Abstract:
:We have shown that cisplatin inhibits fatty acid oxidation, and that fibrate treatment ameliorates renal function by preventing the inhibition of fatty acid oxidation and proximal tubule cell death. Urine samples of mice treated with single injection of cisplatin (20 mg/kg body weight) were collected for 3 days and analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy. In a separate group, urine samples of mice treated with peroxisome proliferator-activated receptor-alpha (PPARalpha) ligand WY were also analyzed by NMR after 2 days of cisplatin exposure. Biochemical analysis of endogenous metabolites was performed in serum, urine, and kidney tissue. Electron microscopic studies were carried out to examine the effects of PPARalpha ligand and cisplatin. Principal component analysis demonstrated the presence of glucose, amino acids, and trichloacetic acid cycle metabolites in the urine after 48 h of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also demonstrated the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, in spite of increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of PPARalpha ligand. Electron microscopic analysis confirmed the protective effect of the fibrate on preventing cisplatin-mediated necrosis of the S3 segment of the proximal tubule. Our study shows that cisplatin-induces a unique NMR metabolic profile in urine of mice that developed acute renal failure, and confirms the protective effect of a fibrate class of PPARalpha ligands. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Portilla D,Li S,Nagothu KK,Megyesi J,Kaissling B,Schnackenberg L,Safirstein RL,Beger RDdoi
10.1038/sj.ki.5000433subject
Has Abstractpub_date
2006-06-01 00:00:00pages
2194-204issue
12eissn
0085-2538issn
1523-1755pii
S0085-2538(15)51443-9journal_volume
69pub_type
杂志文章abstract::The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.385
更新日期:1997-09-01 00:00:00
abstract::A new study by Xu et al. presents compelling evidence for an important role of the glomerular endothelium in acute kidney injury. They show that lipopolysaccharide reduces the endothelial surface layer, resulting in mild albuminuria, reduced glomerular filtration rate, and fewer endothelial fenestrae. Tumor necrosis f...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.317
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00420.x
更新日期:1999-05-01 00:00:00
abstract::Tubular atrophy and interstitial fibrosis, important in progression of renal diseases, including diabetic (D) and cyclosporine-induced (CSA) nephropathy, have been considered irreversible. Normoglycemia for 10 years following pancreas transplantation alone (PTA) reversed D glomerulopathy lesions. This study quantified...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000153
更新日期:2006-03-01 00:00:00
abstract::Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mut...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.258
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND:Bioimpedance, a noninvasive technique to analyze body composition, has attracted interest in determining body hydration in hemodialysis patients. However, the so-called whole-body (wrist-to-ankle) bioimpedance analysis (WBIA) is sensitive to changes in regional fluid distribution and tends to underestimate f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00588.x
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintag...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00945.x
更新日期:2000-03-01 00:00:00
abstract::We studied renal autoregulation in pancreatectomized Munich-Wistar diabetic rats and in their sham-operated controls. In a second experiment we studied renal autoregulation in untreated and insulin treated streptozotocin diabetic Munich-Wistar rats and their nondiabetic controls. In the first experiment the diabetic r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.65
更新日期:1990-03-01 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::Heterozygous mutations of the tissue-specific transcription factor hepatocyte nuclear factor (HNF)1beta, cause maturity onset diabetes of the young (MODY5) and kidney anomalies including agenesis, hypoplasia, dysplasia and cysts. Because of these renal anomalies, HNF1beta is classified as a CAKUT (congenital anomalies...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.149
更新日期:2008-07-01 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::We previously demonstrated that urinary endothelin excretion is increased in rats with extensive renal mass reduction, a model of progressive renal disease. Here we explored whether the increased urinary endothelin in this model were due to induction of renal pre-pro-endothelin-1 gene and whether changes in endothelin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.53
更新日期:1993-02-01 00:00:00
abstract::Since 1992 and the discovery of an MIP (major intrinsic protein of lens fiber cell) homologue protein that selectively permeates water, aquaporin (AQP), there has been an explosion of research in this field. Early research speculated that aquaporins played indispensible physiological roles in bacteria and plants, as w...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.1998.00123.x
更新日期:1998-10-01 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::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.216
更新日期:1986-10-01 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 pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.71
更新日期:1984-04-01 00:00:00
abstract::Tenascin-C is an extracellular matrix glycoprotein that plays a critical role in kidney fibrosis by orchestrating a fibrogenic niche. Here, we demonstrate that tenascin-C is a biomarker and a mediator of kidney fibrogenesis by impairing tubular integrity. Tenascin-C was found to be increased in kidney biopsies from pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.026
更新日期:2020-05-01 00:00:00
abstract::Mice chronically infected with the virus of lymphocytic choriomeningitis (LCM) develop immune complex glomerulonephritis. Others have shown that adoptive immunization of these mice by the i.p. injection of syngeneic immune spleen cells terminates the chronic viral carrier state. The present studies were designed to de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.49
更新日期:1977-05-01 00:00:00
abstract::Renal involvement in von Hippel-Lindau (VHL) disease has emerged as the most prevalent cause of death in this hereditary disorder. In a group of 43 VHL patients (23 unrelated families) with renal lesions we examined whether severity of renal disease is affected by parental inheritance and VHL subtype (1, without pheoc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.395
更新日期:1996-09-01 00:00:00
abstract:BACKGROUND:Renal inflammation is regulated by a network of local and systemic mediators. Of them, transforming growth factor-beta1 (TGF-beta 1) and glucocorticoids play an important role in deactivating monocytes/macrophages. We examined the hypothesis that TGF-beta 1 effects may be partially achieved through modulatio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.63.6s.3.x
更新日期:2003-06-01 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::Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.024
更新日期:2018-08-01 00:00:00
abstract::We investigated the effects of epidermal growth factor (EGF) and arginine vasopressin (AVP) on Raf-1-MAP kinase cascade, including Raf-1-kinase (Raf-1-K), MAP kinase kinase (MAPKK), MAP kinase (MAPK) and S6 kinase (S6K) in Madin-Darby canine kidney (MDCK) cells. In a dose-dependent manner (10(-10) M to 10(-6) M), EGF ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.346
更新日期:1995-09-01 00:00:00
abstract::Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteod...
journal_title:Kidney international
pub_type: 共识发展会议,杂志文章
doi:10.1038/sj.ki.5000414
更新日期:2006-06-01 00:00:00
abstract::Intrarenal artery infusions of hypertonic saline can activate tubuloglomerular feedback (TGF), decreasing renal blood flow (RBF) and glomerular filtration rate (GFR). The response to infusion of hypertonic saline is enhanced by salt depletion and attenuated by salt loading, but has not previously been investigated in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.236
更新日期:1987-10-01 00:00:00
abstract::Mutations in the MYH9 gene, coding for the non-muscle myosin heavy chain IIA (NMHC-IIA), are responsible for syndromes characterized by macrothrombocytopenia associated with deafness, cataracts, and severe glomerular disease. Electron microscopy of renal biopsies from these patients found glomerular abnormalities char...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.256
更新日期:2011-11-01 00:00:00
abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00
abstract::About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium ox...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.104
更新日期:2013-06-01 00:00:00
abstract::Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders that can produce an undefined glomerulopathy. To better characterize the glomerular disease associated with myeloproliferative neoplasms, we evaluated features of 11 patients with myeloproliferative neoplasm-related glomerulopathy that included ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.147
更新日期:2011-10-01 00:00:00