Abstract:
:Because the size of renal cysts in the native kidneys of patients with ADPKD who have been transplanted was found to be reduced when rapamycin was the immunosuppressant, we tested the involvement of the mTOR pathway in cyst enlargement. Here, male pcy mice, with mutation in one of the nephronophthisis genes, were treated with rapamycin at an early (6 to 12 weeks of age) or a later (20 to 30 weeks of age) disease stage by means of slow-release pellets containing placebo or rapamycin. Effectiveness of the rapamycin dose and delivery was shown by the inhibition of insulin-stimulated phosphorylation of p70S6K, a marker of mTOR activity, in skeletal muscle. Early treatment did not affect initial cyst development but when started late, there was a significant reduction in the rate of cyst enlargement, kidney fibrosis, and the progressive loss of renal function as measured by blood urea nitrogen. Kidneys of the mice treated through 30 weeks of age tended to be smaller and have less fibrosis compared with those of untreated or placebo-treated pcy/pcy mice at 20 weeks when treatment was initiated. Our study shows that rapamycin can prevent the late- but not the early-stage progression of renal pathology and deterioration of renal functional in this model of nephronophthisis, presumably by inhibiting mTOR activity.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Gattone VH 2nd,Sinders RM,Hornberger TA,Robling AGdoi
10.1038/ki.2009.147subject
Has Abstractpub_date
2009-07-01 00:00:00pages
178-82issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)53941-0journal_volume
76pub_type
杂志文章abstract::Anecdotal reports of complement component deficiencies in patients with immune complex disease led to a systematic study of the levels of seven complement components in serum specimens from 178 patients with glomerulonephritis and 163 normal subjects. Deficiencies were found with significantly higher frequency (22.7%)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.211
更新日期:1983-11-01 00:00:00
abstract::Previously, uremic toxins were sometimes regarded as a large, mysterious, but also anonymous group of factors potentially contributing to morbidity and mortality in end-stage renal disease. By identifying the protein-bound solute p-cresol as a risk factor for mortality in dialysis patients, Bammens and colleagues for ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000236
更新日期:2006-03-01 00:00:00
abstract::Transport and metabolism of adenosine were studied in the S1, S2, and S3 segments of the rabbit proximal renal tubule. Isolated segments were perfused in vitro with uniformly labelled 14C-adenosine to measure the lumen-to-bath flux of adenosine. This flux rate was measured by the disappearance of 14C from the luminal ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.174
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND:Nuclear factor-kappaB (NF-kappaB) and activated protein-1 (AP-1) are transcription factors that regulate many genes involved in the progression of renal disease. Recent data have shown that NF-kappaB is activated in tubules and glomeruli in various experimental models of renal injury. In vitro studies also s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00941.x
更新日期:2001-10-01 00:00:00
abstract::We examined the effect of daily cyclosporin A administration on the development and extent of tubulointerstitial nephritis produced in rats immunized with tubular basement membranes in adjuvant. Six mg/kg/day of cyclosporin A, given from the time of immunization, completely blocked the development of interstitial lesi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.119
更新日期:1988-06-01 00:00:00
abstract::Recent evidence suggesting a strong interplay between components of the renin-angiotensin system and key mediators of fibrosis led us to hypothesize that renin, independent of its enzymatic action to enhance angiotensin (Ang) II synthesis, directly increases production of the fibrogenic cytokine transforming growth fa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000011
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Nitric oxide inactivation by superoxide impairs endothelium-dependent vasodilation and plays a role in various forms of hypertension. Almost no data exist regarding hypertension secondary to chronic renal failure. Previous studies have shown that endothelium-related relaxations, secondary to decreased nitric...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00166.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:The relationship between low hematocrit and contrast-induced nephropathy has not been investigated. METHODS:Of 6,773 consecutive patients treated with percutaneous coronary intervention, contrast-induced nephropathy (an increase of >/=25% or >/=0.5 mg/dL in preprocedure serum creatinine, at 48 hours postpro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67131.x
更新日期:2005-02-01 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::Administration of antibody, directed against glomerular basement membrane (GBM) heparan sulfate-proteoglycan, into a presensitized rat results in the induction of membranous nephropathy with subepithelial immune-complex deposits. In this investigation, we examined the mechanisms responsible for the formation of subepi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.166
更新日期:1988-08-01 00:00:00
abstract:BACKGROUND:In addition to nitric oxide (NO) and prostacyclin (PGI2), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00910.x
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:The inhibitor of apoptosis (IAP) family of proteins regulates programmed cell death triggered by various stimuli. The purpose of this investigation was to examine the expression, regulation, and function of IAP genes in cultured rat mesangial cells. METHODS:Basal and inducible expression of c-IAP1, c-IAP2, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002579.x
更新日期:2001-08-01 00:00:00
abstract::Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosupp...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002306
更新日期:2007-06-01 00:00:00
abstract::Pain was surveyed via structured interview and the McGill Pain Questionnaire in 53 dialysis and 27 transplant patients. Increased patient control over the dialysis procedure was not associated with a reduction in pain though perceived control may have been. Compliance with the dialysis regimen did not predict pain and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.108
更新日期:1982-06-01 00:00:00
abstract::The purpose of this investigation is to analyze changes in plasma 1,25-(OH)2D and 24,25-(OH)2D after successful renal transplantation in 20 children and young adults. Studies were performed on 8 subjects between the 1st and 10th month and on 12 others between the 20th and 30th to 36th month. Samples were assayed for p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.153
更新日期:1981-09-01 00:00:00
abstract::The vasopressin inhibitor tolvaptan is clinically effective in slowing growth of renal cysts and reduction in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD), but these effects are mitigated by the associated polyuria. Changes of total kidney volume, eGFR, and sympto...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.143
更新日期:2015-07-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis w...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1991.268
更新日期:1991-10-01 00:00:00
abstract::Kinetic parameters were studied to determine the effectiveness of hemoperfusion in removing ethychlorvynol from the plasma and red blood cells (RBC) of intoxicated dogs. Perfusion columns contained polystyrene/divinyl benzene resin (XAD-4 Amberlite. Column clearances of ethchlorvynol averaged 96.5 +/- 0.4% of the plas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.36
更新日期:1980-03-01 00:00:00
abstract::Macrophages are inflammatory cells with important roles in the propagation of renal injury. More recently they have also been shown to be important in the resolution of inflammation. Wang et al. show that macrophages can be modulated ex vivo by cytokine stimulation, localize to renal tissue, and slow progression of ex...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002332
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Intrauterine growth retardation (IUGR) is associated with higher morbidity and mortality not only in perinatal life but also in later life. The purpose of our study was to determine whether IUGR has any effect on the course of minimal change nephrotic syndrome (MCNS) in children. METHODS:Forty children who ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00121.x
更新日期:1998-10-01 00:00:00
abstract::Nephrin is a slit diaphragm protein critical for structural and functional integrity of visceral glomerular epithelial cells (podocytes) and is known to be tyrosine phosphorylated by Src family kinases. We studied the role of phosphoinositide 3-kinase (PI3K), activated via the phosphorylation of nephrin, in actin cyto...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002691
更新日期:2008-03-01 00:00:00
abstract::The primary hyperoxalurias are diseases of overproduction of oxalate. The immediate precursor of oxalate is glyoxylate. Metabolism of hydroxyproline, derived from collagen turnover or the diet, appears to be a major source of glyoxylate, and a potential target for a therapeutic strategy of substrate depletion. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001987
更新日期:2006-12-01 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::Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001853
更新日期:2006-11-01 00:00:00
abstract::Adenosine is known to be a potent inhibitor of renin release from the kidneys. The aim of this study was to investigate the transmembrane signalling avenue that the second messenger of adenosine causes inhibition of renal renin release. Using short term cultures of juxtaglomerular cells isolated from rat kidneys, we f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.70
更新日期:1988-04-01 00:00:00
abstract::In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.235
更新日期:1988-11-01 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:BACKGROUND:Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS:Physiologic techniques were used to estimate glomerular filtrati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00097.x
更新日期:1998-10-01 00:00:00
abstract::Zhang and co-workers report on the renoprotective role of the vitamin D receptor (VDR) in diabetic nephropathy using the method of streptozotocin-induced hyperglycemia in wild-type and VDR(-/-) mice. Also, experiments with cultured mesangial cells and podocytes confirm the effect of the active vitamin D metabolite 1,2...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002693
更新日期:2008-01-01 00:00:00
abstract::Renal sodium reabsorption is a key determinant of final urine concentration. Our aim was to determine whether differences existed between aged and young rats in their response to water restriction with regard to the regulation of abundance of any of the major distal renal sodium transporter proteins. Male Fisher 344 x...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000076
更新日期:2006-01-01 00:00:00