before parathyroidectomy (total PTX with autotransplant in six patients and subtotal PTX in four patients), all the pati...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1985.27
更新日期:1985-02-01 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