Abstract:
:The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL plays an important role in the initiation and progression of atherosclerosis. It has also been demonstrated that CsA may facilitate lipid peroxidation in vitro and in vivo. Therefore, we determined several parameters of LDL oxidizability in renal transplant recipients who were switched from CsA to azathioprine (AZA)-based immunosuppressive treatment. The susceptibility of LDL to in vitro oxidation, LDL particle size, plasma titers of IgG and IgM antibodies against oxidized LDL and plasma LDL subclass patterns in 19 renal transplant recipients were determined during CsA treatment and 16 weeks after these patients were converted to AZA treatment. In addition, mean arterial pressure was recorded, and glomerular filtration rate and renal blood flow were estimated from the clearance of radiolabeled thalamate and hippurate. After conversion, the plasma concentrations of total cholesterol, LDL cholesterol and triglyceride decreased, while plasma HDL cholesterol did not change. During CsA therapy plasma LDL was significantly more susceptible to in vitro oxidation than during AZA, as reflected by a longer lag phase during in vitro oxidation (98.9 +/- 24.3 vs. 114.7 +/- 17.3 min, P = 0.031). In addition, the LDL size increased (236.5 +/- 7.3 vs. 240.7 +/- 6.8 nm, P = 0.00001), and the titers of IgM- and IgG-autoantibodies against oxidized LDL decreased significantly after patients were converted from CsA to AZA. The more atherogenic LDL subclass pattern B was present in 13 out of 19 patients during CsA. In five patients, pattern B changed into pattern A after conversion. The subclass B pattern was maintained in eight patients and subclass A pattern in six patients. In all patients the lag time of in vitro LDL oxidation increased, although the biggest changes were found in those patients in whom the LDL subclass changed from pattern B to pattern A. Mean arterial pressure decreased and renal function improved significantly after conversion. No correlation between parameters of lipid peroxidation and changes in blood pressure or renal function upon conversion, underlying renal disease, time since transplantation, or antihypertensive treatment was found. Our study demonstrates that treatment with CsA increases the susceptibility of LDL to in vitro oxidation, and also enhances the oxidation of LDL in vivo. In addition, conversion to AZA results in a more favorable lipid profile, which in combination with a lower arterial pressure and better renal function may decrease the risk for atherosclerosis. These factors may account for the cardiovascular complications during CsA treatment after organ transplantation, and also when CsA is used for other diseases.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
van den Dorpel MA,Ghanem H,Rischen-Vos J,Man in't Veld AJ,Jansen H,Weimar Wdoi
10.1038/ki.1997.221subject
Has Abstractpub_date
1997-05-01 00:00:00pages
1608-12issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)60061-8journal_volume
51pub_type
临床试验,杂志文章,随机对照试验abstract::Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (associated with dietary phosphate restriction in the latter case) on the apical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutamyl-transferase and alkaline-phosphatase...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.485
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND:It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors (controls) on kidney disease...
journal_title:Kidney international
pub_type: 杂志文章,meta分析
doi:10.1111/j.1523-1755.2005.00077.x
更新日期:2005-01-01 00:00:00
abstract::The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.048
更新日期:2016-06-01 00:00:00
abstract::To date direct evidence for the presence of a H-K-ATPase in the medulla comes from proton and potassium transport studies performed on K-restricted animals and K dependent ATP hydrolysis and Rb uptake in both normal and K-depleted animals. The present work examines K-dependent acidification in the medulla of rabbits o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.392
更新日期:1992-11-01 00:00:00
abstract:UNLABELLED:Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. BACKGROUND:To predict the risk of developing chronic renal failure in patients with primary focal glomerulosclerosis (FGS) using predictors available at the time of presentation, a retrospective analysis was perform...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.4491164
更新日期:1999-12-01 00:00:00
abstract::Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.195
更新日期:1980-12-01 00:00:00
abstract::Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-induc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.010
更新日期:2017-08-01 00:00:00
abstract::Progressive glomerulonephritis and attendant end-stage renal disease (ESRD) result from antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The optimum time of kidney transplantation in patients with ESRD due to ANCA-associated vasculitis (AAV) and the risk of renal or nonrenal recurrence of vasculitis a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002244
更新日期:2007-06-01 00:00:00
abstract::The distribution of precursor nitrogen between urea and glutamine was studied in control and acidotic rats. Acidosis, either acutely induced with hydrochloric acid or chronically induced with ammonium chloride, resulted in a rise in ammonia and a fall in urinary urea excretion; the percent of urinary nitrogen excreted...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.182
更新日期:1981-11-01 00:00:00
abstract::To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.289
更新日期:2009-10-01 00:00:00
abstract::Risk factors for disease states are rigorously defined. This analysis considers the definition of a risk factor as applied to the question of whether the serum phosphorus level is a risk factor for cardiovascular disease. Observational studies strongly suggest that phosphorus is associated with cardiovascular risk, an...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.24
更新日期:2011-04-01 00:00:00
abstract::The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.40
更新日期:1990-02-01 00:00:00
abstract::The vascular endothelium normally is maintained in a quiescent state, but under certain conditions it is induced to undergo marked changes in behavior and form new vascular structures. A complex interaction among various growth and differentiation factors and the extracellular milieu regulates this behavior. One serie...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1993.5
更新日期:1993-01-01 00:00:00
abstract::Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.239
更新日期:2015-12-01 00:00:00
abstract::We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuE...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2011.349
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Arteriovenous (AV) fistulas used for hemodialysis access may affect cardiac load by increasing the preload while decreasing the afterload. In dogs, AV fistulas have also been shown to affect coronary perfusion negatively. We investigated the net effect of AV fistulas on cardiac oxygen supply and demand. MET...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00433.x
更新日期:1999-05-01 00:00:00
abstract::Although the goal glomerular filtration rate (GFR) for chronic dialysis initiation is currently above 5 ml/min per 1.73 m(2), there is no convincing evidence that patients will benefit from this approach. With close follow-up of advanced chronic kidney disease patients, aiming to start dialysis at an estimated GFR (eG...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.164
更新日期:2014-10-01 00:00:00
abstract::The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.179
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Fistula failure has been classified as early and late. Early failure refers to those cases in which the arteriovenous (AV) fistula never develops to the point that it can be used or fails within the first 3 months of usage. It has been common practice to abandon these early failures; however, aggressive eval...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00210.x
更新日期:2003-10-01 00:00:00
abstract::We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a signific...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.267
更新日期:1987-11-01 00:00:00
abstract::Bikunin is a chondroitin-sulphate containing serum protein with a Stokes-Einstein radius and a negative net charge close to those of serum albumin. The plasma half life of bikunin is about 10 minutes, and approximately half of its clearance occurs in the kidneys. The quantitative role of glomerular filtration in the r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.147
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:Aldosterone has been suggested to play a role in the initiation and progression of diabetic nephropathy. Currently recommended treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers [renin-angiotensin system (RAS) blockade] does not suppress circulating aldosterone ...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00756.x
更新日期:2005-12-01 00:00:00
abstract::Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.472
更新日期:2012-06-01 00:00:00
abstract::Aminopeptidase A is one of the most potent enzymes within the renin-angiotensin system in terms of angiotensin II degradation. Here, we examined whether there is a kidney phenotype and any compensatory changes in other renin angiotensin system enzymes involved in the metabolism of angiotensin II associated with aminop...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.11.012
更新日期:2020-12-11 00:00:00
abstract::Recently, 4 new risk scores for the prediction of mortality and cardiovascular events were especially tailored for hemodialysis patients; these scores performed much better than previous scores. Tripepi et al. found that these risk scores were even more predictive for all-cause and cardiovascular death than the measur...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.11.022
更新日期:2017-03-01 00:00:00
abstract::Vascular calcification is recognized as a major contributor to cardiovascular disease (CVD) in end stage renal disease (ESRD) patients. Susceptibility to vascular calcification is genetically determined and actively regulated by diverse inducers and inhibitors. One of these inducers, hyperphosphatemia, promotes vascul...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.644
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:To identify susceptibility genes for diabetic nephropathy, GeneChip Expression Analysis was employed to survey the gene expression profile of diabetic KK/Ta mouse kidneys. METHODS:Kidneys from three KK/Ta and two BALB/c mice at 20 weeks of age were dissected. Total RNA was extracted and labeled for hybridiz...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00312.x
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:In uremic patients with secondary hyperparathyroidism (2HPT), nodular hyperplasia of parathyroid gland shows a monoclonal pattern of cell proliferation, in which a decreased density of vitamin D receptor (VDR) also is demonstrated. The present study aimed at elucidating the mechanism of parathyroid cell prol...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid585.x
更新日期:2002-10-01 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::Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathologic...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1038/ki.2012.307
更新日期:2012-12-01 00:00:00