Abstract:
BACKGROUND:The p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 mRNA is induced in murine kidney after several types of acute renal failure, including cisplatin administration, ischemia-reperfusion, and ureteral obstruction. We reported that after cisplatin injection, mice with a p21 gene deletion developed much more severe renal damage than wild-type mice. To dissociate the effects of cisplatin-induced DNA damage and subsequent initiation of DNA damage-dependent cell death pathways from effects of acute renal failure, we have now examined mice after ischemia-reperfusion, a model of renal failure not associated with genotoxin-induced DNA damage early after the injury. METHODS:Wild-type and p21(-/-) mice were made ischemic by clamping both renal hila for 30 or 50 minutes. At various times after reflow, mortality and parameters of renal function and morphology were quantified. Also, the nuclear proteins p21 and proliferating cell nuclear antigen (PCNA) were localized in kidney sections by immunohistochemistry. RESULTS:Kidney function was more impaired and mortality increased significantly in p21(-/-) mice as compared with p21(+/+) mice. We found more cell cycle activity, indicated by increased number of mitotic cells and nuclear PCNA-positive cells, in kidney of p21(-/-) mice. CONCLUSIONS:In this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Megyesi J,Andrade L,Vieira JM Jr,Safirstein RL,Price PMdoi
10.1046/j.1523-1755.2001.00044.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
2164-72issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48109-8journal_volume
60pub_type
杂志文章abstract:BACKGROUND:Fabry disease is an X-linked generalized progressive debilitating lysosomal storage disorder. The disease usually manifests in childhood, but the diagnosis is often made following the occurrence of late-stage complications such as progressive kidney failure. In order to identify key novel renal diagnostic im...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00846.x
更新日期:2004-09-01 00:00:00
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 par...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.06.023
更新日期:2016-11-01 00:00:00
abstract::Hypertension is associated with an accelerated rate of decline in renal function in patients with chronic renal disease. To identify factors that might alter the rate of decline in renal function, we reviewed records of 200 patients from the Nephrology Clinic of the Durham VA Medical Center who had chronic progressive...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.93
更新日期:1990-04-01 00:00:00
abstract::Using in situ hybridization and immunocytochemistry we describe the renal localization of the PDGF alpha-receptor. PDGF alpha-receptor mRNA was uniformly present in human metanephric kidney in interstitial cells and vascular arcades that course through the blastema. PDGF alpha-receptor mRNA was present in some mesangi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.157
更新日期:1997-04-01 00:00:00
abstract::In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal he...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.kint.2018.08.031
更新日期:2018-12-01 00:00:00
abstract::Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.029
更新日期:2020-06-01 00:00:00
abstract::The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.141
更新日期:1981-09-01 00:00:00
abstract:BACKGROUND:Carriers of autosomal-recessive and X-linked Alport syndrome often have a thinned glomerular basement membrane (GBM) and have mutations in the COL4A3/COL4A4 and COL4A5 genes respectively. Recently, we have shown that many individuals with thin basement membrane disease (TBMD) are also from families where hem...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002480.x
更新日期:2001-08-01 00:00:00
abstract::Mineralocorticoid hormones stimulate Na+ absorption and K+ secretion by the cortical collecting tubule. There is good evidence that this stimulation involves increasing luminal membrane Na+ permeability and the turnover rate (or number) of the Na+-K+ pumps. These experiments were designed to examine whether mineraloco...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.177
更新日期:1985-10-01 00:00:00
abstract::Extracellular fluid volume expansion is known to produce exaggerated natriuresis in essential hypertension. In order to assess the role of hemodynamic and intrarenal physical factors upon natriuretic response to central volume expansion, two hour water immersion (WI) experiments were made in six uncomplicated essentia...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.79
更新日期:1988-04-01 00:00:00
abstract::A genome-wide association study (GWAS) indicated that myeloperoxidase-ANCA associated vasculitis (AAV) is associated with HLA-DQ. However, susceptibility alleles in these loci have been under-investigated. Here we genotyped 258 Chinese patients with myeloperoxidase-AAV and 597 healthy control individuals at HLA DRB1, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.06.015
更新日期:2019-10-01 00:00:00
abstract::Experimental studies have demonstrated the cardinal role played by the mononuclear phagocyte system in the removal of antigen-antibody complexes. To assess the functional capacity of phagocytes in patients with renal disease, 33 normal subjects, 10 patients with mesangial proliferative glomerulonephritis, 8 patients w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.105
更新日期:1983-06-01 00:00:00
abstract::Fibroblast growth factors (FGFs) regulate cell proliferation and differentiation, and are also important regulators of extracellular matrix. They are among the most potent angiogenic factors known. Evidence suggests the FGFs play a role in glomerular development and pathology. The aim of the present study was to deter...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.238
更新日期:1997-06-01 00:00:00
abstract::Problems with vascular access are an important cause of morbidity and mortality in hemodialysis patients. We established a rodent model of arteriovenous fistula by anastomosing the end of a lateral vein to the side of the ventral artery of the rat tail. All operations were technically successful and in all animals the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.207
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Nephrologists report that patients' choice should play an important role in the selection of renal replacement therapy (RRT) for end-stage renal disease (ESRD). In the United States, kidney transplant rates remain low and <10% of patients utilize home dialysis therapies. This study examined the effect of pre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00453.x
更新日期:2005-07-01 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::Despite the increasing knowledge of the role of gangliosides in normal and diseased tissues, little is known of the presence, distribution and functions of these molecules in the kidney. In this study we analyzed the main gangliosides of isolated glomeruli and cortical, medullary and papillary fractions of the human, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.14
更新日期:1994-01-01 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::Systemic AA type amyloidosis with renal involvement is the major cause of morbidity and mortality in patients with familial Mediterranean fever (FMF). A histopathological examination is essential to achieve a definite diagnosis in systemic amyloidosis. The diagnostic yield of the procedure varies according to the biop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.318
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:While the progression of renal disease to end stage is strongly correlated with tubulointerstitial changes, the control of the fibrotic process within the interstitium is poorly understood. Basic fibroblast growth factor (FGF-2) has been implicated as a major growth factor involved in fibroblast activation a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00723.x
更新日期:2001-06-01 00:00:00
abstract::Nephronophthisis is an autosomal recessive chronic tubulointerstitial disease that progresses to end-stage renal disease (ESRD) in about 10% of cases during infancy. Mutations in the INVS (NPHP2) gene were found in a few patients with infantile nephronophthisis. Mutations of NPHP3, known to be associated with adolesce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.662
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Home nocturnal hemodialysis is an intensive form of hemodialysis, where patients perform their treatments at home for about 7 hours approximately 6 nights a week. Compared with in-center conventional hemodialysis, home nocturnal hemodialysis has been shown to improve physiologic parameters and reduce health ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00157.x
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transpla...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2004.00919.x
更新日期:2004-10-01 00:00:00
abstract::Enalapril effectively decreases hematocrits in patients with postrenal transplant erythrocytosis (PTE). We studied the effect of enalapril withdrawal on erythropoiesis in 18 patients with PTE who had been treated for 13 +/- 8 months. Hematocrit, reticulocyte count, plasma erythropoietin, and plasma insulin-like growth...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.411
更新日期:1994-11-01 00:00:00
abstract::We previously demonstrated that urinary endothelin excretion is increased in rats with extensive renal mass reduction, a model of progressive renal disease. Here we explored whether the increased urinary endothelin in this model were due to induction of renal pre-pro-endothelin-1 gene and whether changes in endothelin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.53
更新日期:1993-02-01 00:00:00
abstract::We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a signific...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.267
更新日期:1987-11-01 00:00:00
abstract::International clinical practice guidelines for the management of anemia in chronic kidney disease suggest target hemoglobin levels ≤ 11.5 g/dl (115 g/l), with individualized consideration of slightly higher hemoglobin targets to improve quality of life. An updated meta-analysis of randomized trials demonstrates no sig...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.03.001
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:The renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta HSD2) enzyme inactivates 11-hydroxy steroids in the kidney, thereby protecting the nonselective mineralocorticoid (MR) receptor from occupation by glucocorticoids. Loss-of-function mutations in the gene encoding 11beta HSD2 (HSD11B2) result in over...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67119.x
更新日期:2005-02-01 00:00:00
abstract::We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.100
更新日期:2015-09-01 00:00:00
abstract::The role of glutathione (GSH) in the preservation of renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.142
更新日期:1983-08-01 00:00:00