Abstract:
:The selective vasopressin V2-receptor antagonist tolvaptan is eliminated almost exclusively by non-renal mechanisms. As renal impairment can influence the pharmacokinetics of drugs even when eliminated by non-renal mechanisms, we evaluated the effect of renal insufficiency on the pharmacokinetics/pharmacodynamics of tolvaptan. Thirty-seven patients were grouped by a 24-h creatinine clearance (CrCL) and evaluated for 48 h after a single 60 mg oral dose in the fasting state. Mean tolvaptan exposure was 90% higher in the under 30-ml/min group compared with the over 60-ml/min group with individual values significantly but negatively correlated with increasing baseline CrCL. There was a greater and more rapid increase in urine output and free water clearance in the over 60-ml/min compared with the renal impaired groups, but they returned to baseline more quickly. Serum sodium increased more rapidly in the over 60 as opposed to the under 30-ml/min group, but overall maximum increases were similar across groups. Small decreases in mean CrCL and small increases in mean serum creatinine/potassium were independent of baseline CrCL. The percent fractional free water clearance with respect to CrCL was significantly but negatively correlated with increasing baseline CrCL. No unexpected adverse events were reported. Thus, renal impairment attenuated the increase in 24-h urine volume and free water clearance caused by tolvaptan, consistent with decreased nephron function in renal impairment. The delay in serum sodium increase was consistent with the longer duration needed to excrete sufficient water to cause the increase.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Shoaf SE,Bricmont P,Mallikaarjun Sdoi
10.1038/ki.2013.350subject
Has Abstractpub_date
2014-04-01 00:00:00pages
953-61issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)56272-8journal_volume
85pub_type
临床试验,杂志文章abstract:BACKGROUND:The pathogenesis of progressive nephropathies involves hemodynamic and inflammatory factors. In the 5/6 nephrectomy model, a selective increase of cyclooxygenase-2 (COX-2) expression was shown, whereas treatment with a nonsteroidal anti-inflammatory or a specific COX-2 inhibitor was renoprotective. We invest...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00319.x
更新日期:2003-12-01 00:00:00
abstract::11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) transforms endogenous glucocorticoids to their respective "biologically inert" 11-dehydro derivatives. A decrease in enzyme activity allows glucocorticoids to induce mineralocorticoid-like renal sodium retention. Since positive sodium balance is required for optimum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.91
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00370.x
更新日期:2004-01-01 00:00:00
abstract::Hypertriglyceridemia in nephrotic (NS) and Nagase analbuminemic rats (Analb) results from reduced triglyceride clearance. NS and Analb have reduced or absent albumin, reduced plasma oncotic pressure (pi), but Analb lack proteinuria. The heparin releasable lipoprotein lipase (LpL) pool in both models is greatly reduced...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000318
更新日期:2006-08-01 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::Donor pretreatment of 100 mg/kg each of cyclophosphamide (CY) and methylprednisolone (P) infused 5 hours before nephrectomy invariably prolongs the survival of DLA mismatched, MLC incompatible nonlittermate Beagle renal allografts as well as the survival of mongrel renal allografts. The effect of donor pretreatment ap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.25
更新日期:1982-02-01 00:00:00
abstract::Aboriginal dialysis patients have reduced access to kidney transplantation. The reasons for this disparity are unknown. Tonelli et al. show that in Canada, residence location does not significantly impact on an Aboriginal dialysis patient's likelihood of receiving kidney transplantation. This Commentary explores the i...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001762
更新日期:2006-09-01 00:00:00
abstract::Cystinosis as a clinical entity is a progressive dysfunction of multiple organs caused by the accumulation of cystine in the tissues, leading, for example, to end-stage renal failure, diabetes, hypothyroidism, myopathy, and central nervous system deterioration. Brodin-Sartorius and colleagues present a long-term study...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.301
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Monocyte chemoattractant protein-1 (MCP-1) promotes renal inflammation, thereby contributing to acute and chronic nephropathies. Its production is stimulated by oxidative stress. Thus, this study tested whether pro-oxidant iron/carbohydrate complexes, used to treat iron deficiency, induce MCP-1 in renal/ex...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00565.x
更新日期:2005-10-01 00:00:00
abstract::Previous work has documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheter...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.223
更新日期:1992-06-01 00:00:00
abstract::Substrate oxidation was assessed by measuring 14CO2 production from 14C-labeled substrates in proximal convoluted tubules (PCT), medullary (MTAL), and cortical (CTAL) thick ascending limb of Henle, nephron segments rich in mitochondria and characterized by active solute transport. PCT, MTAL, and CTAL were dissected fr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.100
更新日期:1981-07-01 00:00:00
abstract:BACKGROUND:The next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00295.x
更新日期:2000-09-01 00:00:00
abstract::During the heterologous phase of experimental anti-glomerular basement membrane (anti-GBM) nephritis, leukocyte influx peaks within hours, whereas albuminuria occurs within 1 day. In the subsequent autologous phase, endogenous anti-GBM IgG develops and albuminuria persists. Heparan sulfate (HS) proteoglycans like synd...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002514
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is mark...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00580.x
更新日期:2004-05-01 00:00:00
abstract::Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell typ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.562
更新日期:2010-04-01 00:00:00
abstract:BACKGROUND:Nephrologists report that patients' choice should play an important role in the selection of renal replacement therapy (RRT) for end-stage renal disease (ESRD). In the United States, kidney transplant rates remain low and <10% of patients utilize home dialysis therapies. This study examined the effect of pre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00453.x
更新日期:2005-07-01 00:00:00
abstract::Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular h...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2015.306
更新日期:2016-03-01 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
abstract::Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-ac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.75
更新日期:1991-04-01 00:00:00
abstract::Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000273
更新日期:2006-04-01 00:00:00
abstract::As an alternative to classical immunosuppressants in experimental lupus nephritis, we looked at bindarit, 2-methyl-2-[[1-phenylmethyl)-1H-indazol-3-y1]methoxy]propanoic acid, a novel molecule devoid of immunosuppressive effects, which selectively reduces chronic inflammation in rat adjuvant arthritis. Two groups of NZ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00804.x
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND:Although renal protective effect of interrupting the inflammatory process is well established, it is still controversial if it also prevents the glomerular hemodynamic disturbances that initiate renal injury. We investigated the effects of suppressing inflammation with mycophenolate mofetil (MMF) on glomerul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00811.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:alpha 2 Macroglobulin (alpha 2M), a protease inhibitor, is often increased in plasma of patients with the nephrotic syndrome. Although it has been speculated that synthesis is increased, no direct measurements have been performed. METHODS:alpha 2M synthesis in both normal subjects (N = 4) and nephrotic pati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00018.x
更新日期:1998-08-01 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:BACKGROUND:We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model. METHODS:Rats were treated for 12 weeks with either lead...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00670.x
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00493.x
更新日期:2005-09-01 00:00:00
abstract::Intravenous conjugated estrogens reduce the prolonged bleeding time in uremic patients and in a rat model of uremia. However, estrogens have major side effects related to their hormonal activity. We investigated whether a beta-resorcylic acid lactone, zeranol (a compound with close spatial similarity to estrogens but ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.172
更新日期:1990-07-01 00:00:00
abstract::Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production a...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002007
更新日期:2006-12-01 00:00:00
abstract::Swelling activated anion channels have recently been recognized to play an important role in not only volume regulatory electrolyte movement, but also in organic osmolyte transport. A swelling-activated, outwardly rectifying anion channel termed VSOAC (volume-sensitive organic osmolyte/anion channel) is a major pathwa...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.250
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on bra...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590041473.x
更新日期:2001-04-01 00:00:00