Abstract:
BACKGROUND:Chronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis and afferent arteriolar hyalinosis. L-arginine (L-Arg), the substrate for nitric oxide (NO) synthase and N-nitro-L-arginine-methyl ester (L-NAME), the NO synthase inhibitor, were shown to modulate acute CsA nephrotoxicity. However, the mechanism of fibrosis in chronic CsA nephrotoxicity remains unclear. Thus, we examined the effect of NO modulation on fibrosis and the expression of transforming growth factor-beta1 (TGF-beta1) and matrix proteins in chronic CsA nephrotoxicity. METHODS:Rats were administered CsA (7.5 mg/kg), CsA + L-Arg (1.7 g/kg), CsA + L-NAME (3.5 mg/kg), vehicle (VH), VH + L-Arg, and VH + L-NAME, and were sacrificed at 7 or 28 days. NO production, physiologic parameters, and histology were studied in addition to the mRNA expression of TGF-beta1, plasminogen activator inhibitor-1 (PAI-1) and the matrix proteins biglycan and collagens type I and IV by Northern and the protein expression of PAI-1 and fibronectin by enzyme-linked immunosorbent assay. RESULTS:While L-NAME strikingly reduced NO biosynthesis and worsened the glomerular filtration rate and CsA-induced fibrosis, L-Arg had the opposite beneficial effect. In addition, the CsA-induced up-regulated expression of TGF-beta1, PAI-1, and the matrix proteins biglycan, fibronectin, and collagen I was significantly increased with L-NAME and strikingly improved with L-Arg. Collagen IV expression was not affected. Also, NO modulation did not affect VH-treated rats. CONCLUSIONS:Chronic CsA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement, suggesting that NO maintains a protective function. NO modulation was associated with a change in TGF-beta1 expression, which, in turn, was associated with alterations in matrix deposition and matrix degradation through its effect on PAI-1.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Shihab FS,Yi H,Bennett WM,Andoh TFdoi
10.1046/j.1523-1755.2000.00273.xsubject
Has Abstractpub_date
2000-09-01 00:00:00pages
1174-85issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47207-2journal_volume
58pub_type
杂志文章abstract::A major problem in cyclosporine A (CsA) therapy is its nephrotoxicity, characterized by a marked fall in glomerular filtration rate (GFR). Since the glomerular ultrafiltration area is an important determinant of GFR and has been proposed to be regulated by mesangial (MS) cell contraction, we examined the effect of CsA...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.149
更新日期:1988-07-01 00:00:00
abstract::Cytomegalovirus (CMV) seropositivity is associated with increased risk for atherosclerotic disease in patients with end-stage renal disease. This association is due to a unique peripheral blood CD4(+) T cell population which lack CD28 (CD4(+)CD28(-) T cells). Here we found that this patient population has a significan...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.301
更新日期:2008-09-01 00:00:00
abstract::To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.201
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:The peritoneum is progressively denuded of its mesothelial cell monolayer in patients on continuous ambulatory peritoneal dialysis (CAPD). These alterations of the mesothelium cause membrane dysfunction and progressive peritoneal fibrosis. Integrins regulate cell motility and play an important role in wound ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00772.x
更新日期:2003-02-01 00:00:00
abstract::Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Reg...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2011.232
更新日期:2011-11-01 00:00:00
abstract::One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 micrograms vaccine...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.18
更新日期:1984-01-01 00:00:00
abstract::In contrast to other nonsteroidal anti-inflammatory drugs (NSAIDs), sulindac has been reported to inhibit systemic prostaglandins (PGs) while not affecting renal PGs. We studied 11 normal volunteers who received placebo, ibuprofen, naproxen, or sulindac in a randomized, double-blind fashion. After control periods asse...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1985.11
更新日期:1985-01-01 00:00:00
abstract::Genetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polym...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.251
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:It has been shown that non-congenic mice strains with lower levels of renal meprin develop less renal injury following renal ischemia and reperfusion. We have demonstrated that following ischemia-reperfusion renal injury, there is a rapid shift of meprin localization and intensity from the brush border to th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00209.x
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00957.x
更新日期:2001-10-01 00:00:00
abstract::Circulating donor-reactive effector memory T cells have been associated with allograft injury in humans. The next step to translate this observation into clinical practice is the design of clinical trials aimed at individualization of T cell-targeted therapy. The administration of immunosuppressive therapy based on th...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.295
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00245.x
更新日期:2005-04-01 00:00:00
abstract::Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathologic...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2012.307
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Normal human podocytes are terminally differentiated and quiescent cells. It is not known why podocytes fail to proliferate in response to most forms of injury. Proliferation is regulated by cell cycle proteins and their inhibitors. The Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21, p27, p5...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00213.x
更新日期:2000-08-01 00:00:00
abstract::Nephropathia epidemica (NE) caused by Puumala hantavirus is one type of hemorrhagic fever with renal syndrome (HFRS). There is considerable variability in the clinical severity of NE. Many infections are subclinical but the disease can even be fatal. We questioned whether the wide spectrum in the outcome of NE is depe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.29
更新日期:1996-01-01 00:00:00
abstract::The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.158
更新日期:1980-10-01 00:00:00
abstract::The Executive Summary of the KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients is presented in this issue of Kidney International. This guideline will require careful attention for implementation in the context of available resources within each country, especially those with underdevelope...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.468
更新日期:2010-02-01 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 risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermi...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5002059
更新日期:2007-03-01 00:00:00
abstract::Intravascular hemolysis is relatively rare but can lead to acute kidney injury (AKI), from increased destruction of erythrocytes and release of free hemoglobin. Since hemolysis and hemoglobinuria are known causes of acute kidney injury we sought to define clinicopathologic findings and outcomes of patients with hemoly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.08.026
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Patients with thin basement membrane disease (TBMD) are often from families where hematuria segregates with the COL4A3 and COL4A4 genes. These genes also are affected in autosomal recessive Alport syndrome. The aim of this study was to demonstrate COL4A4 mutations in TBMD. METHODS:Forty-eight unrelated indi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00780.x
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002682.x
更新日期:2001-02-01 00:00:00
abstract::We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuE...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2011.349
更新日期:2012-02-01 00:00:00
abstract::This study examined the expression of EPO, VEGF and VEGF receptor gene under conditions of reduced oxygen supply in primary cultures of rat hepatocytes, and compared it with the expression of these genes in hypoxic rat livers in vivo. To this end we exposed male Sprague-Dawley rats to hypoxia (10% and 8% O2), carbon m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.60
更新日期:1997-02-01 00:00:00
abstract::In the course of studying the genetics of chlorambucil mutagenesis, we have uncovered a new model for autosomal polycystic kidney disease (PKD). In the homozygous condition, the gene, jcpk, causes a very severe disease characterized by cysts in all segments of the nephron. Death usually occurs before 10 days of age. E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.69
更新日期:1995-02-01 00:00:00
abstract::The essential role of the glycoprotein hormone erythropoietin (Epo) in the control of red blood cell production is well established. Synthesis of Epo is induced in response to low oxygen (hypoxia). In response to stimulation, increases in serum Epo levels are paralleled by changes in the abundance of Epo mRNA. These c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.70
更新日期:1997-02-01 00:00:00
abstract::Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.472
更新日期:2012-06-01 00:00:00
abstract::Osteopontin is an arginine-glycine-aspartate (RGD) containing secreted phosphoprotein recently shown to stimulate a local macrophage influx when injected subcutaneously in mice. We examined the effect of angiotensin II infusion on renal injury and osteopontin expression in the rat kidney by in situ hybridization and i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.67
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND:We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. METHODS:Between April 1999 and June 2002, 30 critically ill sub...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00342.x
更新日期:2005-06-01 00:00:00
abstract::In April 2006, Japan's health insurance system instituted a bundling policy that included recombinant human erythropoietin (rHuEPO) in outpatient hemodialysis therapy. To evaluate outcomes of this, we analyzed a prospective cohort of hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study, in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.382
更新日期:2011-02-01 00:00:00