Abstract:
BACKGROUND:The new oral microemulsion formulation of cyclosporine (Neoral) possesses superior pharmacokinetics to the conventional formulation, Sandimmun (SIM), providing more complete and predictable absorption, and less pharmacokinetic variability. METHODS:The safety and tolerability of Neoral, together with the incidence of acute rejection episodes and graft survival, were compared to the conventional cyclosporine formulation, SIM, in a prospective, randomized, double-blind multicenter trial. A total of 167 patients who received a first or second cadaveric renal transplant in 21 participating centers in six countries were randomized equally to two treatment groups and followed for three months after transplantation. Outcomes were analyzed across treatment, center and regional groups. In addition, a nested pharmacokinetic study was performed in four of these centers throughout the period of follow-up. RESULTS:No difference was detected between the safety or tolerability of the two formulations. Kidney function and other laboratory parameters remained comparable in Neoral- and SIM-treated patients throughout the study. However, the number of patients experiencing acute rejection was significantly reduced for the Neoral group (44.2% vs. 60.5%; P = 0.044), and significantly fewer patients experienced multiple episodes of rejection (12.8% vs. 22.2%, P = 0.028). The proportion of patients free of rejection at three months was significantly higher in patients treated with Neoral than in those receiving SIM (Kaplan-Meier estimated probability of remaining rejection-free at 3 months = 55% for the Neoral group, compared with 39% for the SIM group, P = 0.046, log rank test). Similar results were obtained when acute rejection, graft loss and death were used as a combined endpoint (Kaplan-Meier estimated probability for Neoral group = 54%, compared with 38% for the SIM group, P = 0.047, log rank test). Comparison of results by center or regional groups did not show any significant treatment interaction. A nested pharmacokinetic evaluation (four centers; 28 subjects) showed that the bioavailability of cyclosporine from Neoral was significantly higher than from SIM at all assessment times. Specifically, at weeks 2, 4 to 6, and 12, dose-normalized AUC was 49%, 63% and 32% higher for Neoral. Dose-normalized peak cyclosporine blood concentrations and AUC stabilized by weeks 4 to 6 in patients receiving Neoral, whereas these values increased slowly in SIM-treated patients without reaching the levels achieved in the Neoral group. CONCLUSIONS:These results suggest that the superior pharmacokinetic characteristics of the microemulsion formulation of cyclosporine lead to more efficient immunosuppression during the first critical months after transplantation, without a deleterious impact on clinical safety.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Keown P,Niese Ddoi
10.1046/j.1523-1755.1998.00042.xsubject
Has Abstractpub_date
1998-09-01 00:00:00pages
938-44issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30712-2journal_volume
54pub_type
临床试验,杂志文章,多中心研究,随机对照试验abstract::Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001853
更新日期:2006-11-01 00:00:00
abstract::Progressive renal fibrosis is the final common pathway leading to renal failure irrespective of the initiating cause. Clinical studies of renal fibrosis found that prominent mast cell accumulation correlated with worse outcomes. Mast cells are pluripotent innate immune cells that synthesize and secrete profibrotic med...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.211
更新日期:2012-09-01 00:00:00
abstract::Unidirectional 32P-phosphate and 3H-mannitol fluxes were simultaneously measured, at two minutes intervals, in frog urinary bladders. The spontaneous or externally imposed transepithelial potential (PD) and short circuit current (SCC) were also recorded in most experiments. It was observed that: (1) Phosphate transfer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.9
更新日期:1988-01-01 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:BACKGROUND:Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. The chromosomal locus for MCKD2 was localized on chromosome 16p12. Within this chromosomal region...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00269.x
更新日期:2003-11-01 00:00:00
abstract::Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.201
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:There is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-l beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF) in bone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00835.x
更新日期:2003-03-01 00:00:00
abstract::VLDL receptor (VLDL-R) is a novel member of the LDL receptor gene family with distinct tissue distribution and function. It binds and internalizes VLDL particles and is primarily expressed in skeletal muscle, heart, brain and adipose tissue, which use fatty acids for energy production or storage. CRF is associated wit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.129
更新日期:1997-03-01 00:00:00
abstract::To evaluate the effect of continuous ambulatory peritoneal dialysis (CAPD) on the anemia of endstage renal disease, serial measurements of red cell mass and other hematological parameters were performed in 34 patients. Twenty-five patients were measured at the start and at 6 months (group 1), 13 at the start, at 6 and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.88
更新日期:1983-05-01 00:00:00
abstract:BACKGROUND:Macrophage (Mphi) infiltration may contribute to chronic renal injury. We therefore sought to examine the expression of genes associated with Mphi recruitment in the rat remnant kidney model. METHODS:Male Munich Wistar rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no treatment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00327.x
更新日期:2000-10-01 00:00:00
abstract::Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease heterogeneity and the lack of specificity of certain MHC typing techniques may have contributed to the lack of consistency in those studies. We therefore studie...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.37
更新日期:1995-01-01 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::Proteomics-based assays have substantially improved diagnostic accuracy in systemic amyloidosis and have led to the discovery of novel amyloidogenic proteins. The observation that human apolipoproteins are increasingly represented is intriguing and highlights the complex, and partially known, mutual effects of the mis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.05.029
更新日期:2016-09-01 00:00:00
abstract::Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.12.013
更新日期:2020-12-22 00:00:00
abstract:BACKGROUND:Nitric oxide (NO) has been shown to be a paracrine/autocrine regulator of proximal tubular transport. In this study, we investigated the effect of NO on the paracellular permeability of opossum kidney (OK) cells, a proximal tubule cell line that possesses a leaky paracellular pathway resembling that of the i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00465.x
更新日期:1999-06-01 00:00:00
abstract::From September 9 to October 3, 1994, five patients on maintenance hemodialysis in a dialysis unit in Tokyo contracted hepatitis B virus (HBV) infection successively, and four of them died of fulminant hepatitis. The unit treated 181 patients three times a week on eight shifts, and all five afflicted patients were on t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.499
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the alpha-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00691.x
更新日期:2002-12-01 00:00:00
abstract::Accumulating evidence indicates that asymptomatic hyperuricemia is involved in the development of hypertension and chronic kidney disease. A 2-hit model has been proposed to explain the role of urate in hypertension. The first hit entails activation of the renin-angiotensin system and inhibition of nitric oxide synthe...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2020.05.056
更新日期:2020-11-01 00:00:00
abstract::Chronic kidney disease (CKD) is usually associated with interstitial leukocytic cell infiltrates, which may contribute to disease progression by production of proinflammatory, proapoptotic, and profibrotic mediators. Recruiting leukocytes into the kidney involves local expression of chemotactic cytokines, that is, che...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000053
更新日期:2006-01-01 00:00:00
abstract::The effects of endogenous and exogenous glucocorticoids on renal active and prokallikrein levels (ng/mg protein) and in vivo kallikrein synthesis rate were studied in the conscious rat. Within two hours after low dose methylprednisolone (MP, 0.0125 to 0.05 mg/100 g body wt), active kallikrein and prokallikrein fell (2...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.188
更新日期:1990-08-01 00:00:00
abstract::Antibody responses to antigens are impaired in humans and animals with chronic renal failure (CRF), and parathyroid hormone (PTH) inhibits Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM)-induced antibody production by B cells from normal subjects. Since CRF is associated with secondary hyperparathyroidis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.286
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND:Estradiol suppresses the synthesis of type I collagen by murine mesangial cells. However, neither the alpha 1(I) nor the alpha 2(I) collagen gene contains an estrogen-response element. Because estradiol modulates the transcription of several genes that lack an estrogen-response element but contain a regulato...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00376.x
更新日期:1999-04-01 00:00:00
abstract::We report the stepwise application of the RIFLE classification in 155,624 admissions in the UK Intensive Care National Audit & Research Centre Case Mix Programme database. The assumptions required to define RIFLE and their relationship with renal replacement therapy (RRT) and ICU mortality were assessed. Previous repo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.70
更新日期:2015-08-01 00:00:00
abstract::Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 +/- 0.1 vs. 1.62 +/- 0.6 mg/deciliter, 17.0 +/- 10.3 vs. 257.6 +/- 13.4 mg/24 hr, and 16.6 +/- 4.4 vs. 39.2 +/- 11.7 ml/24 hr, resp...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.49
更新日期:1986-03-01 00:00:00
abstract::Tubular function studies have shown that nephrectomy leads to a sharp increase in potassium secretion by initial collecting tubules. The aim of this study was to examine the relationship between potassium transport and the cellular morphology of the distal nephron. Clearance and ultrastructural studies were conducted ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.58
更新日期:1985-04-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00245.x
更新日期:2005-04-01 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::Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.112
更新日期:2014-12-01 00:00:00
abstract::This very brief summary of the various possible contributions of PG to normal and abnormal renal function should highlight the problem of assigning a specific role to PG in overall renal physiology and pathophysiology. PG produced in specific segments of the nephron will affect specific functions occurring in this seg...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1986.13
更新日期:1986-01-01 00:00:00
abstract::Current practice recommends metabolic evaluation of patients who have formed multiple renal stones, but not those with one stone or temporally remote stones. This presumes that recentness and recurrence imply greater risk of new future stones. We hypothesize that number of stones reflects how long patients are permitt...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.224
更新日期:1994-06-01 00:00:00