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Sökning: L773:0085 2538 > (2010-2014)

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1.
  • Abedini, Sadollah, et al. (författare)
  • Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients
  • 2010
  • Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 77:1, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.
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  • Bendz, Hans, et al. (författare)
  • Renal failure occurs in chronic lithium treatment but is uncommon.
  • 2010
  • Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 77, s. 219-224
  • Tidskriftsartikel (refereegranskat)abstract
    • We sought to establish the prevalence of lithium-induced end-stage renal disease in two regions of Sweden with 2.7 million inhabitants corresponding to about 30% of the Swedish population. Eighteen patients with lithium-induced end-stage renal disease were identified among the 3369 patients in the general lithium-treated population, representing a sixfold increase in prevalence compared with the general population for renal replacement therapy. All lithium-treated patients were older than 46 years at end-stage renal disease with a mean lithium treatment time of 23 years with ten patients having discontinued lithium treatment an average of 10 years before the start of renal replacement therapy. The prevalence of chronic kidney disease (defined as plasma creatinine over 150 mumol/l) in the general lithium-treated population was about 1.2% (excluding patients on renal replacement therapy). Compared with lithium-treated patients without renal failure, those with chronic kidney disease were older and most were men but, as groups, their mean serum lithium levels and psychiatric diagnoses did not differ. We found that end-stage renal disease is an uncommon but not rare consequence of long-term lithium treatment and is more prevalent than previously thought. Time on lithium was the only identified risk factor in this study, suggesting that regular monitoring of renal function in these patients is mandatory.Kidney International advance online publication, 25 November 2009; doi:10.1038/ki.2009.433.
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4.
  • Bienaime, Frank, et al. (författare)
  • Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome
  • 2010
  • Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 77:4, s. 339-349
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI. Their overall clinical outcome was unfavorable, as half died or developed end-stage renal disease after their first syndrome episode. Eight patients with CFI mutations carried at least one additional known genetic risk factor for aHUS, such as a mutation in MCP, CFH, C3 or CFB; a compound heterozygous second mutation in CFI; or mutations in both the MCP and CFH genes. Five patients exhibited homozygous deletion of the Factor H-related protein 1 (CFHR-1) gene. Ten patients with aHUS had one mutation in their CFI gene (Factor I-aHUS), resulting in a quantitative or functional Factor I deficiency. Patients with a complete deletion of the CFHR-1 gene had a significantly higher risk of a bad prognosis compared with those with one Factor I mutation as their unique vulnerability feature. Our results emphasize the necessity of genetic screening for all susceptibility factors in patients with aHUS. Kidney International (2010) 77, 339-349; doi: 10.1038/ki.2009.472; published online 16 December 2009
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  • Colom, Helena, et al. (författare)
  • Pharmacokinetic modeling of enterohepatic circulation of mycophenolic acid in renal transplant recipients.
  • 2014
  • Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 85:6, s. 1434-1443
  • Tidskriftsartikel (refereegranskat)abstract
    • Several factors contribute to mycophenolic acid (MPA) between-patient variability. Here we characterize the metabolic pathways of MPA and quantify the effect of combining genetic polymorphism of multidrug-resistant-associated protein-2, demographics, biochemical covariates, co-medication (cyclosporine (CsA) vs. macrolides), and renal function on MPA, 7-O-MPA-glucuronide (MPAG), and acyl-glucuronide (AcMPAG) disposition, in renal transplant recipients, after mycophenolate mofetil. Complete pharmacokinetic profiles from 56 patients (five occasions) were analyzed. Enterohepatic circulation was modeled by transport of MPAG to the absorption site. This transport significantly decreased with increasing CsA trough concentrations (CtroughCsA). MPAG and AcMPAG plasma clearances significantly decreased with renal function. No significant influence of multidrug-resistant-associated protein-2 C24T single-nucleotide polymorphism was found. The model adequately predicted the increase in MPAG/AcMPAG exposures in CsA and macrolide patients with decreased renal function. This resulted in higher MPA exposures in macrolide patients versus CsA patients, and increased MPA exposures with renal function from 25 to 10 ml/min, in macrolide patients, owing to enhanced MPAG enterohepatic circulation. Lower-percentage enterohepatic circulation occurred with higher CtroughCsA and renal function values. The lack of MPA protein-binding modeling did not permit evaluation of the impact of renal function and CtroughCsA on MPA exposures in CsA patients. Thus, dose tailoring of covariates is recommended for target MPA exposure.Kidney International advance online publication, 8 January 2014; doi:10.1038/ki.2013.517.
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