Abstract:
:Excess fatty acids accompanied by triglyceride accumulation in parenchymal cells of multiple tissues including skeletal and cardiac myocytes, hepatocytes, and pancreatic beta cells results in chronic cellular dysfunction and injury. The process, now termed lipotoxicity, can account for many manifestations of the 'metabolic syndrome'. Most data suggest that the triglycerides serve primarily a storage function with toxicity deriving mainly from long-chain nonesterified fatty acids (NEFA) and their products such as ceramides and diacylglycerols. In the kidney, filtered NEFA carried on albumin can aggravate the chronic tubule damage and inflammatory phenotype that develop during proteinuric states and lipid loading of both glomerular and tubular cells is a common response to renal injury that contributes to progression of nephropathy. NEFA-induced mitochondrial dysfunction is the primary mechanism for energetic failure of proximal tubules during hypoxia/reoxygenation and persistent increases of tubule cell NEFA and triglycerides occur during acute renal failure in vivo in association with downregulation of mitochondrial and peroxisomal enzymes of beta oxidation. In acute renal failure models, peroxisome proliferator-activated receptor alpha ligand treatment can ameliorate the NEFA and triglyceride accumulation and limits tissue injury likely via both direct tubule actions and anti-inflammatory effects. Both acute and chronic kidney disease are associated with systemic manifestations of the metabolic syndrome.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Weinberg JMdoi
10.1038/sj.ki.5001834subject
Has Abstractpub_date
2006-11-01 00:00:00pages
1560-6issue
9eissn
0085-2538issn
1523-1755pii
S0085-2538(15)52193-5journal_volume
70pub_type
杂志文章,评审abstract::Crim1 is a cell-surface, transmembrane protein that binds to a variety of cystine knot-containing growth factors, including vascular endothelial growth factor A. In the developing renal glomerulus, Crim1 acts to tether vascular endothelial growth factor A to the podocyte cell surface, thus regulating its release to gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.345
更新日期:2009-12-01 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:BACKGROUND:A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Co...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.2003.00720.x
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Cellular and molecular mechanisms responsible for cisplatin-induced nephrotoxicity to renal tubular epithelial cells are not well understood. Although caspases play a critical role in the execution of the cell death pathway, their specific role in toxic injury to renal tubular epithelial cells has not been e...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00026.x
更新日期:2001-11-01 00:00:00
abstract::In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 yea...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2014.114
更新日期:2014-10-01 00:00:00
abstract::One reason for the inadequacy of current renoprotective therapy and the persistent poor renal prognosis in diabetic nephropathy is the large interindividual variation in response to treatment. Genetic as well as non-genetic factors are known to influence treatment efficacy. This Commentary summarizes the impact of the...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000283
更新日期:2006-04-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.217
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Hemodialysis access thrombosis is a significant cause of morbidity for hemodialysis patients and results from decreased access flow caused by venous outflow tract stenosis. Ultrasound dilution (UD) is a practical, noninvasive, and reliable indicator of access flow and is effective in predicting venous stenos...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2001.00753.x
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:Gene expression analysis is an invaluable tool in the study of diabetic glomerulosclerosis. The necessary denominator for the quantitative expression of a specific gene is the expression level of a second gene that is presumed to remain unchanged. Thus, it is critical that the stability of this housekeeping ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.66016.x
更新日期:2004-12-01 00:00:00
abstract::Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.221
更新日期:1990-09-01 00:00:00
abstract::Chemotherapy-induced nephrotoxicity limits the success of cancer therapy. Landau et al. now describe a mechanism by which a first dose of cisplatin renders the kidney sensitive to necroptosis mediated by a second dose. Unresolved injury and sustained necrosis, therefore, may represent a pathophysiological means of tra...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.12.004
更新日期:2019-04-01 00:00:00
abstract::The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.298
更新日期:1992-08-01 00:00:00
abstract::Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2019.02.009
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients. METHODS:A total of 275 (122 men and 153 women; aged 60.6 +/- 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00235.x
更新日期:2005-04-01 00:00:00
abstract::The development of effective therapies for acute kidney injury (AKI) has been hindered by delayed diagnosis in the clinical setting, varying definitions of AKI, and limited prognostic information. In a study by Portilla et al., elevations in liver fatty acid-binding protein (L-FABP) were found to predict AKI in childr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002739
更新日期:2008-02-01 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::The impact of pediatric chronic kidney disease (CKD) on acquisition of volumetric bone mineral density (BMD) and cortical dimensions is lacking. To address this issue, we obtained tibia quantitative computed tomography scans from 103 patients aged 5-21 years with CKD (26 on dialysis) at baseline and 12 months later. G...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.347
更新日期:2013-03-01 00:00:00
abstract::Nephronophthisis is an autosomal recessive kidney disease with high genetic heterogeneity. Understanding the functions of the individual genes contributing to this disease is critical for delineating the pathomechanisms of this disorder. Here, we investigated kidney function of a novel gene associated with nephronopht...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2019.04.014
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS:Rat renal tubular epithelial cells (NRK-52E) ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590041290.x
更新日期:2001-04-01 00:00:00
abstract:INTRODUCTION:Thiazide diuretics have the unique characteristic of increasing renal Na+ excretion, while decreasing Ca2+ excretion. However, the molecular mechanism responsible for this thiazide-induced hypocalciuria remains unclear. The present study investigates the effect of thiazides on the expression of the protein...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00128.x
更新日期:2003-08-01 00:00:00
abstract::We have studied acid-base balance in 32 patients attending the renal clinic of Mount Sinai Hospital. The parameters of acid-base balance measured included acid production measured as urinary sulfate and organic anions, net acid excretion measured as urinary ammonia plus titratable acid minus bicarbonate, and net GI ab...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.79
更新日期:1995-02-01 00:00:00
abstract::Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.359
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND:Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00271.x
更新日期:1999-02-01 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::Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been report...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000300
更新日期:2006-05-01 00:00:00
abstract::We reviewed the diagnostic features and clinical course of 140 patients with idiopathic membranous nephropathy who had their index renal biopsies performed at the Mayo Clinic between 1972 and 1984. There were 93 males and 47 females (average age, 50.8 +/- 17 years); 116 patients (83%) had the nephrotic syndrome and 42...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.56
更新日期:1988-03-01 00:00:00
abstract::Residual renal function is a major survival determinant for peritoneal dialysis patients. Hypovolemia can cause acute kidney injury and loss of residual renal function, and it has been suggested that patients receiving peritoneal dialysis should preferably be maintained hypervolemic to preserve residual renal function...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.273
更新日期:2014-01-01 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::To investigate the cause and the mechanisms responsible of the compulsive thirst and excessive fluid intake observed in many patients on chronic dialysis treatment, we measured plasma antidiuretic hormone (ADH), angiotensin II (Ang II) and some hemodynamic parameters in seven polydipsic and in six normodipsic patients...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.219
更新日期:1993-07-01 00:00:00
abstract::Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.166
更新日期:1979-11-01 00:00:00