Abstract:
UNLABELLED:Expression of apoptosis regulatory genes in chronic cyclosporine nephrotoxicity favors apoptosis. BACKGROUND:Chronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis, tubular dropout, and loss of cellularity in areas of fibrosis. Apoptosis was found to play a role in CsA-induced fibrosis. We evaluated the role of the death genes p53, Bax, and Fas-L (ligand), survival gene Bcl-2, interleukin-converting enzyme (ICE), and caspase-3. METHODS:Salt-depleted rats were administered CsA 15 mg/kg/day or vehicle (VH) and were sacrificed at 7 or 28 days. Apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling assay. p53 and Bax expressions were evaluated by Northern and Western blot analysis. Fas-L and Bcl-2 expressions were evaluated by immunofluorescence. In addition to ICE mRNA, caspase-3 enzymatic activity was assayed. RESULTS:Although no differences were seen at one week, apoptosis-positive cells increased with CsA at four weeks (P < 0.05) and correlated with tubular atrophy and interstitial fibrosis (r = 0.8, P < 0.05). CsA induced the expression of p53 (P < 0.05) and Bax (P < 0.01) and decreased that of Bcl-2 (P < 0.05). CsA up-regulated Fas-L expression (P < 0.001). ICE mRNA and caspase-3 activity were also increased (P < 0.01). The changes occurred as early as one week and remained statistically significant at four weeks. CONCLUSIONS:Specific apoptotic genes are increased in chronic CsA nephrotoxicity. The balance favors the induction of apoptosis. Increased apoptosis could explain the tubular dropout and loss of cellularity with fibrosis. This then may impair the ability of the tubulointerstitium to remodel. Apoptosis could also contribute to some of CsA immunosuppressive effects on activated lymphocytes.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Shihab FS,Andoh TF,Tanner AM,Yi H,Bennett WMdoi
10.1046/j.1523-1755.1999.00794.xsubject
Has Abstractpub_date
1999-12-01 00:00:00pages
2147-59issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46551-2journal_volume
56pub_type
杂志文章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:BACKGROUND:Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. The chromosomal locus for MCKD2 was localized on chromosome 16p12. Within this chromosomal region...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00269.x
更新日期:2003-11-01 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 present studies address the metabolic processes that support the reabsorption of sodium and the secretion of bicarbonate in the interspersed but distinct principal and intercalated cells of the cortical collecting duct (CCD). In microperfused rabbit CCD, sodium reabsorption was measured by lumen-to-bath 22Na flux,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00754.x
更新日期:1998-02-01 00:00:00
abstract:BACKGROUND:To chart the epidemiology of primary glomerular disease by means of a prospective regional study in the southern part of The Netherlands. METHODS:Experienced renal technicians collected renal biopsies, blood, and 24-hour urine samples at the bed site in each of the participating hospitals. The material was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00835.x
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00203.x
更新日期:2003-10-01 00:00:00
abstract::The cellular redox state is altered in a number of pathological conditions, including various forms of glomerular injury and diabetes. For example, glucose, via the pentose phosphate pathway generates NADPH, which maintains glutathione (GSH) (part of a major intracellular reducing system) in its reduced state. GSH in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.286
更新日期:1994-08-01 00:00:00
abstract::Acute kidney injury (AKI) severe enough to require dialysis is increasing and associated with high mortality, yet robust information about temporal epidemiology of AKI requiring dialysis in England is lacking. In this retrospective observational study of the Hospital Episode Statistics (HES) data set covering the enti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.234
更新日期:2015-11-01 00:00:00
abstract::Quartan malarial infection causes an immune complex nephritis in some individuals, which, once established, is sustained by mechanisms not yet fully explained, but which probably involve autoimmune processes. The presenting clinical and biochemical findings of the quartan malarial nephrotic syndrome are similar to tho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.103
更新日期:1979-07-01 00:00:00
abstract::We have sought to determine the mechanisms driving fluid secretion by the cystic epithelium in autosomal dominant polycystic kidney disease (ADPKD). We have performed in vitro experiments on intact cysts dissected from discarded ADPKD kidneys, on monolayers of cells cultured from the cystic epithelium and on microcyst...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.230
更新日期:1996-06-01 00:00:00
abstract::Polycystic kidney disease progresses more rapidly in men than in women. To investigate the basis for this sexual dimorphism, we exposed Madin-Darby canine kidney (MDCK) cells grown on collagen-coated cell culture inserts to control media, or to estradiol or testosterone (1 nM-1 microM). Compared to control and estradi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.211
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS:Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00406.x
更新日期:2005-07-01 00:00:00
abstract::The subcellular distribution of immunoreactive kallikrein was described in the rat nephron using ultrastructural immunocytochemistry. The renal tissue was fixed with a mixture of buffered picric acid-paraformaldehyde-glutaraldehyde and immunostained with the peroxidase-antiperoxidase method for the electron microscope...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.115
更新日期:1985-07-01 00:00:00
abstract::Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-β-synthas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.449
更新日期:2014-06-01 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::Tubular atrophy and interstitial fibrosis, important in progression of renal diseases, including diabetic (D) and cyclosporine-induced (CSA) nephropathy, have been considered irreversible. Normoglycemia for 10 years following pancreas transplantation alone (PTA) reversed D glomerulopathy lesions. This study quantified...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000153
更新日期:2006-03-01 00:00:00
abstract::Membranous nephropathy is characterized by deposition of immune complexes along the glomerular basement membrane. PLA2R and THSD7A are target antigens in 70% and 1-5% of primary membranous nephropathy cases, respectively. In the remaining cases, the target antigen is unknown. Here, laser microdissection of glomeruli f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.09.014
更新日期:2020-01-01 00:00:00
abstract::In recent years, a substantial body of experimental and clinical work has been devoted to C3 glomerulopathy and Ig-mediated membranoproliferative glomerulonephritis. Despite the rapid accumulation of data, several uncertainties about these 2 rare forms of nephropathies persist. They concern their pathophysiology, clas...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2020.05.053
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:The superiority of renin-angiotensin system (RAS) blockade in providing renoprotection has been attributed to class-specific blood pressure "(BP)-independent" mechanisms. However, the conventional BP measurement methodology on which such conclusions are based is inherently limited for an accurate assessment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00009.x
更新日期:2000-04-01 00:00:00
abstract::The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and their formation is conditioned by specific stone-forming pathophysiologies. We performed intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate (CaOx), intestinal by...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000238
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Epithelial cells in the renal inner medulla accumulate osmolytes such as betaine to maintain normal cell volume during prolonged extracellular hypertonic stress. Betaine accumulation is the result of activation of transcription of the BGT1 transporter gene followed by increased betaine transport. METHODS:We...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00733.x
更新日期:2001-06-01 00:00:00
abstract::We have assessed the bone histology in 259 chronic dialysis patients, all of whom were in the same dialysis program. All patients had bone biopsies with quantitative histomorphometry, intact parathyroid hormone (PTH) measurements, basal and deferoxamine stimulated serum aluminum levels. Results demonstrate the increas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.64
更新日期:1993-02-01 00:00:00
abstract::We have previously identified the engulfment and cell motility 1 (ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001939
更新日期:2006-11-01 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::Unilateral ureteral obstruction results in marked changes in renal function throughout the nephron, including impaired acid and potassium secretion and salt wastage. The nephron site believed responsible for the acidification defect is the collecting duct. It has been presumed, although not demonstrated, that the cell...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.11
更新日期:1990-01-01 00:00:00
abstract::The impact of high-flux hemodialysis on clinical outcomes remains controversial. We have previously shown that in vivo transmigrated leukocytes from patients with low-flux bioincompatible hemodialysis have an impaired capacity to upregulate CD11b at the site of interstitial inflammation. In the present study, we inves...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002090
更新日期:2007-03-01 00:00:00
abstract::In this study, we have evaluated 50 children (30 girls and 20 boys; mean age, 10.1 years) with a variety of renal diseases in whom renal biopsy specimens showed crescents in greater than or equal to 50% of glomeruli. Initial clinical features included edema in 61%; hypertension in 51%; gross hematuria in 73%; 3 to 4+ ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.30
更新日期:1985-02-01 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::Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF-beta, a cytokine implicated in the pathogenesis of tubulointerstitial fibrosis. We examined the expression of thromb...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00774.x
更新日期:1998-02-01 00:00:00
abstract:BACKGROUND:Aquaporin-2 (AQP-2) proteins are mainly expressed at the apical region of the collecting duct cells. We previously reported three different mutations in the C-terminus of AQP-2 that all-cause autosomal-dominant nephrogenic diabetes insipidus. When one of these mutant AQP-2s was expressed in Madin-Darby canin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00654.x
更新日期:2005-11-01 00:00:00