Abstract:
:Cyclosporine A (CsA) is a potent immunosuppressive drug that inhibits the transcription of several proinflammatory cytokines including interleukin-2. In contrast, CsA stimulates transcription of the pleuripotent cytokine, transforming growth factor-beta (TGF beta). Since the effect of CsA in transplant recipients is unpredictable, we examined whether tissue levels of TGF beta protein in renal allografts correlate with in vivo CsA responsiveness. Intra-allograft TGF beta protein content was assessed in renal biopsies by immunohistochemical means using the mouse anti-TGF beta monoclonal antibody (Mab), 1D11. We studied 68 specimens: 21 with acute CsA toxicity (ACT), 11 with acute tubular necrosis (ATN) and 36 with acute cellular rejection (ACR). Intensity of TGF beta immunostaining was evaluated in a blinded fashion using a scale from 0 to 3+. In biopsies with histological evidence of CsA toxicity, 77% demonstrated intense (2 to 3+) TGF beta immunostaining. TGF beta protein was detected in both proximal and distal tubules but was either absent or present in low levels within glomeruli and interstitium. In contrast, only one of the 11 biopsies with ATN had minimal staining (1+) for TGF beta. The remaining 10 biopsies with ATN were negative for TGF beta immunostaining. In biopsies with ACR, the levels of renal TGF beta were more variable with 36% showing intense (2 to 3+) staining and 64% having minimal or no (0 to 1+) tubular TGF beta. Within the first 18 months post-transplantation, patients with intense TGF beta staining and ACR underwent an average of 4.1 +/- 1.8 allograft biopsies and suffered 33% graft losses. During the same period of time, the patients with ACR and absent or low (0 to 1+) TGF beta levels underwent only 2.1 +/- 1.2 biopsies, maintained better late renal function and suffered 4% graft losses. In conclusion, we demonstrate that TGF beta protein levels in renal allografts correlate with CsA effect and differentiate ACT from ATN. In CsA treated patients who develop ACR, TGF beta levels predict the subsequent clinical course and graft function. Therefore, evaluating tissue levels of TGF beta may offer unique diagnostic and prognostic benefits in the care of patients receiving CsA based immunosuppression.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Pankewycz OG,Miao L,Isaacs R,Guan J,Pruett T,Haussmann G,Sturgill BCdoi
10.1038/ki.1996.479subject
Has Abstractpub_date
1996-11-01 00:00:00pages
1634-40issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)59773-1journal_volume
50pub_type
临床试验,杂志文章abstract::The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.198
更新日期:1990-08-01 00:00:00
abstract::A study of dialysis costs in five major dialysis centers throughout the United States was conducted in 1973. When available, home, home training, limited care, satellite and in-hospital-full-care dialysis were included. The study's objective was to determine the cost per dialysis for each separate dialysis modality. A...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.31
更新日期:1976-03-01 00:00:00
abstract::Mutations in the inverted formin 2 gene (INF2) have recently been identified as the most common cause of autosomal dominant focal and segmental glomerulosclerosis (FSGS). To quantify the contribution of various genes contributing to FSGS, we sequenced INF2 where all mutations have previously been described (exons 2 to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.349
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Strict glycemic control and antihypertensive treatment may decrease but not eliminate the risk of progressive nephropathy in diabetic patients. C-peptide has been shown to exert beneficial effects on complications, including incipient nephropathy, in type 1 diabetes. METHODS:Renal effects of 14 days of intr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00964.x
更新日期:2001-10-01 00:00:00
abstract::The increasing use of mice in renal and cardiovascular studies has necessitated adapting physiological methods used for rats to mice, which are far smaller in size. We have adapted measurements of continuous renal blood flow, pressure natriuresis and diuresis, and laser-Doppler cortical and medullary flow to 40 g mice...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.462
更新日期:1997-11-01 00:00:00
abstract::The International Pediatric Peritonitis Registry (IPPR) was created to assess and evaluate the validity of the pediatric peritonitis treatment guidelines issued by the International Society for Peritoneal Dialysis. The study by Schaefer et al., one of the first to emerge from the IPPR, describes regional variability i...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002529
更新日期:2007-12-01 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
abstract:BACKGROUND:Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of free radicals and has the antioxidant ability to inhibit lipid peroxidation. Its protective effect on brain ischemia has been shown. This study aimed to elucidate its possible therapeutic effects on renal oxidative stress in a rat ische...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00567.x
更新日期:2004-05-01 00:00:00
abstract::IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with l...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.466
更新日期:2011-03-01 00:00:00
abstract::To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.95
更新日期:1990-04-01 00:00:00
abstract::The present study examined the effect of elevated glucose on glomerular cell membrane lipid peroxidation. Glomeruli were isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method and incubated in medium containing different concentrations of glucose at 37 degrees C for one and 48 hours. The lev...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.461
更新日期:1994-12-01 00:00:00
abstract:UNLABELLED:A non-nucleotide-bridged DNA decoy inhibits renal epithelial nitric oxide synthase expression. BACKGROUND:The expression of inducible nitric oxide synthase (iNOS) is subject to strict tissue-specific transcriptional control. In mouse renal epithelium, an interferon-gamma (IFN-gamma)-induced signaling protei...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00809.x
更新日期:2000-01-01 00:00:00
abstract::Sodium depletion has a protective effect on target-organ damage in hypertension independent of blood pressure. Here we tested whether chronic dietary sodium restriction may prevent the development of renal alterations associated with insulin resistance by reducing the inflammatory and oxidant state. Rats were fed norm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.478
更新日期:2013-04-01 00:00:00
abstract::Reliable estimates of the long-term outcomes of acute kidney injury (AKI) are needed to inform clinical practice and guide allocation of health care resources. This systematic review and meta-analysis aimed to quantify the association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD), and d...
journal_title:Kidney international
pub_type: 杂志文章,meta分析
doi:10.1016/j.kint.2018.08.036
更新日期:2019-01-01 00:00:00
abstract::The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient. Hypercalcemia (5.48 +/- 0.03 mEq/liter in high PTH animals, 4...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.68
更新日期:1982-04-01 00:00:00
abstract::Sustained oliguria during fluid resuscitation represents a perplexing problem in patients undergoing therapy for septic acute kidney injury. Here, we tested whether lipopolysaccharide induces filtrate leakage from the proximal tubular lumen into the interstitium, thus disturbing the recovery of urine output during the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.11.024
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND:The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts. METHODS:In this randomized, cross-over, placebo-controlled trial ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00395.x
更新日期:2005-07-01 00:00:00
abstract::We have recently presented evidence that endogenous nitric oxide (NO) and prostaglandins (PGs) modulate angiotensin II (Ang II) action in microperfused afferent arterioles (Af-Arts). Because flow may be a physiological stimulus of endothelial release of NO and PGs, we tested the hypothesis that flow through the lumen ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.55
更新日期:1996-02-01 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::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:It is currently impossible to reliably predict which diabetic patients will develop nephropathy and progress to kidney failure. Microalbuminuria, often regarded as a predictor of overt diabetic renal disease is, in fact, an indicator of established glomerular damage. We have shown that glomerular expression ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00130.x
更新日期:2003-08-01 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:Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the purom...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060003957.x
更新日期:2001-09-01 00:00:00
abstract::The effect of glycine on hypoxia- and ionomycin-induced increases in calpain activity in rat proximal tubules was determined. Calpain activity was determined both in vitro and in the intact cell using the fluorescent substrate N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl coumarin (N-succinyl-Leu-Leu-Val-Tyr-AMC) and We...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.452
更新日期:1997-11-01 00:00:00
abstract::Glomerular podocytes are terminally differentiated cells, and podocyte loss is a common feature of progressive renal pathologies. In this issue, Romoli et al. focus on podocyte progenitors that were proposed to reside in the Bowman's capsule. They demonstrate that suppression of CXCL12/CXCR4 signaling activates pariet...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.09.011
更新日期:2018-12-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:The growth hormone (GH)/insulin-like growth factor (IGF) system is thought to participate in the glomerulosclerosis process. Because IGF-binding proteins (IGFBPs) modulate IGF actions and hence GH secretion, this study assessed whether mice transgenic for human IGFBP-1 have altered susceptibility to glomerul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00090.x
更新日期:2000-06-01 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::Increasing evidence points to the importance of aberrant O-glycosylated immunoglobulin A1 (IgA1) in the pathogenesis of IgA nephropathy (IgAN), a disease widely considered to be a polygenic disorder. We earlier found that haplotypes in two key glycosyltransferase genes, C1GALT1 and ST6GALNAC2, were associated with sus...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.99
更新日期:2009-07-01 00:00:00
abstract::The role of immunoglobulin (Ig) Fc-macrophage cell surface receptor affinity (macrophage Fc-affinity) in determining the mediation systems responsible for immune glomerular injury has been studied. Glomerular injury was initiated in rabbits by the passive administration of immunoglobulin preparations directed against ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.228
更新日期:1989-10-01 00:00:00