Abstract:
BACKGROUND:Diabetic nephropathy is commonly associated with renal salt and water retention and hypertension. The molecular mechanisms involved and how the kidney responds to this volume expansion, in terms of renal transporter regulation, are not understood. METHODS:Targeted proteomics employing semiquantitative immunoblotting were used to investigate regulation of abundance of the primary salt and water transport proteins of the kidney, in 6-month-old lean and obese Zucker rats, a model for Type II diabetes. RESULTS:Obese rats were significantly heavier, had larger kidneys, increased plasma creatinine and glucose levels and elevated blood pressures. Furthermore, they had a marked decrease in abundance of many pre-macula densa renal sodium transporters. Mean band densities (% lean) were: in cortex, sodium phosphate cotransporter (NaPi-2), 68%, and sodium hydrogen exchanger (NHE3), 66%; and in outer medulla, NHE3, 39%, and the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), 37%. Collecting duct proteins also were markedly reduced. In inner medulla, aquaporins-2, -3, and -4 were reduced to, 46, 48, and 46%, respectively, and the apical urea transporter, UTA1 to 52%. In contrast, post-macula densa sodium transporters were less affected. The thiazide-sensitive Na-Cl cotransporter (NCC) was 106% and the alpha- beta- and gamma-subunits of the epithelial sodium channel (ENaC), 54, 121, and 84% of lean, respectively. CONCLUSIONS:In obese rats, selective decreases for pre-macula densa sodium transporters may reflect decreased glomerular filtration rate and glomerulotubular balance. This potentially could reduce blood pressure by decreasing proximal tubule sodium reabsorption.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Bickel CA,Knepper MA,Verbalis JG,Ecelbarger CAdoi
10.1046/j.1523-1755.2002.00353.xsubject
Has Abstractpub_date
2002-06-01 00:00:00pages
2099-110issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48459-5journal_volume
61pub_type
杂志文章abstract::To examine whether hypoxia-inducible factor (HIF)-1α mediates the profibrotic effects of angiotensin II, we treated cultured renal medullary interstitial cells with angiotensin II and found that it increased HIF-1α levels. This was accompanied by a significant upregulation of collagen I/III, the tissue inhibitor of me...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.326
更新日期:2011-02-01 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
abstract::Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) dai...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.93
更新日期:1975-09-01 00:00:00
abstract::Our findings indicate that hypoaldosteronism occurs commonly (23/31 patients) in hyperkalemic patients with chronic renal insufficiency and that the deficiency of aldosterone contributes to the pathogenesis of the hyperkalemia. In most patients (83%), hypoaldosteronism could be accounted for by deficient renal secreti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.11
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:Adrenomedullin (ADM) exerts antiproliferative effects on rat mesangial cells in vitro and, therefore is a possible renoprotective agent. In contrast, nitric oxide (NO) is capable of exerting both cytoprotective and cytotoxic actions. It was the objective of the present study to examine whether NO stimulates ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00330.x
更新日期:2002-05-01 00:00:00
abstract::Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who fil...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.444
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00244.x
更新日期:1999-01-01 00:00:00
abstract::The neonatal proximal tubule has a lower rate of bicarbonate absorption than that of adults. This is due, in part, to a lower rate of apical membrane Na+/H+ antiporter activity. The purpose of these studies was to examine if thyroid hormone could be a factor in the maturational increase in Na+/H+ antiporter activity. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00879.x
更新日期:1998-05-01 00:00:00
abstract::Alterations in red blood cell sodium (Na) transport have been described in chronic renal failure. This study examines the possible impact of uremia on two ouabain-insensitive pathways, the Na/H antiporter and the Cl-/NaCO3- anion exchanger. The Vmax of Na/H antiporter measured as Na influx driven by outward H gradient...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.283
更新日期:1993-09-01 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::The possibility that the rabbit collecting tubule is heterogeneous with respect to electrical and morphologic properties was examined in isolated segments. Collecting tubules from rabbits treated with desoxycorticosterone acetate were dissected from various locations within the cortex and outer medulla, and the transe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.167
更新日期:1978-12-01 00:00:00
abstract::Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.376
更新日期:1992-10-01 00:00:00
abstract::In organ donation, the donor, recipient, and transplant team must all accept potential health risks to the donor and any uncertainties. To gauge these risks, we surveyed general altruism and risk-taking behaviors in 112 potential donors, 111 potential recipients, and 51 transplant professionals. Next, participants ind...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.65
更新日期:2008-05-01 00:00:00
abstract::Unilateral ureteral obstruction in rabbits leads to an influx of macrophages into the kidney, a proliferation of interstitial cells, and an increase in arachidonic acid metabolism. The role of the macrophage in the metabolic changes of hydronephrosis was investigated by using endotoxin and nitrogen mustard. The in viv...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.127
更新日期:1984-07-01 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 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
abstract::The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.63
更新日期:2009-06-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of E...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.435
更新日期:2013-05-01 00:00:00
abstract::Acute kidney injury (AKI) is a major complication of cardiac bypass surgery. We examined whether levels of liver fatty acid-binding protein (L-FABP) can be an early biomarker for ischemic injury by measuring this protein in the urine of 40 pediatric patients prior to and following cardiopulmonary bypass surgery. AKI w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002721
更新日期:2008-02-01 00:00:00
abstract::Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.6
更新日期:1976-01-01 00:00:00
abstract::How the dialysis dose is normalized is just one of several assumptions that clinicians need to take into account when prescribing peritoneal dialysis. El-Kateb et al. confirm that estimating the volume of urea distribution is associated with significant error and show that energy expenditure is not linearly related to...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.09.020
更新日期:2016-12-01 00:00:00
abstract::The present study examined the effect of sodium transport inhibition by amiloride, ouabain, and luminal sodium removal on potassium secretion in isolated cortical collecting tubules from adrenalectomized and DOCA-stimulated rabbits. Collecting tubules from adrenalectomized rabbits had a mean potassium secretion of 3.6...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.96
更新日期:1985-06-01 00:00:00
abstract::The introduction of two-photon microscopy, along with the development of new fluorescent probes and innovative computer software, has advanced the study of intracellular and intercellular processes in the tissues of living organisms. Researchers can now determine the distribution, behavior, and interactions of labeled...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002315
更新日期:2007-08-01 00:00:00
abstract::Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.08.028
更新日期:2017-01-01 00:00:00
abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract::Kidney transplant patients receiving phenytoin or phenobarbital may have decreased graft survival. These drugs have been shown to enhance the metabolism of glucocorticoids. We determined the disposition of total and unbound prednisolone in six stable kidney transplant patients receiving prednisone for immunosuppressio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.17
更新日期:1984-01-01 00:00:00
abstract::When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.332
更新日期:2009-11-01 00:00:00
abstract::Since the kidney medulla was reported to generate platelet activating factor (PAF), we investigated a possible effect of this agent on the reabsorptive function of in vitro microperfused medullary thick ascending limbs from mouse kidney (mTAL). PAF, 10(-7) M in the bath, significantly decreased the net chloride flux (...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.38
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Optimal nutrient intake is important in the maintenance of a positive nitrogen balance in hemodialysis (HD) patients. The objectives of this study were (1) to assess the influence of two levels of protein intakes on nitrogen balance in stable adult HD patients, and (2) to identify a minimum level of protein ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00171.x
更新日期:2000-07-01 00:00:00
abstract::The improvement in the anemia in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) suggests that dialyzable substances present in the sera of uremic patients either inhibit erythropoiesis directly or inactivate erythropoietin (EPO). In the present study predialysis sera f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.88
更新日期:1991-04-01 00:00:00